RARE DISEASE
Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain-Barré syndrome
Synonyms: GBS, Guillain-Barré-Strohl syndrome
Synonyms: GBS, Guillain-Barré-Strohl syndrome
Synonyms: GBS, Guillain-Barré-Strohl syndrome
Drug discovery
11
drugs
With orphan designations
Overview
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide [2][5]. Characterized by ascending paralysis, sensory abnormalities, and autonomic dysfunction, it typically follows infections or vaccinations [5][16]. Diagnosis relies on clinical presentation, cerebrospinal fluid analysis, and nerve conduction studies [6][11]. First-line treatments include IV immunoglobulin (IVIG) and plasma exchange [3][8], with most patients achieving functional recovery despite potential long-term disability [1][16].
Categories: rare neurological diseases
Research Papers
1,580 drug discovery papers about Guillain-Barré syndrome, with 3 first-in-class and 36 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,580 drug discovery papers about Guillain-Barré syndrome, with 3 first-in-class and 36 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-31 | Pyruvate Kinase M2 Upregulation Is Associated With Guillain-Barré Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model.
This study aimed to investigate the potential involvement of pyruvate kinase M2 (PKM2) in the pathogenesis of Guillain-Barré syndrome (GBS). Mendelian randomization (MR) analysis was used to evaluate the causal association between PKM2 expression and GBS susceptibility, with mediation analysis performed to explore immune cell-mediated pathways. The association between PKM2 methylation and GBS risk was further examined using GoDMC mQTL data and GRT-qPCRWAS Data Hub profiling. To validate these findings experimentally, an experimental autoimmune neuritis (EAN) mouse model was established in male C57BL/6 mice (6-8 weeks) by immunization with P0180-199 peptide, with tissues collected at disease initiation (Day 8) and peak stage (Day 16). PKM2 expression dynamics, Th17/Treg (regulatory T cells) balance, and histopathological changes were assessed using, Western blot, immunohistochemistry, immunofluorescence, flow cytometry, and H&E/Luxol fast blue (LFB) staining. MR analysis revealed that elevated PKM2 expression in the tibial nerve was significantly associated with an increased risk of GBS (OR: 1.75-6.14, p < 0.05). In the EAN model, PKM2 expression in the sciatic nerve exhibited a time-dependent increase (p < 0.01), primarily localized to inflammatory infiltrates. Mechanistic studies demonstrated that PKM2 upregulation in CD4+ T cells was associated with promoted Th17 differentiation, as evidenced by the upregulation of IL-17a and RORγt (p < 0.05), concomitant with a reduction in Treg cells (p < 0.01). To further elucidate the upstream epigenetic regulation, the association between PKM2 methylation and GBS risk was investigated using GoDMC mQTL data. Among the four selected methylation sites, two-sample MR analyses indicated that cg24327132 were positively associated with GBS risk (p < 0.05). Furthermore, analysis of the GWAS Data Hub revealed that cg24327132 appeared to be preferentially hypomethylated in adaptive immune cells including regulatory T cells, CD4+ T cells, and B cells (Beta ≈ 0-0.05), visually distinct from innate immune populations (Beta ≈ 0.10-0.20), suggesting that perturbation of this hypomethylated state may dysregulate PKM2 expression and contribute to GBS susceptibility. PKM2 upregulation is associated with GBS risk and immune dysfunction. PKM2 methylation may represent a key regulatory mechanism underlying this association. PKM2 may represent a mechanism target warranting further therapeutic investigation.
2026-06-25 | Pediatric GBS-myelitis overlap syndrome: Severe phenotype, treatment response, and neurological outcomes.
To characterize the clinical features, treatment responses, and outcomes of pediatric patients with Guillain-Barré syndrome (GBS) and concurrent myelitis. Clinical and auxiliary data from 22 pediatric patients (5 from local hospital and 17 by reviewing the previous literatures) with GBS and myelitis were analyzed. Parameters included demographics, neuroimaging, cerebrospinal fluid (CSF) findings, immunotherapy regimens, and outcomes stratified by the Hughes Functional Grading Scale. In this pediatric cohort (median age: 11.0 years; male-to-female ratio ≈1:1), GBS with concurrent myelitis manifested with flaccid paralysis in 95.5% of cases, including quadriplegia (59.1%), accompanied by diminished deep tendon reflexes (90.9%). Sensory disturbances were documented in 77.3% of patients, while autonomic dysfunction featured urinary impairment (68.2%) and respiratory failure requiring ventilation (52.6%). Neurodiagnostic findings universally demonstrated long-segment spinal cord lesions (>5 vertebral segments) on MRI and albuminocytological dissociation in CSF analysis. First-line immunotherapy comprised intravenous immunoglobulin (IVIG) and corticosteroids. Severity stratification identified a severe group (Hughes Grade ≥ 3; n = 13) characterized by: tetraplegia (92.3%), respiratory failure (69.2%), extensive spinal cord edema (84.6%), prolonged hospitalization (median: 6.0 weeks), higher residual sequelae (69.2%). The majority of patients in this group (92.3%) necessitated combination therapy with IVIG and corticosteroids. Pediatric GBS with myelitis frequently presents with severe neurological involvement. Although combination immunotherapy demonstrates efficacy, the severe subgroup shows significant residual morbidity. Early aggressive intervention is warranted to mitigate long-term disability.
2026-06-17 | [Guillain-Barré syndrome following allogeneic hematopoietic stem cell transplantation in a pediatric patient: a case report and literature review].
A 10-year-old girl diagnosed with hyper-IgE syndrome for more than six years developed dizziness and symmetrical progressive limb weakness one week prior to hospital admission, occurring 4 months after allogeneic hematopoietic stem cell transplantation. On post-transplant day 121, dizziness and progressive, symmetric limb weakness appeared. Cerebrospinal fluid analysis revealed albuminocytologic dissociation. Electromyography confirmed multiple peripheral nerve lesions, consistent with the diagnosis of Guillain-Barré syndrome. Intravenous immunoglobulin therapy showed limited efficacy, whereas corticosteroid therapy produced significant clinical improvement. Neurological symptoms fully resolved after treatment; however, severe chronic graft-versus-host disease occurred subsequently. Based on this case, related literature was reviewed and summarized to provide references for early diagnosis, mechanistic investigation, and treatment options.
2026-04-06 | Qualitative evaluation of pharmacological strategy for connective tissue diseases with Guillain-Barré syndrome: a systematic review.
To systematically evaluate the pharmacological management of Guillain-Barré syndrome occurring in the context of connective tissue diseases (CTD-GBS) and to investigate the relative efficacy of different treatment regimens on neurological outcomes. Case reports and series regarding CTD-GBS were systematically retrieved from PubMed, Embase, and Web of Science databases. A Generalized Linear Mixed Model (GLMM) was utilized to assess independent associations between treatment regimens and neurological improvement, adjusting for key covariates including mechanical ventilation (as a baseline severity marker) and the year of publication. A total of 105 CTD-GBS patients were identified, with systemic lupus erythematosus (SLE) being the most prevalent subtype (n=73). Multivariable GLMM analysis suggested that, compared to intravenous immunoglobulin (IVIG) monotherapy, intensive combination regimens specifically glucocorticoids combined immunosuppressants (GC + IS) demonstrated a potential association with higher odds of clinical improvement (adjusted Odds Ratio [aOR] = 30.90; 95% CI: 6.58-145.00; p < 0.001). Mechanical ventilation was identified as an independent negative predictor of recovery (aOR = 0.43; p = 0.037), while the year of publication did not significantly influence outcomes (p = 0.344). Descriptive analysis within the SLE-GBS subgroup corroborated these trends, with the GC + IS regimen achieving a clinical improvement rate of 88.9%. Preliminary evidence suggests that intensive immunosuppressive combination therapy, notably GC + IS, may offer advantages over traditional IVIG monotherapy in improving short-term neurological outcomes for CTD-GBS patients. However, given the reliance on retrospective case-based evidence and the potential for confounding by indication, these findings should be interpreted as hypothesis-generating clinical clues rather than definitive guidelines. Future large-scale, prospective studies utilizing standardized functional assessment scales are urgently required to validate these preliminary observations.
2026-04-03 | Methylprednisolone as an adjunct to intravenous immunoglobulin in pediatric Guillain-Barré syndrome: a prospective comparative study.
Guillain–Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children. Intravenous immunoglobulin (IVIG) is considered the standard therapy; however, the potential benefit of adjunctive corticosteroids remains uncertain.This study aimed to explore whether the addition of short-course intravenous methylprednisolone to IVIG may accelerate recovery and alleviate neuropathic pain in pediatric patients with GBS. A prospective, comparative study was conducted at Al-Azhar University Hospitals, enrolling 28 pediatric patients with clinically and electrophysiologically confirmed GBS. Participants were randomized into two equal groups: Group A received IVIG alone (1 g/kg/day for two days), while Group B received IVIG combined with pulse-dose methylprednisolone (30 mg/kg/day for five days). Clinical outcomes including time to initial improvement, unaided ambulation, Hughes Disability Score, neuropathic pain, and adverse events were assessed over a six-month follow-up period. Baseline characteristics were comparable between groups. The combination therapy group demonstrated faster initial improvement (median 3 vs. 4.5 days), earlier independent ambulation (21 vs. 28 days), and modest improvement in Hughes score at three months (median 0 vs. 1, p = 0.016), though clinical significance is limited. Neuropathic pain resolved completely in the steroid group but persisted in 57.1% of the IVIG-only group (p = 0.002). By six months, nearly all patients achieved complete recovery. Adverse events in the combination group were limited to mild weight gain and increased appetite. Short-course methylprednisolone as an adjunct to IVIG may provide early benefits, particularly in pain resolution, without major safety concerns. These findings are preliminary and hypothesis-generating, requiring confirmation in larger multicenter trials. These findings highlight a feasible and safe strategy that could be particularly valuable in resource-limited healthcare settings, though confirmation in larger multicenter trials is warranted.
cell therapies
2026-07-31 | Case Report: Guillain-Barré syndrome mimicking acute brainstem stroke with severe autonomic dysfunction-complete recovery after early plasma exchange.
