RARE DISEASE
Anti-glomerular basement membrane disease
Anti-glomerular basement membrane disease
Anti-glomerular basement membrane disease
Synonyms: Anti-GBM syndrome, Goodpasture syndrome
Synonyms: Anti-GBM syndrome, Goodpasture syndrome
Synonyms: Anti-GBM syndrome, Goodpasture syndrome
Drug discovery
3
drugs
With orphan designations
Overview
Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune small-vessel vasculitis characterized by pathogenic autoantibodies targeting the non-collagenous domain of the α3 chain of type IV collagen in glomerular and alveolar basement membranes. It typically presents as rapidly progressive glomerulonephritis (RPGN) with or without alveolar hemorrhage. Early diagnosis and aggressive treatment with plasmapheresis, immunosuppression, and corticosteroids are critical to prevent irreversible kidney damage or fatal pulmonary hemorrhage [1][2][12].
Population
Incidence: ~1–2 cases/million/year, with higher rates in European and Asian populations [2][6][11].
Bimodal age distribution: peaks in young adults (20s–30s, often male-predominant lung involvement) and older adults (60+, more renal-predominant) [2][5][12].
Genetic predisposition: Strong HLA-DRB1*1501/1502 association in Caucasians [6][12].
Burden
Mortality: Up to 50% if untreated; respiratory failure is the leading cause of early death [6][12].
Renal outcomes: ~40–60% progress to ESRD, particularly with oligoanuria or >50% glomerular crescents at diagnosis [1][2][8].
Economic impact: High costs from prolonged ICU stays, dialysis dependence, and transplantation [2][10][12].
Therapies
First-line: Plasmapheresis (daily for 2–3 weeks) combined with cyclophosphamide and high-dose corticosteroids to remove antibodies and suppress production [1][5][8].
Second-line: Rituximab for refractory cases or cyclophosphamide contraindications [3][6].
Supportive care: Dialysis for kidney failure, mechanical ventilation for severe alveolar hemorrhage [2][7][12].
Categories: rare circulatory system diseases, rare renal diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare transplant-related disorders
Research Papers
698 drug discovery papers about Anti-glomerular basement membrane disease, with 5 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
698 drug discovery papers about Anti-glomerular basement membrane disease, with 5 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2026-09-23 | Outcomes of intensive care patients with acute small-vessel vasculitis: a 23-year single-centre experience.
Patients with fulminant small-vessel vasculitis (SVV) may require intensive care unit (ICU) admission, where mortality is high. We describe outcomes and prognostic factors in ICU patients with ANCA-associated vasculitis (AAV) and anti-glomerular basement membrane (anti-GBM) disease over a 23-year period. Patients admitted with acute manifestations of new or flaring AAV or anti-GBM disease were identified from our hospital ICU database (1999-2022). Patients treated solely in high-dependency areas were excluded. Primary outcomes were mortality at 30 and 90 days and development of end-stage kidney disease (ESKD). A matched case-control analysis (1:4) adjusted for age, gender, APACHE II score and admission year was performed for a patient subgroup. 85 cases (82% AAV, 15% anti-GBM) were identified, 80% newly diagnosed. Median APACHE II score was 19. Ventilatory support and continuous venovenous haemodiafiltration were required in 92% and 66% of cases, respectively. 30-day and 90-day mortality rates were 15% and 26%, respectively. Among 90-day survivors, 17 (28%) developed new ESKD. Vasculitis treatments included cyclophosphamide (59%), rituximab (53% of AAV patients) and plasma exchange (71%). These treatments were associated with 90-day and long-term survival. Treatment for vasculitis post-2008 was associated with 90-day and long-term survival, which was not mirrored in ICU controls. This coincided with improvements to the vasculitis service and therapeutic strategies. This single-centre study reports ICU outcomes for patients with fulminant SVV over 23 years. 30 and 90-day ICU mortality were comparable with other reported values. Improvement in mortality was associated with changes in vasculitis treatment protocols.
2026-08-22 | Concurrent Anti-glomerular Basement Membrane (Anti-GBM) Disease and Immunoglobulin A Nephropathy (IgAN) Presenting With Severe Pulmonary-Renal Syndrome: A Case Report.
Anti-glomerular basement membrane (anti-GBM) disease is a rare, aggressive autoimmune condition that typically presents as rapidly progressive glomerulonephritis and can be complicated by pulmonary haemorrhage. The co-occurrence of anti-GBM disease and IgA nephropathy (IgAN) is extremely uncommon, though increasingly recognised as a distinct clinical and pathological entity. We describe a 51-year-old Sudanese man who presented with acute hypoxaemic respiratory failure, haemoptysis, severe anaemia, and acute kidney injury. Testing showed high levels of anti-GBM antibodies, with negative anti-neutrophil cytoplasmic antibodies. Chest imaging revealed diffuse alveolar haemorrhage. Renal biopsy demonstrated crescentic glomerulonephritis with linear IgG staining along the glomerular basement membrane, alongside mesangial deposits dominated by IgA, confirming the presence of both diseases. Treatment included plasma exchange, high-dose corticosteroids, cyclophosphamide, and bronchial artery embolisation, which led to significant respiratory improvement and stabilisation of kidney function. A review of published cases suggests that individuals with this overlap may experience better renal outcomes than those with anti-GBM disease alone, though serious pulmonary-renal symptoms can still occur. This case highlights the need for accurate clinicopathological assessment and prompt initiation of anti-GBM-specific treatment.
2026-06-02 | Role of therapeutic plasma exchange (TPE) in the management of anti-glomerular basement membrane (anti-GBM) disease: A case series from tertiary-care hospital in India
Abstract: INTRODUCTION: Anti-glomerular basement membrane (anti-GBM) disease is an uncommon, autoimmune disease in which IgG antibodies bind to intrinsic antigens distributed along the length of glomerular basement membrane. It is characterized by rapid and progressive loss of renal function. The rationale of management is to suppress renal inflammation and production of autoantibodies (with immunosuppression), as well as removal of circulating pathogenic autoantibodies (with therapeutic plasma exchange [TPE]). However, there is a paucity of data on the role of TPE in the management of anti-GBM cases worldwide. MATERIALS AND METHODS: Three consecutive anti-GBM patients were admitted with common complaints of high-grade fever, chills, hematuria, and low urine output. In view of decreased renal function and strong suspicion of anti-GBM disease, the treatment protocol was initiated in accordance with the international Kidney Disease Improving Global Outcomes guidelines. RESULTS: All three patients had crescentic glomerulonephritis (crescents in more >80% glomeruli) on renal biopsy. Management was initiated with TPE and immunosuppression (methylprednisolone) and cytotoxic drug (cyclophosphamide). TPE was done until the anti-GBM antibody titer dropped to <10. Case 1 underwent TPE daily (12 sessions), and case 2 and case 3 underwent 14 and 9 sessions, respectively, of TPE alternating with dialysis. Renal function improved in cases 1 and 2, and routine dialysis was discontinued. Case 3 showed improvement initially until TPE was done; however, the disease progressed to end-stage renal disease, and the patient remains dialysis dependent. None of the patients had adverse reactions during TPE. CONCLUSION: TPE is an effective and safe conjunct in the treatment of anti-GBM disease as shown by complete reversal in two cases and partial response in the third patient.