Acute onset of bilateral ptosis, bulbar palsy, and quadriparesis typically raises suspicion for brainstem infarction. However, when neuroimaging is unrevealing, immune-mediated neuropathies such as Guillain-Barré syndrome (GBS) should be considered. This case highlights the diagnostic challenge and therapeutic response in a seronegative, rapidly progressive GBS variant with severe autonomic involvement. We report a 57-year-old previously healthy man who presented with acute right-sided weakness and dysarthria, progressing over 36 hours to bilateral ptosis, complete ophthalmoplegia, dilated pupils, bulbar palsy, flaccid quadriparesis, urinary retention, and paralytic ileus. Initial brain MRI-DWI was negative. CSF showed no albuminocytologic dissociation. Anti-ganglioside antibodies and neuromuscular junction antibodies were negative. Electromyography revealed motor-predominant polyneuropathy with sympathetic skin response abnormalities. A diagnosis of atypical GBS with severe autonomic involvement was made. Plasma exchange was initiated at 40 hours after onset, followed by a second session on day 5. The patient improved dramatically, walked independently by day 8, was discharged on day 15, and achieved complete recovery at 1 month. This case demonstrates that GBS can present as an acute brainstem stroke mimic with severe ileus and urinary retention, even in the absence of CSF abnormalities or detectable autoantibodies. Early plasma exchange may result in complete neurological recovery. Therefore, clinicians should maintain a high clinical suspicion for immune-mediated neuropathies in patients presenting with rapidly progressive stroke mimics accompanied by autonomic dysfunction.
2026-07-30 | Robot-assisted gait training using a robotic exoskeleton during inpatient rehabilitation in acute Guillain-Barré Syndrome.
A woman in her early 60s with acute Guillain-Barré syndrome (GBS) developed rapidly progressive tetraparesis and respiratory failure requiring non-invasive ventilation. Following intravenous immunoglobulin and medical stabilisation, she entered inpatient rehabilitation with severe weakness, poor truncal control and inability to ambulate. Despite intensive conventional therapy, early gait training was limited. Exoskeleton-based robot-assisted gait training (RAGT) using the Hybrid Assistive Limb (HAL; Cyberdyne Inc, Tsukuba, Japan) was introduced during inpatient rehabilitation as an adjunct to standard therapy. The patient completed 10 HAL sessions over a 15-day period without adverse events. During this time, progressive improvements in ambulatory distance and functional independence were observed. By completion of HAL training, she was able to ambulate 50 m with a walking stick and minimal assistance. She subsequently continued conventional rehabilitation and achieved independent ambulation by discharge. This case suggests that HAL-based RAGT may be a feasible adjunct to inpatient rehabilitation in medically stable patients with acute GBS. The intervention was well tolerated in this patient. Further studies are required to establish patient-selection criteria, optimal timing and the effectiveness of exoskeleton-assisted gait training in GBS.
2026-07-11 | Impact of Gut Microbiota Dysbiosis in Treatment Outcomes of Guillain-Barré Syndrome.
The gut-microbiota plays a significant role in neuro-autoimmune diseases, like Guillain-Barré syndrome (GBS), a post-infectious disorder of the peripheral nervous system (PNS). By altering host immunity, gut dysbiosis may impact the standard therapeutic efficacy of intravenous immunoglobulin (IVIg) and plasma exchange (PE) and thereby, disease progression in GBS. In this study, we investigated the impact of gut-microbiota diversity on therapeutic outcomes of IVIg and PE in patients with GBS. We enrolled 60 patients with GBS categorized into three treatment groups: IVIg-treated, PE, and supportive-care along with 60 age-sex-matched healthy controls from Bangladesh. Fecal microbial DNA was extracted at different timepoints and sequenced. Clinical and sequenced data were analyzed using the Qiime2-Dada2 pipeline. Gut-microbial diversity significantly differed in patients with GBS before and after treatment (Shannon: p = 0.037; Evenness: p = 0.012), particularly in IVIg-treated patients, showing significant changes after 6-month treatment (Shannon: p = 0.034; Evenness: p = 0.011). Beta diversity indicated microbiota restoration in IVIg-treated patients toward a healthy state after treatment (p ≤ 0.001). Phylum Actinobacteriota (p = 0.026), genera Bifidobacterium (p = 0.006), and Enterococcus (p ≤ 0.0001) were relatively abundant in severe patients. Mechanically ventilated patients showed significant gut-microbial diversity (Unweighted-UniFrac; p ≤ 0.001). Biomarker analysis identified a higher abundance of Eubacterium, Bacteroides, Escherichia-Shigella, and Actinomyces in GBS patients. Our exploratory study indicates that gut microbiota dysbiosis is associated with GBS severity and IVIg-treatment outcomes. IVIg-treatment promoted partial restoration of microbial diversity, suggesting a potential immunomodulatory effect mediated through the microbiota. Further studies using meta-transcriptomics are warranted to define functional consequences of microbial shifts in treatment responses of GBS.
2026-06-22 | Exploring the Feasibility and Patient Acceptance of RAGT for Overground Ambulation in Adults With Guillain-Barré Syndrome: A Scoping Review.
To review the current literature on the feasibility as well as weaknesses and strengths of robot-assisted gait training (RAGT) in the rehabilitation of gait in adult patients with Guillain-Barré syndrome (GBS). This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Scoping Reviews guidelines. A systematic search between November 2024 and May 2025 of PubMed, Cochrane Library, Embase, Canadian Agency for Drugs and Technologies in Health (CADTH) Grey Matters, and citation mining was performed to evaluate for relevant studies. All studies involving the use of RAGT in adults (≥18y) diagnosed with acute inflammatory demyelinating polyneuropathy or GBS were included. Eligible study designs comprised case reports, case series, feasibility studies, and randomized controlled trials. The search yielded 11 potentially relevant articles. Study selection was conducted in 2 stages: title and abstract screening followed by full-text review. Discrepancies between the 2 independent reviewers were resolved through discussion until consensus was achieved. Four studies met the inclusion criteria, comprising 2 case reports, 1 mixed-methods feasibility study, and 1 cross-sectional study, with a total of 19 participants. Across studies, RAGT was generally reported to be feasible, well tolerated, and acceptable to patients, with no major safety concerns. Reported benefits included the ability to initiate overground ambulation, high-intensity repetitive gait practice, and reduced physical burden on therapists. Patient acceptance was supported by positive user experiences, adherence to training sessions, and completion of prescribed protocols, although outcome measures and reporting were inconsistent. The current evidence base for RAGT in adults with GBS is limited but suggests that it is a feasible and acceptable adjunct to conventional rehabilitation. Although functional improvements were reported, conclusions regarding effectiveness remain constrained by small sample sizes and study heterogeneity. Further prospective and methodologically robust studies are needed to better characterize feasibility, patient experience, and implementation considerations of RAGT in this population.
2026-05-11 | Microbiota and Guillain-Barré syndrome: role of microbial metabolites, biomarkers, and emerging therapeutic strategies.
Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy that follows infection and is characterized by immune-mediated demyelination or axonal injury of the peripheral nervous system. While established triggers such as Campylobacter jejuni are well recognized, increasing evidence implicates the gut microbiota as a key modulator of immune responses relevant to GBS pathogenesis. The intestinal microbiota produces a diverse array of bioactive metabolites, including short-chain fatty acids (SCFAs), tryptophan-derived indoles, and neurotransmitter-like molecules, which influence immune tolerance, gut barrier integrity, and neuroinflammatory signaling. SCFAs, particularly butyrate, exert anti-inflammatory effects and support epithelial and blood-nerve barrier function. Microbial tryptophan metabolites regulate astrocyte and microglial activity via aryl hydrocarbon receptor (AHR) signaling, thereby restraining central and peripheral neuroinflammation. In contrast, dysbiosis-associated metabolites such as lipopolysaccharide (LPS) may enhance systemic inflammation, disrupt immune tolerance, and promote autoantibody production through mechanisms including molecular mimicry. Studies suggest that specific microbial taxa and metabolite signatures may serve as diagnostic or prognostic biomarkers in GBS, offering insights into disease susceptibility and progression. Microbiota-targeted therapeutic strategies are emerging as promising adjuncts to immunotherapy. Probiotics and prebiotics may restore beneficial microbial communities and rebalance immunoregulatory metabolite production, while host-directed metabolic interventions such as creatine supplementation may further support mitochondrial function, immunometabolic homeostasis, and neuroprotection. Fecal microbiota transplantation (FMT), though still experimental in GBS, has shown benefit in related neuroinflammatory disorders by reestablishing eubiosis and dampening immune activation. Future studies integrating metagenomic, metabolomic, and immunologic profiling in well-characterized GBS cohorts are essential to validate these findings and advance personalized microbiota-based interventions.
antibodies
2026-08-03 | Corrigendum to "Elsberg Syndrome with Albuminocytologic Dissociation - A Guillain-Barré Syndrome Mimic or Guillain-Barré Syndrome Variant?".
[This corrects the article DOI: 10.1177/19418744241233621.].
2026-07-29 | Clinical spectrum and prognostic features of patients seropositive for anti-GD1a antibody.
Anti-GD1a antibodies are associated with a range of immune-mediated neuropathies, particularly acute motor axonal neuropathy (AMAN) and other Guillain-Barré syndrome (GBS) variants. However, their full clinical spectrum and prognostic significance remain unclear due to limited systematic studies. Here, we investigated the clinical phenotypes, serological profiles, cerebrospinal fluid (CSF) characteristic, and therapeutic outcomes associated with anti-GD1a antibodies. The clinical, paraclinical and therapeutic data were retrospectively collected and analyzed from 19 Chinese patients who tested positive for anti-GD1a antibodies. The mean age at onset in this cohort was 50.6 years. Among the 19 patients, 14 (74%) presented with acute syndromes. The remaining five patients (26%) exhibited features consistent with chronic neuropathies. Common manifestations included absent tendon reflexes (84%), limb weakness (84%), sensory impairment (58%), and cranial nerve involvement (53%). Isolated anti-GD1a antibody positivity was observed in only 5 patients, while others had co-existing antiganglioside antibodies, most commonly anti-GQ1b, and anti-GM1. Electrophysiological studies revealed axonal and demyelinating neuropathic patterns. Patients with cranial nerve involvement and albuminocytologic dissociation were associated with higher modified Erasmus GBS Outcome Score (mEGOS). Immunotherapy was effective in acute cases, with 57% achieving complete recovery at 6-month follow-up. Patients seropositive for anti-GD1a antibody exhibits significant clinical and electrophysiological heterogeneity and frequently coexists with other antiganglioside antibodies. Acute presentations generally respond well to immunotherapy, while chronic cases require individualized management.
2026-07-23 | Neurological Manifestations of Mycoplasma pneumoniae Infection in Hospitalized Adults During the 2023-2024 French Epidemic, Clinical Characterization and Comparative Outcomes: A Multicenter Study.
Mycoplasma pneumoniae (MP) primarily causes respiratory infections but can lead to neurological manifestations. This study aimed to characterize these manifestations in adults during an epidemic. The national MYCADO cohort included 1309 adults hospitalized with MP infection during the 2023-2024 French epidemic. An ancillary study identified and described MP-related central (CNS) and peripheral (PNS) nervous system manifestations. Data were retrospectively extracted from medical records, with clinical follow-up up to 3 months after discharge. Twenty-eight patients with neurological manifestations attributable to MP were identified (2.1% of the cohort). Of these, 19 affected the CNS, including encephalitis (n = 8), myelitis (n = 3), encephalo-myelitis (n = 2), isolated meningitis (n = 6), and cerebral vasculitis (n = 1). Nine involved the PNS: Guillain-Barré syndrome (n = 6), peripheral polyneuropathy (n = 2), and multifocal neuropathy (n = 1). The median age (interquartile range) was 35 years (29-49) years; 60.7% were men. Neurological symptoms appeared a median of 7 days after MP infection onset. Nearly half (46.4%, n = 13) required intensive care; neurological failure was the leading cause of intensive care unit transfer (12/13, 92.3%). Compared with MP patients without neurological manifestations, those with neurological involvement had longer hospital stays (13 vs 9 days; P < .001), more frequent invasive mechanical ventilation (35.7% vs 4.2%; P < .001), and more rehabilitation transfers (42.8% vs 4.3%; P < .001). At discharge, neurological sequelae were present in 47.3% of CNS patients and all Guillain-Barré syndrome (GBS) patients. At 3 months, sequelae persisted in 36.8% of CNS patients and all GBS patients. In adults, MP infection causes rare but diverse and frequently severe neurological manifestations that worsen clinical course and result in long-term disability.
2026-07-17 | Clinical outcomes and safety of efgartigimod in Guillain-Barré syndrome: a retrospective observation study.
Guillain-Barré syndrome (GBS) is a severe acute autoimmune neuropathy with limited established therapeutic options. Efgartigimod, a human IgG antibody Fc fragment, can increase IgG degradation, which thus may be a promising therapeutic medicine for GBS. The aims of this study were to evaluate the clinical effectiveness and safety of efgartigimod in GBS patients. A retrospective study was conducted on GBS patients at the first affiliated hospital of Zhengzhou university and Nanyang central hospital from February 2024 to June 2025. The medical records of patients received IVIg, efgartigimod, or IVIg sequential efgartigimod (ISE) were reviewed. Disease severity was evaluated using GBS disability score (GBS-DS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score at baseline, week1, week2, week3, week4, and the final follow-up. The primary outcome was the proportion of good improvement, defined as a reduction of at least 2 points in the GBS-DS score compared to the baseline. All adverse events occurred during the treatment period were documented. 52 patients were enrolled and received IVIg (n=20), efgartigimod (n=16), or ISE (n=16). Good improvement was higher in the efgartigimod group than IVIg group both at week 2 (37.5% vs. 0%, p<0.01) and the final visit (81.3% vs. 40.0%, p=0.02). Throughout follow-up, the proportion with GBS-DS ≤1 in the efgartigimod group was consistently higher compared to the other two groups. Although not statistically significant, the mean time to reach GBS-DS ≤1 was shorter in the efgartigimod group (2.6± 1.2 weeks) compared to the IVIg (3.1 ± 1.1 weeks), In the ISE group, the average time to achieve GBS-DS ≤ 1 was 2.8 ± 1.2 weeks. Regarding safety, the incidence of treatment-related adverse events (TEAEs) was lower in the efgartigimod group18.8% (3/16) than in the IVIg50.0% (10/20) and ISE 43.8% (7/16) groups. Based on the preliminary finding, the retrospective real-world data suggesting a potential signal of benefit for efgartigimod in GBS, with no new safety concerns identified. However, this study cannot establish comparative efficacy given the methodological limitations, and large-scale well-controlled head-to-head trials remain imperative.
2026-07-15 | A Large Community Outbreak of Guillain-Barré Syndrome in Pune City, India, 2025.
Guillain-Barré syndrome (GBS) is a rare and potentially fatal immune-mediated disorder. During a large community outbreak in Pune City, India, investigations of GBS cases were conducted to identify the causes of antecedent or concurrent infections using serological and molecular methods. Water and poultry samples were also tested to determine the source of infection. From January to March 2025, 230 GBS cases, including 12 deaths (case fatality ratio 5.2%), were investigated. The cases were concentrated in Southwest Pune. All age groups were affected, with a male-to-female ratio of 2.2:1. Antecedent illness was reported in 147 (63.9%) cases, primarily diarrhea (37%). Among 193 cases, 108 (56%) were linked to infectious agents. Campylobacter jejuni (C. jejuni) infection was confirmed in 72 (48.7%) of 148 cases. Norovirus was confirmed in 40 (22.2%) of 180 cases, either as a coinfection (n = 19) or alone (n = 21). Water contamination was detected, with positive results for Campylobacter (n = 1/208) and norovirus (n = 8/208). Among 66 fecal samples from poultry, Campylobacter and norovirus were detected in 24 and five samples, respectively. No evidence of toxins was found in the nine water samples tested representatively. A significant GBS outbreak occurred in Pune City in early 2025, preceded by an acute diarrhea outbreak. A mixed etiology of the GBS outbreak was confirmed, with C. jejuni the leading cause in nearly half of the cases. Norovirus infection was also identified in more than one-fifth of the cases. Water contamination by both agents was detected, along with a possible link to poultry as a source of infection.
proteins
2026-06-12 | A recombinant IgG1 Fc-domain protein ameliorates inflammatory demyelinating peripheral neuropathy.
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated inflammatory neuropathies characterized by T cell- and/or autoantibody-driven injury to peripheral nerves. Although intravenous immunoglobulin (IVIg) is effective in both conditions, its use is limited by high dosing requirements, supply constraints, and manufacturing complexity. NVG-2089 is a recombinant IgG1 Fc-domain protein engineered to selectively agonize type II Fc receptors, promoting anti-inflammatory signaling through expansion of regulatory T cells (Tregs) and upregulation of the inhibitory Fcγ receptor FcγRIIB. Its efficacy in immune complex-mediated disease and T cell-driven neuroinflammation prompted evaluation of its therapeutic potential in an animal model of inflammatory demyelinating neuropathy. We conducted a randomized, blinded preclinical study in the spontaneous autoimmune peripheral polyneuropathy model, a well-established murine model of inflammatory demyelinating neuropathy. Animals were treated with NVG-2089, high-dose IVIg, or vehicle. Outcomes included behavioral performance, nerve electrophysiology, peripheral nerve morphometrics, immunohistochemistry, and flow cytometric immunophenotyping. Both NVG-2089 and IVIg stabilized motor and sensory performance, preserved compound muscle action potential (CMAP) amplitudes, and attenuated demyelination-associated prolongation of distal latency and CMAP duration. Morphometric analyses demonstrated preservation of myelinated fiber density and normalization of g-ratio distributions in both treatment groups. Immunophenotyping indicated an expansion of functionally activated CD25+CD39+ Tregs in the spleen, along with increased FcγRIIB expression on B cells, monocytes, and dendritic cells across systemic and nerve-associated compartments, consistent with engagement of shared anti-inflammatory pathways. NVG-2089 demonstrated robust neuroprotective efficacy comparable to IVIg while requiring a substantially lower protein dose. These findings support NVG-2089 as a promising, dose-efficient alternative to IVIg for the treatment of inflammatory demyelinating neuropathies, including GBS and CIDP.
2026-05-08 | Varicella-zoster virus infection triggering GD3 antibody-positive variant Guillain-Barré syndrome: a case report and literature review.
Bilateral facial palsy variant Guillain-Barré syndrome (GBS) is a distinct clinical subtype. As an acute immune-mediated polyradiculoneuropathy often triggered by infections, varicella-zoster virus (VZV) is a rare yet significant precipitating factor for this variant. Anti-ganglioside antibodies, particularly anti-GD3, are involved in the pathogenesis of GBS, but their significance in VZV-associated bilateral facial palsy subtype remains incompletely elucidated. We report a 46-year-old female who developed acute bilateral facial palsy and limb sensory deficits following VZV infection. Serum anti-ganglioside testing confirmed GD3 IgG positivity, and cerebrospinal fluid analysis revealed albuminocytological dissociation. Nerve conduction studies supported a demyelinating polyneuropathy, and the patient showed significant improvement after intravenous immunoglobulin therapy. This case suggests that VZV may act as a potential trigger for GD3 antibody-positive variant GBS. Early immunotherapy may improve outcomes, emphasizing the need for systematic antibody testing in atypical presentations of this variant GBS. Further studies are required to clarify the pathophysiological role of GD3 antibodies in VZV-associated variant GBS.
2025-11-05 | Diagnostic and therapeutic potential of resolvin D1 in Guillain-Barré syndrome.
Most neuroimmune diseases are incurable and require lifelong immunotherapy, whereas Guillain-Barré syndrome (GBS), a peripheral nervous system autoimmune disorder, has a relatively favorable prognosis. Investigating the molecular disparities underlying recovery between GBS and other neuroimmune diseases may facilitate the development of innovative therapeutic strategies. This study explored the diagnostic and therapeutic potential of resolvin D1 (RvD1), a specialized pro-resolving mediator that promotes inflammation resolution and tissue regeneration, in GBS and its animal model experimental autoimmune neuritis (EAN). Serum RvD1 levels were measured in 218 participants from two cohorts, including healthy controls (HCs), GBS patients, and those with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or stroke. The diagnostic accuracy was evaluated via the area under the receiver operating characteristic (ROC) curve (AUC). RvD1 was administered to EAN and experimental autoimmune encephalomyelitis (EAE, an MS animal model) to assess its therapeutic efficacy. Serum RvD1 was elevated in GBS patients, demonstrating high diagnostic accuracy in differentiating GBS patients from HCs (cohort 1: AUC 0.72; cohort 2: AUC 0.93), MS/NMOSD patients (cohort 1: AUC 0.83), and stroke patients (cohort 1: AUC 0.68). The RvD1 level continued to increase as GBS progressed and was positively correlated with disease severity, ventilator dependence, and axonal neuropathy. In EAN, RvD1 and its synthetase/receptor were upregulated in serum, spleen, and sciatic nerve, exhibiting tissue-specific inflammation resolution patterns across disease phases. RvD1 treatment promoted inflammation resolution in EAN, as evidenced by attenuated disease severity and autoimmune responses, with its therapeutic effect was translatable to EAE. RvD1 may serve as a biomarker for both diagnosing GBS and monitoring disease severity. It represents a potential immunotherapeutic agent for GBS and other neuroimmune disorders. Elucidating the molecules associated with recovery in patients with GBS may facilitate the discovery of novel therapeutic strategies for neuroimmune disorders.
2025-10-14 | Exacerbation of demyelinating polyneuropathy after adoptive cell therapy with tumour-infiltrating lymphocytes by metastatic melanoma.