2026-05-01 | C41-07 A Rare Case of Diffuse Alveolar Hemorrhage From Dual Positive Goodpasture Syndrome
Abstract Diffuse Alveolar Hemorrhage (DAH) is a life-threatening pulmonary emergency with the most common cause being a small-vessel vasculitis, such as ANCA-associated vasculitis (AAV) or anti-GBM vasculitis (Goodpasture syndrome). Concurrent positivity for both AAV and anti-GBM antibodies is rare but often signifies a more severe presentation and greater therapeutic challenge. A 53-year-old gentleman with no significant past medical history or oxygen requirement at baseline presented to the ED with one day of acute massive hemoptysis, dyspnea, and hypoxic respiratory failure requiring oxygen supplementation. Physical exam was notable for diffuse crackles bilaterally. Recent history was significant for hospitalization a month ago for new onset hematuria and an AKI, as well as an episode of hemoptysis. Kidney biopsy done at that time showed crescentic glomerulonephritis with positive anti-GBM, and serum studies showed positive PR3 ANCA antibodies at high titers. The patient was managed with pulse dose steroids, plasma exchange (PLEX), and rituximab, but missed a dose of scheduled Rituximab outpatient. CT scan showed bilateral patchy infiltrates (Image 1), concerning for DAH. A bronchoscopy with bronchoalveolar lavage showed washings with progressive bloody appearance, consistent with DAH. With rheumatology on board, the patient was diagnosed with AAV and Goodpasture syndrome overlap and treated with 5 sessions of plasma exchange, pulse-dose glucocorticoids, and one dose of cyclophosphamide. After his first session of plasma exchange and initiation of steroids, the patient’s hypoxemia resolved. After a two-week stay, the patient was discharged on a prednisone taper with a plan to continue cyclophosphamide outpatient. This case highlights a rare but clinically significant etiology of DAH—dual positive Goodpasture syndrome. This diagnosis is not only rare, but also associated with high mortality. A potential pathophysiology is AAV-associated damage to the glomerular basement membrane, leading to uncovering “hidden antigens” from the membrane and inducing the formation of antibodies. Classic treatment for AAV is glucocorticoids with rituximab or cyclophosphamide, whereas for Goodpasture is PLEX and immunosuppressive therapy. Dual-positive disease lies on a continuum between AAV and Goodpasture syndrome but behaves distinctly, often presenting with recurrent or refractory manifestations. Unlike isolated AAV or Goodpasture disease, management requires combining therapeutic principles from both. For this patient with dual disease, the key to successful management involved both PLEX and steroid therapy. This case emphasizes the importance of initial high suspicion for DAH in patients with hemoptysis, respiratory failure, and history of vasculitis. Also, dual-positive anti-GBM vasculitis exists and demands a tailored, hybrid treatment approach. This abstract is funded by: None
2026-02-03 | Plasma Exchange for Anti-GBM Disease With Dialysis Dependency: A Case Series on Clinical Outcomes and Safety.
The efficacy of plasma exchange (PEx) in patients with anti-glomerular basement membrane antibody (anti-GBM Ab) disease requiring renal replacement therapy (RRT) at diagnosis remains unclear. This study aimed to investigate the outcomes and safety of patients with uremic anti-GBM Ab disease undergoing PEx. We retrospectively analyzed nine patients confirmed by renal biopsy who received PEx using fresh frozen plasma or 5% human albumin solution and underwent hemodialysis (HD) concomitantly with standard immunosuppressive therapy. The outcome was determined as dialysis dependency, and safety was evaluated for adverse events. Two patients (22.2%) achieved dialysis independence at 10 and 11 months. Both patients had relatively preserved normal glomeruli (15.8%-37.2%) and achieved early remission. Retroperitoneal hemorrhage and recalcitrant anti-GBM Ab were noteworthy in other cases. PEx can facilitate renal recovery in selected patients with anti-GBM disease requiring RRT. Pathological evaluation may be useful to determine the intensity and duration of treatment, including PEx.
small molecules
2026-09-04 | HIF-1α regulates ADAM9 expression in Th17 cells during autoimmune disease.
Hypoxia-inducible factor 1α (HIF-1α) promotes T helper 17 (Th17) differentiation, but whether it regulates ADAM9 expression in Th17 cells during autoimmune nephritis remains unclear. Hypoxia enhanced Th17 differentiation and increased ADAM9 expression in a HIF-1α-dependent manner. HIF-1α deficiency reduced ADAM9 expression and impaired Th17 differentiation in vitro. In anti-glomerular basement membrane nephritis and B6.lpr lupus-prone mice, T cell-specific HIF-1α deletion attenuated renal pathology and reduced kidney-infiltrating CD4+ and IL-17A-producing T cells. These findings identify ADAM9 as a HIF-1α-regulated target in Th17 cells that may contribute to autoimmune renal inflammation.