Adoptive cell therapy (ACT) with tumour-infiltrating lymphocytes (TIL) is an effective personalised immunotherapy for patients with advanced pretreated melanoma. For TIL-ACT, tumour-specific T cells are expanded from excised tumour samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous tumour-infiltrating lymphocytes are reinfused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Thereafter, activation of tumour-infiltrating lymphocytes in the patient is supported by the administration of high-dose IL-2. Although effective, there is a need for enhancement of TIL-ACT in terms of effectiveness and toxicity. Most of the toxicity in this multistep, complex treatment regimen is due to the preparative chemotherapy and high-dose IL-2 treatment. At University Hospital Basel, we are currently evaluating an experimental approach of TIL-ACT in which we replace high-dose IL-2 by in vivo tumour-infiltrating lymphocyte activation with ANV419, a novel antibody-cytokine fusion protein consisting of IL-2 fused to an anti-IL-2 monoclonal antibody, in an ongoing phase I trial (BaseTIL-03M). The primary endpoint of the study is safety. We herein describe the case of a patient included in the BaseTIL-03M trial with chronic inflammatory demyelinating polyneuropathy who received TIL-ACT with ANV419 and developed an acute polyneuropathy of Guillain-Barré syndrome.
2025-08-24 | Design of Hyperglycosylated Zika Virus E Proteins that Focus Antibody Recognition on the Complex E Dimer Epitope.
Zika virus (ZIKV) and dengue virus serotypes 1-4 (DENV1-4) are flaviviruses spread by Aedes mosquitoes. ZIKV infection can cause Guillain-Barré syndrome and microcephaly, while severe dengue can lead to hemorrhagic fever and death. DENV infection of ZIKV-immune individuals is linked to severe clinical outcomes due to antibody-dependent enhancement (ADE) of infection. Thus, the development of broadly protective vaccines is an important objective. We focus on the E dimer epitope (EDE) of ZIKV, which is targeted by broadly neutralizing antibodies that protect against ZIKV and DENV1-4. We engineered ZIKV E dimer variants containing non-native asparagine-linked glycosylation sites to block antibody responses to regions outside the EDE using a structure-based iterative design approach. One candidate, SC30m53, bound EDE mAbs but not other mAbs and induced a potently neutralizing response against ZIKV and moderately cross-neutralizing responses against DENV1-3 in mice. These findings suggest that hyperglycosylation provides a promising approach to focusing the immune response on key epitopes.
other
2026-07-17 | COVID-19 mRNA Vaccination Reduces Guillain-Barré Syndrome Risk: Evidence from a Large Longitudinal Cohort Study.
The association between COVID-19 vaccination and Guillain-Barré syndrome (GBS) has been previously investigated with inconsistent results, largely due to limited data and lack of concurrent controls. To address this problem, a large longitudinal cohort study was conducted using National COVID Cohort Collaborative (N3C) data. While COVID-19 infection was associated with increased GBS occurrence, COVID-19 vaccination was associated with significantly reduced GBS risk relative to unexposed (unvaccinated and uninfected) control, corresponding to a 61% lower 30-day risk (incidence risk ratio: IRR = 0.39, P < 0.01), consistent with multivariable Cox regression showing a similar reduction (adjusted hazard ratio: aHR = 0.41, P < 0.01). This protective association was observed only among recipients of mRNA vaccines (BNT162b2: IRR = 0.38, P < 0.01; mRNA-1273: IRR = 0.24, P < 0.01), but not among recipients of adenoviral-vector vaccines (IRR = 1.38, P > 0.05). Prior COVID-19 vaccination also reduced infection-associated GBS risk. Additional factors associated with GBS risk included sex, vaccine dose, and pre-existing comorbidities such as stroke, neurological disorders, and autoimmune diseases. Overall, our N3C large-scale study provides evidence that COVID-19 mRNA vaccination reduces GBS risk, supporting the safety profile of mRNA vaccines and warranting further mechanistic investigation.
2026-04-01 | The EGR1/ZFP36 axis governs glycosphingolipid metabolic reprogramming in monocyte-derived macrophages in guillain-barré syndrome.
Guillain-Barré syndrome (GBS) is an immune-mediated demyelinating disorder of peripheral nerves with an unclear pathogenesis. This study integrated GBS clinical single-cell data with EAN model transcriptome data, establishing in vivo and in vitro experimental systems to reveal, for the first time, a novel mechanism involving EGR1-ZFP36 and its mediated metabolic reprogramming in GBS pathogenesis. Findings indicated that the transcription factor EGR1 and its predicted target gene ZFP36 were downregulated in both GBS patients and EAN rats. Molecular interaction validation confirmed that EGR1 directly bound to and activated the transcription of ZFP36. Transcriptomic and metabolomic analyses revealed that the EGR1/ZFP36 axis specifically drove macrophage reprogramming toward a glycosphingolipid metabolism-active state. Functionally, EGR1 overexpression promoted the expression of key glycosphingolipid metabolism genes (HEXA, HEXB) by upregulating ZFP36, thereby facilitating polarization toward the anti-inflammatory M2 phenotype. Animal experiments further demonstrated that EGR1 overexpression improved motor function and ameliorated myelin damage in the EAN model, with this protective effect being mediated by ZFP36. Collectively, this study reveals that EGR1 drives glycosphingolipid metabolic reprogramming in monocyte-derived macrophages by transcriptionally activating ZFP36, thereby regulating cellular polarization and participating in the demyelination process of GBS. This discovery not only provides a novel perspective on understanding the immunometabolic mechanisms of GBS but also lays a theoretical foundation for potential therapeutic strategies targeting the EGR1-ZFP36-glycosphingolipid metabolism axis.
2025-12-30 | A Review of Cutaneous Viral Infections and Their Potential Role in Neurologic Diseases.
Background: Cutaneous viral infections, defined as viral pathogens that either primarily affect the skin (e.g., herpesviruses, enteroviruses) or frequently produce dermatologic manifestations despite systemic tropism (e.g., HIV, SARS-CoV-2), can trigger systemic inflammatory and neurotropic responses that extend their impact to the nervous system. A growing body of evidence suggests that viruses with dermatologic manifestations may play a significant role in the pathogenesis of neurologic disorders. Summary: Although individual viruses have been studied in isolation, the skin-brain axis in viral infections remains incompletely characterized. This review synthesizes existing knowledge and highlights gaps in understanding the mechanisms linking cutaneous viral infections to neurologic disease. We explore the principal mechanisms linking viral skin infections to central and peripheral nervous system damage, including direct neuroinvasion, immune-mediated injury, and vascular or endothelial dysfunction. Particular attention is given to herpesviruses, retroviruses, enteroviruses, and respiratory viruses, which have been associated with conditions such as dementia, multiple sclerosis, myelopathies, Guillain-Barré syndrome, and the post-acute neurologic sequelae of COVID-19. Furthermore, we discuss the role of neuroinflammation in viral-associated neurodegeneration and highlight emerging evidence supporting the recombinant zoster vaccine (Shingrix) as a potential modulator of neuroinflammatory processes and a protective factor against dementia. Conclusions: Cutaneous viral infections extend beyond local skin pathology, contributing to a broad spectrum of neurologic complications through intertwined infectious and inflammatory mechanisms. A clearer understanding of how peripheral viral activity shapes central nervous system vulnerability remains a major unmet need. A multidisciplinary approach integrating dermatologic and neurologic perspectives is essential for early recognition and prevention. While observational studies suggest that zoster vaccination may reduce viral reactivation and modulate neuroinflammatory pathways, definitive evidence of neuroprotection is still lacking. Future studies should clarify causal relationships, test mechanistic hypotheses regarding skin-brain immune crosstalk, and explore vaccine-mediated neuroprotection as a novel therapeutic strategy.
2025-10-28 | The Yin and Yang of Antibodies in Viral Infectious Diseases.
Antibodies are a cornerstone of the adaptive immune response, serving as key defenders against viral infections; however, they can also act as a double-edged sword, contributing to immune-mediated pathologies. This review advances a "Yin-Yang" framework to integrate the dual activities of antibodies. The protective 'Yin' functions are driven by high-affinity antibodies generated through processes like somatic hypermutation and class-switch recombination. These antibodies execute viral neutralization, activate the complement system, and engage Fc receptors (FcRs) to drive antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. These mechanisms form the immunological basis of effective vaccines, which aim to elicit durable and functionally specialized antibody isotypes like IgG and mucosal IgA. Conversely, the pathogenic 'Yang' of the response can be detrimental. This includes antibody-dependent enhancement (ADE) of infection, notably observed with flaviviruses, and the development of autoimmunity through mechanisms like molecular mimicry and bystander activation, which can lead to conditions such as multiple sclerosis and Guillain-Barré Syndrome. The balance between protection and pathology is tipped by a confluence of factors. These include viral evasion strategies like antigenic mutation and glycan shielding, as well as host-based determinants such as genetic polymorphisms in FcRs, immune history, and the gut microbiome. Understanding these molecular determinants informs the rational design of next-generation interventions. Promising strategies, such as Fc-region glyco-engineering and the design of tolerogenic vaccines, aim to selectively promote protective functions while minimizing pathological risks, offering a clear path forward in combating viral threats.
2025-10-18 | A systematic review of CRISPR applications in demyelinating peripheral nervous system disorders.
This review evaluates CRISPR-based strategies for myelin regeneration in peripheral demyelinating disorders, with a focus on Guillain - Barré syndrome (GBS) and Charcot - Marie - Tooth disease type 1A (CMT1A). It aims to identify current therapeutic approaches, delivery systems, and gaps in the literature. A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2010 onward, following PRISMA guidelines. Study quality was assessed using OHAT and SYRCLE tools, and 14 articles met the inclusion criteria. In GBS, CRISPR interventions primarily targeted antiviral immune regulation (AXL, IFI6, IFNL2), inhibition of viral entry mechanisms (Integrin αvβ5, SPCS1), and Schwann cell repair. In CMT1A, therapeutic approaches focused on correcting PMP22 overexpression. Lentiviral transduction was the most frequently used delivery method, with no major adverse effects reported. However, most studies were in vitro, and only two were in vivo, highlighting the need for further validation in animal models. CRISPR technology shows considerable potential for addressing peripheral nerve demyelination through precise genetic modifications that may enhance Schwann cell function and support myelin repair. Nevertheless, the field remains at an early discovery stage, with no near-term clinical applicability demonstrated.
small molecules
2026-07-31 | Pyruvate Kinase M2 Upregulation Is Associated With Guillain-Barré Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model.
This study aimed to investigate the potential involvement of pyruvate kinase M2 (PKM2) in the pathogenesis of Guillain-Barré syndrome (GBS). Mendelian randomization (MR) analysis was used to evaluate the causal association between PKM2 expression and GBS susceptibility, with mediation analysis performed to explore immune cell-mediated pathways. The association between PKM2 methylation and GBS risk was further examined using GoDMC mQTL data and GRT-qPCRWAS Data Hub profiling. To validate these findings experimentally, an experimental autoimmune neuritis (EAN) mouse model was established in male C57BL/6 mice (6-8 weeks) by immunization with P0180-199 peptide, with tissues collected at disease initiation (Day 8) and peak stage (Day 16). PKM2 expression dynamics, Th17/Treg (regulatory T cells) balance, and histopathological changes were assessed using, Western blot, immunohistochemistry, immunofluorescence, flow cytometry, and H&E/Luxol fast blue (LFB) staining. MR analysis revealed that elevated PKM2 expression in the tibial nerve was significantly associated with an increased risk of GBS (OR: 1.75-6.14, p < 0.05). In the EAN model, PKM2 expression in the sciatic nerve exhibited a time-dependent increase (p < 0.01), primarily localized to inflammatory infiltrates. Mechanistic studies demonstrated that PKM2 upregulation in CD4+ T cells was associated with promoted Th17 differentiation, as evidenced by the upregulation of IL-17a and RORγt (p < 0.05), concomitant with a reduction in Treg cells (p < 0.01). To further elucidate the upstream epigenetic regulation, the association between PKM2 methylation and GBS risk was investigated using GoDMC mQTL data. Among the four selected methylation sites, two-sample MR analyses indicated that cg24327132 were positively associated with GBS risk (p < 0.05). Furthermore, analysis of the GWAS Data Hub revealed that cg24327132 appeared to be preferentially hypomethylated in adaptive immune cells including regulatory T cells, CD4+ T cells, and B cells (Beta ≈ 0-0.05), visually distinct from innate immune populations (Beta ≈ 0.10-0.20), suggesting that perturbation of this hypomethylated state may dysregulate PKM2 expression and contribute to GBS susceptibility. PKM2 upregulation is associated with GBS risk and immune dysfunction. PKM2 methylation may represent a key regulatory mechanism underlying this association. PKM2 may represent a mechanism target warranting further therapeutic investigation.
2026-06-25 | Pediatric GBS-myelitis overlap syndrome: Severe phenotype, treatment response, and neurological outcomes.
To characterize the clinical features, treatment responses, and outcomes of pediatric patients with Guillain-Barré syndrome (GBS) and concurrent myelitis. Clinical and auxiliary data from 22 pediatric patients (5 from local hospital and 17 by reviewing the previous literatures) with GBS and myelitis were analyzed. Parameters included demographics, neuroimaging, cerebrospinal fluid (CSF) findings, immunotherapy regimens, and outcomes stratified by the Hughes Functional Grading Scale. In this pediatric cohort (median age: 11.0 years; male-to-female ratio ≈1:1), GBS with concurrent myelitis manifested with flaccid paralysis in 95.5% of cases, including quadriplegia (59.1%), accompanied by diminished deep tendon reflexes (90.9%). Sensory disturbances were documented in 77.3% of patients, while autonomic dysfunction featured urinary impairment (68.2%) and respiratory failure requiring ventilation (52.6%). Neurodiagnostic findings universally demonstrated long-segment spinal cord lesions (>5 vertebral segments) on MRI and albuminocytological dissociation in CSF analysis. First-line immunotherapy comprised intravenous immunoglobulin (IVIG) and corticosteroids. Severity stratification identified a severe group (Hughes Grade ≥ 3; n = 13) characterized by: tetraplegia (92.3%), respiratory failure (69.2%), extensive spinal cord edema (84.6%), prolonged hospitalization (median: 6.0 weeks), higher residual sequelae (69.2%). The majority of patients in this group (92.3%) necessitated combination therapy with IVIG and corticosteroids. Pediatric GBS with myelitis frequently presents with severe neurological involvement. Although combination immunotherapy demonstrates efficacy, the severe subgroup shows significant residual morbidity. Early aggressive intervention is warranted to mitigate long-term disability.
2026-06-17 | [Guillain-Barré syndrome following allogeneic hematopoietic stem cell transplantation in a pediatric patient: a case report and literature review].
A 10-year-old girl diagnosed with hyper-IgE syndrome for more than six years developed dizziness and symmetrical progressive limb weakness one week prior to hospital admission, occurring 4 months after allogeneic hematopoietic stem cell transplantation. On post-transplant day 121, dizziness and progressive, symmetric limb weakness appeared. Cerebrospinal fluid analysis revealed albuminocytologic dissociation. Electromyography confirmed multiple peripheral nerve lesions, consistent with the diagnosis of Guillain-Barré syndrome. Intravenous immunoglobulin therapy showed limited efficacy, whereas corticosteroid therapy produced significant clinical improvement. Neurological symptoms fully resolved after treatment; however, severe chronic graft-versus-host disease occurred subsequently. Based on this case, related literature was reviewed and summarized to provide references for early diagnosis, mechanistic investigation, and treatment options.
2026-04-06 | Qualitative evaluation of pharmacological strategy for connective tissue diseases with Guillain-Barré syndrome: a systematic review.
To systematically evaluate the pharmacological management of Guillain-Barré syndrome occurring in the context of connective tissue diseases (CTD-GBS) and to investigate the relative efficacy of different treatment regimens on neurological outcomes. Case reports and series regarding CTD-GBS were systematically retrieved from PubMed, Embase, and Web of Science databases. A Generalized Linear Mixed Model (GLMM) was utilized to assess independent associations between treatment regimens and neurological improvement, adjusting for key covariates including mechanical ventilation (as a baseline severity marker) and the year of publication. A total of 105 CTD-GBS patients were identified, with systemic lupus erythematosus (SLE) being the most prevalent subtype (n=73). Multivariable GLMM analysis suggested that, compared to intravenous immunoglobulin (IVIG) monotherapy, intensive combination regimens specifically glucocorticoids combined immunosuppressants (GC + IS) demonstrated a potential association with higher odds of clinical improvement (adjusted Odds Ratio [aOR] = 30.90; 95% CI: 6.58-145.00; p < 0.001). Mechanical ventilation was identified as an independent negative predictor of recovery (aOR = 0.43; p = 0.037), while the year of publication did not significantly influence outcomes (p = 0.344). Descriptive analysis within the SLE-GBS subgroup corroborated these trends, with the GC + IS regimen achieving a clinical improvement rate of 88.9%. Preliminary evidence suggests that intensive immunosuppressive combination therapy, notably GC + IS, may offer advantages over traditional IVIG monotherapy in improving short-term neurological outcomes for CTD-GBS patients. However, given the reliance on retrospective case-based evidence and the potential for confounding by indication, these findings should be interpreted as hypothesis-generating clinical clues rather than definitive guidelines. Future large-scale, prospective studies utilizing standardized functional assessment scales are urgently required to validate these preliminary observations.
2026-04-03 | Methylprednisolone as an adjunct to intravenous immunoglobulin in pediatric Guillain-Barré syndrome: a prospective comparative study.
Guillain–Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children. Intravenous immunoglobulin (IVIG) is considered the standard therapy; however, the potential benefit of adjunctive corticosteroids remains uncertain.This study aimed to explore whether the addition of short-course intravenous methylprednisolone to IVIG may accelerate recovery and alleviate neuropathic pain in pediatric patients with GBS. A prospective, comparative study was conducted at Al-Azhar University Hospitals, enrolling 28 pediatric patients with clinically and electrophysiologically confirmed GBS. Participants were randomized into two equal groups: Group A received IVIG alone (1 g/kg/day for two days), while Group B received IVIG combined with pulse-dose methylprednisolone (30 mg/kg/day for five days). Clinical outcomes including time to initial improvement, unaided ambulation, Hughes Disability Score, neuropathic pain, and adverse events were assessed over a six-month follow-up period. Baseline characteristics were comparable between groups. The combination therapy group demonstrated faster initial improvement (median 3 vs. 4.5 days), earlier independent ambulation (21 vs. 28 days), and modest improvement in Hughes score at three months (median 0 vs. 1, p = 0.016), though clinical significance is limited. Neuropathic pain resolved completely in the steroid group but persisted in 57.1% of the IVIG-only group (p = 0.002). By six months, nearly all patients achieved complete recovery. Adverse events in the combination group were limited to mild weight gain and increased appetite. Short-course methylprednisolone as an adjunct to IVIG may provide early benefits, particularly in pain resolution, without major safety concerns. These findings are preliminary and hypothesis-generating, requiring confirmation in larger multicenter trials. These findings highlight a feasible and safe strategy that could be particularly valuable in resource-limited healthcare settings, though confirmation in larger multicenter trials is warranted.
cell therapies
2026-07-31 | Case Report: Guillain-Barré syndrome mimicking acute brainstem stroke with severe autonomic dysfunction-complete recovery after early plasma exchange.
Acute onset of bilateral ptosis, bulbar palsy, and quadriparesis typically raises suspicion for brainstem infarction. However, when neuroimaging is unrevealing, immune-mediated neuropathies such as Guillain-Barré syndrome (GBS) should be considered. This case highlights the diagnostic challenge and therapeutic response in a seronegative, rapidly progressive GBS variant with severe autonomic involvement. We report a 57-year-old previously healthy man who presented with acute right-sided weakness and dysarthria, progressing over 36 hours to bilateral ptosis, complete ophthalmoplegia, dilated pupils, bulbar palsy, flaccid quadriparesis, urinary retention, and paralytic ileus. Initial brain MRI-DWI was negative. CSF showed no albuminocytologic dissociation. Anti-ganglioside antibodies and neuromuscular junction antibodies were negative. Electromyography revealed motor-predominant polyneuropathy with sympathetic skin response abnormalities. A diagnosis of atypical GBS with severe autonomic involvement was made. Plasma exchange was initiated at 40 hours after onset, followed by a second session on day 5. The patient improved dramatically, walked independently by day 8, was discharged on day 15, and achieved complete recovery at 1 month. This case demonstrates that GBS can present as an acute brainstem stroke mimic with severe ileus and urinary retention, even in the absence of CSF abnormalities or detectable autoantibodies. Early plasma exchange may result in complete neurological recovery. Therefore, clinicians should maintain a high clinical suspicion for immune-mediated neuropathies in patients presenting with rapidly progressive stroke mimics accompanied by autonomic dysfunction.
2026-07-30 | Robot-assisted gait training using a robotic exoskeleton during inpatient rehabilitation in acute Guillain-Barré Syndrome.