2026-06-08 | Concurrent anti-GBM disease and p-ANCA vasculitis presenting as pulmonary-renal syndrome in a patient with chronic kidney disease: a case report.
The coexistence of anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis represents a rare autoimmune overlap syndrome that poses significant diagnostic and therapeutic challenges. This dual-positive presentation is particularly uncommon in patients with pre-existing chronic kidney disease (CKD) and offers valuable insight into the complexities of disease overlap and management. We report a 48-year-old woman with known CKD who presented with acute pulmonary-renal syndrome manifesting as dyspnea, productive cough, oliguria, and altered sensorium. Laboratory evaluation revealed markedly elevated serum urea and creatinine, raised inflammatory markers, and dual serologic positivity for anti-GBM and perinuclear ANCA (p-ANCA) antibodies, confirming dual-positive vasculitis. Serologic testing was initiated due to persistent respiratory distress and worsening renal function despite appropriate hemodialysis and empiric antibiotic therapy, prompting evaluation for an underlying autoimmune etiology. Testing was performed within the first 48 h of admission after failure of initial supportive measures to produce clinical improvement. The patient received urgent hemodialysis, high-dose intravenous corticosteroids followed by oral taper, plasmapheresis, and cyclophosphamide. Her neurological and respiratory symptoms improved gradually; however, dialysis dependence persisted due to underlying renal damage. Dual-positive anti-GBM and ANCA-associated vasculitis represents an uncommon but clinically significant overlap syndrome. The coexistence of both antibodies complicates diagnosis and management, especially in patients with CKD, where baseline renal dysfunction may mask active disease. Early recognition through serologic testing and prompt initiation of combined immunosuppressive and plasmapheresis therapy are critical to preventing irreversible organ injury. This case reinforces the importance of multidisciplinary management and long-term follow-up to monitor disease activity and prevent relapse. This case highlights the need to consider dual-positive anti-GBM and ANCA-associated vasculitis in patients presenting with unexplained renal deterioration or pulmonary symptoms, even in the context of CKD. Timely diagnosis and individualized immunosuppressive therapy can improve outcomes and reduce irreversible organ damage in this rare overlap syndrome.
2026-06-03 | Anti-Glomerular Basement Membrane Disease Combined with IgA Nephropathy: A Case Report and Literature Review.
Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease characterized by injury to small blood vessels in the kidneys and/or lungs. IgA nephropathy is the most common primary glomerular disease diagnosed in China. However, the co-occurrence of anti-GBM illness and IgA nephropathy has been infrequently documented in the literature. At present, its mechanism is unknown, the treatment approach is unclear, and the prognosis remains poor. Herein, we report a case of anti-GBM disease complicated with IgA nephropathy, in which renal function returned to normal state following treatment with a combination of prednisone and cyclophosphamide. This case suggests that in patients with anti-GBM disease and IgA nephropathy, the combination of glucocorticoids and cyclophosphamide may serve as an optimum treatment choice.
2026-05-13 | A case report of concomitant anti-glomerular basement membrane disease, IgA nephropathy, and membranous nephropathy.
The coexistence of anti-glomerular basement membrane (anti-GBM) disease, IgA nephropathy (IgAN), and membranous nephropathy (MN) represents an exceptionally rare glomerular pathology triad, with only one previously documented case. This study explores the underlying mechanisms linking these distinct entities and reports a novel case associated with persistent elevation of serum amylase and lipase, thereby expanding the clinical spectrum of this complex disease combination. A 51-year-old woman presenting with recurrent macroscopic hematuria and rapidly progressive renal dysfunction was diagnosed with simultaneous triple glomerulopathy based on positive anti-GBM antibodies and renal biopsy findings. An integrated therapeutic regimen was administered, including high-dose methylprednisolone pulse therapy, cyclophosphamide, intensive plasma exchange (PE), and hemodialysis. Treatment led to undetectable anti-GBM antibody titers within two months, successful discontinuation of hemodialysis by the third month, and complete resolution of hematuria. By the ten-month follow-up, proteinuria and serum creatinine levels significantly decreased, renal function stabilized with normal urine output, and no significant adverse events were observed. This case demonstrates the pathological coexistence of triple glomerulopathy. Although clinical improvement was observed after a combined regimen of early PE and immunosuppression, causality cannot be inferred from a single case. These findings provide hypothesis-generating insights for the management of similar complex cases and highlight the need for further research.