A woman in her early 60s with acute Guillain-Barré syndrome (GBS) developed rapidly progressive tetraparesis and respiratory failure requiring non-invasive ventilation. Following intravenous immunoglobulin and medical stabilisation, she entered inpatient rehabilitation with severe weakness, poor truncal control and inability to ambulate. Despite intensive conventional therapy, early gait training was limited. Exoskeleton-based robot-assisted gait training (RAGT) using the Hybrid Assistive Limb (HAL; Cyberdyne Inc, Tsukuba, Japan) was introduced during inpatient rehabilitation as an adjunct to standard therapy. The patient completed 10 HAL sessions over a 15-day period without adverse events. During this time, progressive improvements in ambulatory distance and functional independence were observed. By completion of HAL training, she was able to ambulate 50 m with a walking stick and minimal assistance. She subsequently continued conventional rehabilitation and achieved independent ambulation by discharge. This case suggests that HAL-based RAGT may be a feasible adjunct to inpatient rehabilitation in medically stable patients with acute GBS. The intervention was well tolerated in this patient. Further studies are required to establish patient-selection criteria, optimal timing and the effectiveness of exoskeleton-assisted gait training in GBS.
2026-07-11 | Impact of Gut Microbiota Dysbiosis in Treatment Outcomes of Guillain-Barré Syndrome.
The gut-microbiota plays a significant role in neuro-autoimmune diseases, like Guillain-Barré syndrome (GBS), a post-infectious disorder of the peripheral nervous system (PNS). By altering host immunity, gut dysbiosis may impact the standard therapeutic efficacy of intravenous immunoglobulin (IVIg) and plasma exchange (PE) and thereby, disease progression in GBS. In this study, we investigated the impact of gut-microbiota diversity on therapeutic outcomes of IVIg and PE in patients with GBS. We enrolled 60 patients with GBS categorized into three treatment groups: IVIg-treated, PE, and supportive-care along with 60 age-sex-matched healthy controls from Bangladesh. Fecal microbial DNA was extracted at different timepoints and sequenced. Clinical and sequenced data were analyzed using the Qiime2-Dada2 pipeline. Gut-microbial diversity significantly differed in patients with GBS before and after treatment (Shannon: p = 0.037; Evenness: p = 0.012), particularly in IVIg-treated patients, showing significant changes after 6-month treatment (Shannon: p = 0.034; Evenness: p = 0.011). Beta diversity indicated microbiota restoration in IVIg-treated patients toward a healthy state after treatment (p ≤ 0.001). Phylum Actinobacteriota (p = 0.026), genera Bifidobacterium (p = 0.006), and Enterococcus (p ≤ 0.0001) were relatively abundant in severe patients. Mechanically ventilated patients showed significant gut-microbial diversity (Unweighted-UniFrac; p ≤ 0.001). Biomarker analysis identified a higher abundance of Eubacterium, Bacteroides, Escherichia-Shigella, and Actinomyces in GBS patients. Our exploratory study indicates that gut microbiota dysbiosis is associated with GBS severity and IVIg-treatment outcomes. IVIg-treatment promoted partial restoration of microbial diversity, suggesting a potential immunomodulatory effect mediated through the microbiota. Further studies using meta-transcriptomics are warranted to define functional consequences of microbial shifts in treatment responses of GBS.
2026-06-22 | Exploring the Feasibility and Patient Acceptance of RAGT for Overground Ambulation in Adults With Guillain-Barré Syndrome: A Scoping Review.
To review the current literature on the feasibility as well as weaknesses and strengths of robot-assisted gait training (RAGT) in the rehabilitation of gait in adult patients with Guillain-Barré syndrome (GBS). This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Scoping Reviews guidelines. A systematic search between November 2024 and May 2025 of PubMed, Cochrane Library, Embase, Canadian Agency for Drugs and Technologies in Health (CADTH) Grey Matters, and citation mining was performed to evaluate for relevant studies. All studies involving the use of RAGT in adults (≥18y) diagnosed with acute inflammatory demyelinating polyneuropathy or GBS were included. Eligible study designs comprised case reports, case series, feasibility studies, and randomized controlled trials. The search yielded 11 potentially relevant articles. Study selection was conducted in 2 stages: title and abstract screening followed by full-text review. Discrepancies between the 2 independent reviewers were resolved through discussion until consensus was achieved. Four studies met the inclusion criteria, comprising 2 case reports, 1 mixed-methods feasibility study, and 1 cross-sectional study, with a total of 19 participants. Across studies, RAGT was generally reported to be feasible, well tolerated, and acceptable to patients, with no major safety concerns. Reported benefits included the ability to initiate overground ambulation, high-intensity repetitive gait practice, and reduced physical burden on therapists. Patient acceptance was supported by positive user experiences, adherence to training sessions, and completion of prescribed protocols, although outcome measures and reporting were inconsistent. The current evidence base for RAGT in adults with GBS is limited but suggests that it is a feasible and acceptable adjunct to conventional rehabilitation. Although functional improvements were reported, conclusions regarding effectiveness remain constrained by small sample sizes and study heterogeneity. Further prospective and methodologically robust studies are needed to better characterize feasibility, patient experience, and implementation considerations of RAGT in this population.
2026-05-11 | Microbiota and Guillain-Barré syndrome: role of microbial metabolites, biomarkers, and emerging therapeutic strategies.
Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy that follows infection and is characterized by immune-mediated demyelination or axonal injury of the peripheral nervous system. While established triggers such as Campylobacter jejuni are well recognized, increasing evidence implicates the gut microbiota as a key modulator of immune responses relevant to GBS pathogenesis. The intestinal microbiota produces a diverse array of bioactive metabolites, including short-chain fatty acids (SCFAs), tryptophan-derived indoles, and neurotransmitter-like molecules, which influence immune tolerance, gut barrier integrity, and neuroinflammatory signaling. SCFAs, particularly butyrate, exert anti-inflammatory effects and support epithelial and blood-nerve barrier function. Microbial tryptophan metabolites regulate astrocyte and microglial activity via aryl hydrocarbon receptor (AHR) signaling, thereby restraining central and peripheral neuroinflammation. In contrast, dysbiosis-associated metabolites such as lipopolysaccharide (LPS) may enhance systemic inflammation, disrupt immune tolerance, and promote autoantibody production through mechanisms including molecular mimicry. Studies suggest that specific microbial taxa and metabolite signatures may serve as diagnostic or prognostic biomarkers in GBS, offering insights into disease susceptibility and progression. Microbiota-targeted therapeutic strategies are emerging as promising adjuncts to immunotherapy. Probiotics and prebiotics may restore beneficial microbial communities and rebalance immunoregulatory metabolite production, while host-directed metabolic interventions such as creatine supplementation may further support mitochondrial function, immunometabolic homeostasis, and neuroprotection. Fecal microbiota transplantation (FMT), though still experimental in GBS, has shown benefit in related neuroinflammatory disorders by reestablishing eubiosis and dampening immune activation. Future studies integrating metagenomic, metabolomic, and immunologic profiling in well-characterized GBS cohorts are essential to validate these findings and advance personalized microbiota-based interventions.
antibodies
2026-08-03 | Corrigendum to "Elsberg Syndrome with Albuminocytologic Dissociation - A Guillain-Barré Syndrome Mimic or Guillain-Barré Syndrome Variant?".
[This corrects the article DOI: 10.1177/19418744241233621.].
2026-07-29 | Clinical spectrum and prognostic features of patients seropositive for anti-GD1a antibody.
Anti-GD1a antibodies are associated with a range of immune-mediated neuropathies, particularly acute motor axonal neuropathy (AMAN) and other Guillain-Barré syndrome (GBS) variants. However, their full clinical spectrum and prognostic significance remain unclear due to limited systematic studies. Here, we investigated the clinical phenotypes, serological profiles, cerebrospinal fluid (CSF) characteristic, and therapeutic outcomes associated with anti-GD1a antibodies. The clinical, paraclinical and therapeutic data were retrospectively collected and analyzed from 19 Chinese patients who tested positive for anti-GD1a antibodies. The mean age at onset in this cohort was 50.6 years. Among the 19 patients, 14 (74%) presented with acute syndromes. The remaining five patients (26%) exhibited features consistent with chronic neuropathies. Common manifestations included absent tendon reflexes (84%), limb weakness (84%), sensory impairment (58%), and cranial nerve involvement (53%). Isolated anti-GD1a antibody positivity was observed in only 5 patients, while others had co-existing antiganglioside antibodies, most commonly anti-GQ1b, and anti-GM1. Electrophysiological studies revealed axonal and demyelinating neuropathic patterns. Patients with cranial nerve involvement and albuminocytologic dissociation were associated with higher modified Erasmus GBS Outcome Score (mEGOS). Immunotherapy was effective in acute cases, with 57% achieving complete recovery at 6-month follow-up. Patients seropositive for anti-GD1a antibody exhibits significant clinical and electrophysiological heterogeneity and frequently coexists with other antiganglioside antibodies. Acute presentations generally respond well to immunotherapy, while chronic cases require individualized management.
2026-07-23 | Neurological Manifestations of Mycoplasma pneumoniae Infection in Hospitalized Adults During the 2023-2024 French Epidemic, Clinical Characterization and Comparative Outcomes: A Multicenter Study.
Mycoplasma pneumoniae (MP) primarily causes respiratory infections but can lead to neurological manifestations. This study aimed to characterize these manifestations in adults during an epidemic. The national MYCADO cohort included 1309 adults hospitalized with MP infection during the 2023-2024 French epidemic. An ancillary study identified and described MP-related central (CNS) and peripheral (PNS) nervous system manifestations. Data were retrospectively extracted from medical records, with clinical follow-up up to 3 months after discharge. Twenty-eight patients with neurological manifestations attributable to MP were identified (2.1% of the cohort). Of these, 19 affected the CNS, including encephalitis (n = 8), myelitis (n = 3), encephalo-myelitis (n = 2), isolated meningitis (n = 6), and cerebral vasculitis (n = 1). Nine involved the PNS: Guillain-Barré syndrome (n = 6), peripheral polyneuropathy (n = 2), and multifocal neuropathy (n = 1). The median age (interquartile range) was 35 years (29-49) years; 60.7% were men. Neurological symptoms appeared a median of 7 days after MP infection onset. Nearly half (46.4%, n = 13) required intensive care; neurological failure was the leading cause of intensive care unit transfer (12/13, 92.3%). Compared with MP patients without neurological manifestations, those with neurological involvement had longer hospital stays (13 vs 9 days; P < .001), more frequent invasive mechanical ventilation (35.7% vs 4.2%; P < .001), and more rehabilitation transfers (42.8% vs 4.3%; P < .001). At discharge, neurological sequelae were present in 47.3% of CNS patients and all Guillain-Barré syndrome (GBS) patients. At 3 months, sequelae persisted in 36.8% of CNS patients and all GBS patients. In adults, MP infection causes rare but diverse and frequently severe neurological manifestations that worsen clinical course and result in long-term disability.
2026-07-17 | Clinical outcomes and safety of efgartigimod in Guillain-Barré syndrome: a retrospective observation study.
Guillain-Barré syndrome (GBS) is a severe acute autoimmune neuropathy with limited established therapeutic options. Efgartigimod, a human IgG antibody Fc fragment, can increase IgG degradation, which thus may be a promising therapeutic medicine for GBS. The aims of this study were to evaluate the clinical effectiveness and safety of efgartigimod in GBS patients. A retrospective study was conducted on GBS patients at the first affiliated hospital of Zhengzhou university and Nanyang central hospital from February 2024 to June 2025. The medical records of patients received IVIg, efgartigimod, or IVIg sequential efgartigimod (ISE) were reviewed. Disease severity was evaluated using GBS disability score (GBS-DS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score at baseline, week1, week2, week3, week4, and the final follow-up. The primary outcome was the proportion of good improvement, defined as a reduction of at least 2 points in the GBS-DS score compared to the baseline. All adverse events occurred during the treatment period were documented. 52 patients were enrolled and received IVIg (n=20), efgartigimod (n=16), or ISE (n=16). Good improvement was higher in the efgartigimod group than IVIg group both at week 2 (37.5% vs. 0%, p<0.01) and the final visit (81.3% vs. 40.0%, p=0.02). Throughout follow-up, the proportion with GBS-DS ≤1 in the efgartigimod group was consistently higher compared to the other two groups. Although not statistically significant, the mean time to reach GBS-DS ≤1 was shorter in the efgartigimod group (2.6± 1.2 weeks) compared to the IVIg (3.1 ± 1.1 weeks), In the ISE group, the average time to achieve GBS-DS ≤ 1 was 2.8 ± 1.2 weeks. Regarding safety, the incidence of treatment-related adverse events (TEAEs) was lower in the efgartigimod group18.8% (3/16) than in the IVIg50.0% (10/20) and ISE 43.8% (7/16) groups. Based on the preliminary finding, the retrospective real-world data suggesting a potential signal of benefit for efgartigimod in GBS, with no new safety concerns identified. However, this study cannot establish comparative efficacy given the methodological limitations, and large-scale well-controlled head-to-head trials remain imperative.
2026-07-15 | A Large Community Outbreak of Guillain-Barré Syndrome in Pune City, India, 2025.
Guillain-Barré syndrome (GBS) is a rare and potentially fatal immune-mediated disorder. During a large community outbreak in Pune City, India, investigations of GBS cases were conducted to identify the causes of antecedent or concurrent infections using serological and molecular methods. Water and poultry samples were also tested to determine the source of infection. From January to March 2025, 230 GBS cases, including 12 deaths (case fatality ratio 5.2%), were investigated. The cases were concentrated in Southwest Pune. All age groups were affected, with a male-to-female ratio of 2.2:1. Antecedent illness was reported in 147 (63.9%) cases, primarily diarrhea (37%). Among 193 cases, 108 (56%) were linked to infectious agents. Campylobacter jejuni (C. jejuni) infection was confirmed in 72 (48.7%) of 148 cases. Norovirus was confirmed in 40 (22.2%) of 180 cases, either as a coinfection (n = 19) or alone (n = 21). Water contamination was detected, with positive results for Campylobacter (n = 1/208) and norovirus (n = 8/208). Among 66 fecal samples from poultry, Campylobacter and norovirus were detected in 24 and five samples, respectively. No evidence of toxins was found in the nine water samples tested representatively. A significant GBS outbreak occurred in Pune City in early 2025, preceded by an acute diarrhea outbreak. A mixed etiology of the GBS outbreak was confirmed, with C. jejuni the leading cause in nearly half of the cases. Norovirus infection was also identified in more than one-fifth of the cases. Water contamination by both agents was detected, along with a possible link to poultry as a source of infection.
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2026-06-12 | A recombinant IgG1 Fc-domain protein ameliorates inflammatory demyelinating peripheral neuropathy.
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated inflammatory neuropathies characterized by T cell- and/or autoantibody-driven injury to peripheral nerves. Although intravenous immunoglobulin (IVIg) is effective in both conditions, its use is limited by high dosing requirements, supply constraints, and manufacturing complexity. NVG-2089 is a recombinant IgG1 Fc-domain protein engineered to selectively agonize type II Fc receptors, promoting anti-inflammatory signaling through expansion of regulatory T cells (Tregs) and upregulation of the inhibitory Fcγ receptor FcγRIIB. Its efficacy in immune complex-mediated disease and T cell-driven neuroinflammation prompted evaluation of its therapeutic potential in an animal model of inflammatory demyelinating neuropathy. We conducted a randomized, blinded preclinical study in the spontaneous autoimmune peripheral polyneuropathy model, a well-established murine model of inflammatory demyelinating neuropathy. Animals were treated with NVG-2089, high-dose IVIg, or vehicle. Outcomes included behavioral performance, nerve electrophysiology, peripheral nerve morphometrics, immunohistochemistry, and flow cytometric immunophenotyping. Both NVG-2089 and IVIg stabilized motor and sensory performance, preserved compound muscle action potential (CMAP) amplitudes, and attenuated demyelination-associated prolongation of distal latency and CMAP duration. Morphometric analyses demonstrated preservation of myelinated fiber density and normalization of g-ratio distributions in both treatment groups. Immunophenotyping indicated an expansion of functionally activated CD25+CD39+ Tregs in the spleen, along with increased FcγRIIB expression on B cells, monocytes, and dendritic cells across systemic and nerve-associated compartments, consistent with engagement of shared anti-inflammatory pathways. NVG-2089 demonstrated robust neuroprotective efficacy comparable to IVIg while requiring a substantially lower protein dose. These findings support NVG-2089 as a promising, dose-efficient alternative to IVIg for the treatment of inflammatory demyelinating neuropathies, including GBS and CIDP.
2026-05-08 | Varicella-zoster virus infection triggering GD3 antibody-positive variant Guillain-Barré syndrome: a case report and literature review.
Bilateral facial palsy variant Guillain-Barré syndrome (GBS) is a distinct clinical subtype. As an acute immune-mediated polyradiculoneuropathy often triggered by infections, varicella-zoster virus (VZV) is a rare yet significant precipitating factor for this variant. Anti-ganglioside antibodies, particularly anti-GD3, are involved in the pathogenesis of GBS, but their significance in VZV-associated bilateral facial palsy subtype remains incompletely elucidated. We report a 46-year-old female who developed acute bilateral facial palsy and limb sensory deficits following VZV infection. Serum anti-ganglioside testing confirmed GD3 IgG positivity, and cerebrospinal fluid analysis revealed albuminocytological dissociation. Nerve conduction studies supported a demyelinating polyneuropathy, and the patient showed significant improvement after intravenous immunoglobulin therapy. This case suggests that VZV may act as a potential trigger for GD3 antibody-positive variant GBS. Early immunotherapy may improve outcomes, emphasizing the need for systematic antibody testing in atypical presentations of this variant GBS. Further studies are required to clarify the pathophysiological role of GD3 antibodies in VZV-associated variant GBS.
2025-11-05 | Diagnostic and therapeutic potential of resolvin D1 in Guillain-Barré syndrome.
Most neuroimmune diseases are incurable and require lifelong immunotherapy, whereas Guillain-Barré syndrome (GBS), a peripheral nervous system autoimmune disorder, has a relatively favorable prognosis. Investigating the molecular disparities underlying recovery between GBS and other neuroimmune diseases may facilitate the development of innovative therapeutic strategies. This study explored the diagnostic and therapeutic potential of resolvin D1 (RvD1), a specialized pro-resolving mediator that promotes inflammation resolution and tissue regeneration, in GBS and its animal model experimental autoimmune neuritis (EAN). Serum RvD1 levels were measured in 218 participants from two cohorts, including healthy controls (HCs), GBS patients, and those with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or stroke. The diagnostic accuracy was evaluated via the area under the receiver operating characteristic (ROC) curve (AUC). RvD1 was administered to EAN and experimental autoimmune encephalomyelitis (EAE, an MS animal model) to assess its therapeutic efficacy. Serum RvD1 was elevated in GBS patients, demonstrating high diagnostic accuracy in differentiating GBS patients from HCs (cohort 1: AUC 0.72; cohort 2: AUC 0.93), MS/NMOSD patients (cohort 1: AUC 0.83), and stroke patients (cohort 1: AUC 0.68). The RvD1 level continued to increase as GBS progressed and was positively correlated with disease severity, ventilator dependence, and axonal neuropathy. In EAN, RvD1 and its synthetase/receptor were upregulated in serum, spleen, and sciatic nerve, exhibiting tissue-specific inflammation resolution patterns across disease phases. RvD1 treatment promoted inflammation resolution in EAN, as evidenced by attenuated disease severity and autoimmune responses, with its therapeutic effect was translatable to EAE. RvD1 may serve as a biomarker for both diagnosing GBS and monitoring disease severity. It represents a potential immunotherapeutic agent for GBS and other neuroimmune disorders. Elucidating the molecules associated with recovery in patients with GBS may facilitate the discovery of novel therapeutic strategies for neuroimmune disorders.
2025-10-14 | Exacerbation of demyelinating polyneuropathy after adoptive cell therapy with tumour-infiltrating lymphocytes by metastatic melanoma.
Adoptive cell therapy (ACT) with tumour-infiltrating lymphocytes (TIL) is an effective personalised immunotherapy for patients with advanced pretreated melanoma. For TIL-ACT, tumour-specific T cells are expanded from excised tumour samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous tumour-infiltrating lymphocytes are reinfused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Thereafter, activation of tumour-infiltrating lymphocytes in the patient is supported by the administration of high-dose IL-2. Although effective, there is a need for enhancement of TIL-ACT in terms of effectiveness and toxicity. Most of the toxicity in this multistep, complex treatment regimen is due to the preparative chemotherapy and high-dose IL-2 treatment. At University Hospital Basel, we are currently evaluating an experimental approach of TIL-ACT in which we replace high-dose IL-2 by in vivo tumour-infiltrating lymphocyte activation with ANV419, a novel antibody-cytokine fusion protein consisting of IL-2 fused to an anti-IL-2 monoclonal antibody, in an ongoing phase I trial (BaseTIL-03M). The primary endpoint of the study is safety. We herein describe the case of a patient included in the BaseTIL-03M trial with chronic inflammatory demyelinating polyneuropathy who received TIL-ACT with ANV419 and developed an acute polyneuropathy of Guillain-Barré syndrome.
2025-08-24 | Design of Hyperglycosylated Zika Virus E Proteins that Focus Antibody Recognition on the Complex E Dimer Epitope.
Zika virus (ZIKV) and dengue virus serotypes 1-4 (DENV1-4) are flaviviruses spread by Aedes mosquitoes. ZIKV infection can cause Guillain-Barré syndrome and microcephaly, while severe dengue can lead to hemorrhagic fever and death. DENV infection of ZIKV-immune individuals is linked to severe clinical outcomes due to antibody-dependent enhancement (ADE) of infection. Thus, the development of broadly protective vaccines is an important objective. We focus on the E dimer epitope (EDE) of ZIKV, which is targeted by broadly neutralizing antibodies that protect against ZIKV and DENV1-4. We engineered ZIKV E dimer variants containing non-native asparagine-linked glycosylation sites to block antibody responses to regions outside the EDE using a structure-based iterative design approach. One candidate, SC30m53, bound EDE mAbs but not other mAbs and induced a potently neutralizing response against ZIKV and moderately cross-neutralizing responses against DENV1-3 in mice. These findings suggest that hyperglycosylation provides a promising approach to focusing the immune response on key epitopes.
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2026-07-17 | COVID-19 mRNA Vaccination Reduces Guillain-Barré Syndrome Risk: Evidence from a Large Longitudinal Cohort Study.
The association between COVID-19 vaccination and Guillain-Barré syndrome (GBS) has been previously investigated with inconsistent results, largely due to limited data and lack of concurrent controls. To address this problem, a large longitudinal cohort study was conducted using National COVID Cohort Collaborative (N3C) data. While COVID-19 infection was associated with increased GBS occurrence, COVID-19 vaccination was associated with significantly reduced GBS risk relative to unexposed (unvaccinated and uninfected) control, corresponding to a 61% lower 30-day risk (incidence risk ratio: IRR = 0.39, P < 0.01), consistent with multivariable Cox regression showing a similar reduction (adjusted hazard ratio: aHR = 0.41, P < 0.01). This protective association was observed only among recipients of mRNA vaccines (BNT162b2: IRR = 0.38, P < 0.01; mRNA-1273: IRR = 0.24, P < 0.01), but not among recipients of adenoviral-vector vaccines (IRR = 1.38, P > 0.05). Prior COVID-19 vaccination also reduced infection-associated GBS risk. Additional factors associated with GBS risk included sex, vaccine dose, and pre-existing comorbidities such as stroke, neurological disorders, and autoimmune diseases. Overall, our N3C large-scale study provides evidence that COVID-19 mRNA vaccination reduces GBS risk, supporting the safety profile of mRNA vaccines and warranting further mechanistic investigation.
2026-04-01 | The EGR1/ZFP36 axis governs glycosphingolipid metabolic reprogramming in monocyte-derived macrophages in guillain-barré syndrome.
Guillain-Barré syndrome (GBS) is an immune-mediated demyelinating disorder of peripheral nerves with an unclear pathogenesis. This study integrated GBS clinical single-cell data with EAN model transcriptome data, establishing in vivo and in vitro experimental systems to reveal, for the first time, a novel mechanism involving EGR1-ZFP36 and its mediated metabolic reprogramming in GBS pathogenesis. Findings indicated that the transcription factor EGR1 and its predicted target gene ZFP36 were downregulated in both GBS patients and EAN rats. Molecular interaction validation confirmed that EGR1 directly bound to and activated the transcription of ZFP36. Transcriptomic and metabolomic analyses revealed that the EGR1/ZFP36 axis specifically drove macrophage reprogramming toward a glycosphingolipid metabolism-active state. Functionally, EGR1 overexpression promoted the expression of key glycosphingolipid metabolism genes (HEXA, HEXB) by upregulating ZFP36, thereby facilitating polarization toward the anti-inflammatory M2 phenotype. Animal experiments further demonstrated that EGR1 overexpression improved motor function and ameliorated myelin damage in the EAN model, with this protective effect being mediated by ZFP36. Collectively, this study reveals that EGR1 drives glycosphingolipid metabolic reprogramming in monocyte-derived macrophages by transcriptionally activating ZFP36, thereby regulating cellular polarization and participating in the demyelination process of GBS. This discovery not only provides a novel perspective on understanding the immunometabolic mechanisms of GBS but also lays a theoretical foundation for potential therapeutic strategies targeting the EGR1-ZFP36-glycosphingolipid metabolism axis.
2025-12-30 | A Review of Cutaneous Viral Infections and Their Potential Role in Neurologic Diseases.
Background: Cutaneous viral infections, defined as viral pathogens that either primarily affect the skin (e.g., herpesviruses, enteroviruses) or frequently produce dermatologic manifestations despite systemic tropism (e.g., HIV, SARS-CoV-2), can trigger systemic inflammatory and neurotropic responses that extend their impact to the nervous system. A growing body of evidence suggests that viruses with dermatologic manifestations may play a significant role in the pathogenesis of neurologic disorders. Summary: Although individual viruses have been studied in isolation, the skin-brain axis in viral infections remains incompletely characterized. This review synthesizes existing knowledge and highlights gaps in understanding the mechanisms linking cutaneous viral infections to neurologic disease. We explore the principal mechanisms linking viral skin infections to central and peripheral nervous system damage, including direct neuroinvasion, immune-mediated injury, and vascular or endothelial dysfunction. Particular attention is given to herpesviruses, retroviruses, enteroviruses, and respiratory viruses, which have been associated with conditions such as dementia, multiple sclerosis, myelopathies, Guillain-Barré syndrome, and the post-acute neurologic sequelae of COVID-19. Furthermore, we discuss the role of neuroinflammation in viral-associated neurodegeneration and highlight emerging evidence supporting the recombinant zoster vaccine (Shingrix) as a potential modulator of neuroinflammatory processes and a protective factor against dementia. Conclusions: Cutaneous viral infections extend beyond local skin pathology, contributing to a broad spectrum of neurologic complications through intertwined infectious and inflammatory mechanisms. A clearer understanding of how peripheral viral activity shapes central nervous system vulnerability remains a major unmet need. A multidisciplinary approach integrating dermatologic and neurologic perspectives is essential for early recognition and prevention. While observational studies suggest that zoster vaccination may reduce viral reactivation and modulate neuroinflammatory pathways, definitive evidence of neuroprotection is still lacking. Future studies should clarify causal relationships, test mechanistic hypotheses regarding skin-brain immune crosstalk, and explore vaccine-mediated neuroprotection as a novel therapeutic strategy.
2025-10-28 | The Yin and Yang of Antibodies in Viral Infectious Diseases.
Antibodies are a cornerstone of the adaptive immune response, serving as key defenders against viral infections; however, they can also act as a double-edged sword, contributing to immune-mediated pathologies. This review advances a "Yin-Yang" framework to integrate the dual activities of antibodies. The protective 'Yin' functions are driven by high-affinity antibodies generated through processes like somatic hypermutation and class-switch recombination. These antibodies execute viral neutralization, activate the complement system, and engage Fc receptors (FcRs) to drive antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. These mechanisms form the immunological basis of effective vaccines, which aim to elicit durable and functionally specialized antibody isotypes like IgG and mucosal IgA. Conversely, the pathogenic 'Yang' of the response can be detrimental. This includes antibody-dependent enhancement (ADE) of infection, notably observed with flaviviruses, and the development of autoimmunity through mechanisms like molecular mimicry and bystander activation, which can lead to conditions such as multiple sclerosis and Guillain-Barré Syndrome. The balance between protection and pathology is tipped by a confluence of factors. These include viral evasion strategies like antigenic mutation and glycan shielding, as well as host-based determinants such as genetic polymorphisms in FcRs, immune history, and the gut microbiome. Understanding these molecular determinants informs the rational design of next-generation interventions. Promising strategies, such as Fc-region glyco-engineering and the design of tolerogenic vaccines, aim to selectively promote protective functions while minimizing pathological risks, offering a clear path forward in combating viral threats.
2025-10-18 | A systematic review of CRISPR applications in demyelinating peripheral nervous system disorders.
This review evaluates CRISPR-based strategies for myelin regeneration in peripheral demyelinating disorders, with a focus on Guillain - Barré syndrome (GBS) and Charcot - Marie - Tooth disease type 1A (CMT1A). It aims to identify current therapeutic approaches, delivery systems, and gaps in the literature. A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2010 onward, following PRISMA guidelines. Study quality was assessed using OHAT and SYRCLE tools, and 14 articles met the inclusion criteria. In GBS, CRISPR interventions primarily targeted antiviral immune regulation (AXL, IFI6, IFNL2), inhibition of viral entry mechanisms (Integrin αvβ5, SPCS1), and Schwann cell repair. In CMT1A, therapeutic approaches focused on correcting PMP22 overexpression. Lentiviral transduction was the most frequently used delivery method, with no major adverse effects reported. However, most studies were in vitro, and only two were in vivo, highlighting the need for further validation in animal models. CRISPR technology shows considerable potential for addressing peripheral nerve demyelination through precise genetic modifications that may enhance Schwann cell function and support myelin repair. Nevertheless, the field remains at an early discovery stage, with no near-term clinical applicability demonstrated.
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Drug Discovery Landscape
11 orphan drug designations for Guillain-Barré syndrome.
11 orphan drug designations for Guillain-Barré syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Humanised IgG4 monoclonal antibody against C1q | antibodies | EMA | 2023-10-13 | — | Sinclair Regulatory Consulting Europe Limited |
Eculizumab [Soliris] | antibodies | EMA | 2022-10-11 | — | Alexion Europe |
eculizumab | antibodies | FDA | 2022-09-28 | — | Alexion Pharmaceuticals, Inc. |
imlifidase | proteins | FDA | 2018-02-14 | — | Hansa Medical AB |
humanized IgG4 monoclonal antibody binding to human C1q | antibodies | FDA | 2017-01-19 | — | Annexon, Inc. |
Recombinant protein derived from the saliva of the Ornithodoros moubata tick | proteins | EMA | 2016-06-27 | — | Akari Malta Limited |
nomacopan | proteins | FDA | 2016-05-10 | — | Akari Therapeutics Plc |
immune globulin (human) | antibodies | FDA | 2010-03-02 | — | Octapharma USA, Inc. |
Fampridine | small molecules | EMA | 2007-07-10 | — | Ulrich Granzer |
4-Aminopyridine | small molecules | FDA | 2005-12-14 | — | Merz Pharmaceuticals LLC |
Immune Globulin Intravenous (human) | antibodies | FDA | 2004-05-04 | — | ZLB Bioplasma AG |
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