2026-04-06 | De novo antiglomerular basement membrane Goodpasture syndrome in a liver transplant recipient: balancing autoimmunity, allograft protection, and infection risk.
Antiglomerular basement membrane (anti-GBM) disease causes rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage (DAH) through autoantibodies directed against the α3 chain of type IV collagen. Evidence guiding adaptation of standard induction therapy (plasmapheresis, high-dose glucocorticoids, cyclophosphamide) for nonrenal solid organ transplant recipients remains scarce. A 55-year-old man, 9 years post-deceased donor liver transplantation for nonalcoholic steatohepatitis and maintained on low-dose tacrolimus, presented with pulmonary renal syndrome, severe metabolic acidosis, and high-titer anti-GBM antibodies. High-resolution computed tomography demonstrated bilateral ground-glass opacities consistent with DAH. He was treated with plasma exchange (seven sessions) and high-dose corticosteroids. Tacrolimus was discontinued, and maintenance immunosuppression was transitioned to mycophenolate mofetil with low-dose prednisone. Pulmonary hemorrhage resolved and anti-GBM titers declined to near the assay threshold; however, kidney function did not recover, and he remained dependent on hemodialysis. Four months later, he died of multidrug-resistant Acinetobacter pneumonia complicated by septic shock. To our knowledge, this represents the first reported case of de novo anti-GBM disease following liver transplantation. De novo Goodpasture syndrome can occur despite chronic immunosuppression in liver transplant recipients. Prompt recognition, individualized immunomodulation, and meticulous infection risk management are critical to controlling autoimmunity while preserving liver allograft function.
antibodies
2026-09-09 | Efficacy and safety of eculizumab-combined therapy for patients with anti-GBM disease.
The study aimed to evaluate the efficacy and safety of eculizumab in addition to conventional therapy for anti-glomerular basement membrane (anti-GBM) disease presenting rapidly progressive glomerulonephritis (RPGN). 42 patients with anti-GBM disease presenting with RPGN were included in this multicenter retrospective cohort study. All patients received intensive immunosuppressive therapy including intravenous methylprednisolone pulses followed by maintenance prednisone, in combination with at least two of the following: intravenous cyclophosphamide, therapeutic plasma apheresis, rituximab, or eculizumab. The cohort was stratified into two groups: the eculizumab group (n = 13) which received eculizumab (900 mg once weekly for 1-5 doses) in combination with other therapies, and the control group (n = 29) which did not receive eculizumab. Kidney survival at 12 weeks and 24 weeks, and adverse events (infections, metabolic alterations, laboratory abnormalities), ascertained via clinical and laboratory data. At 12 weeks, the eculizumab group showed significantly higher kidney survival compared with the control group (69.2% vs. 31.0%, p = 0.021). At 24 weeks, kidney survival remained numerically higher in the eculizumab group (66.7% vs. 40.7%, p = 0.081). Kaplan-Meier curves for renal survival by the Gehan-Breslow-Wilcoxon test, which places greater emphasis on early events, revealed a statistically significant difference between the groups (χ² = 4.137; p = 0.042); however, the difference assessed by the log-rank test did not reach statistical significance (χ² = 3.491; p = 0.062). There were no significant differences in the overall incidence of infections or other adverse events. Combined therapy with eculizumab showed improved early kidney survival for anti-GBM nephritis at 12 weeks, and did not increase the risk of adverse events. Prospective, large-sample studies with long-term follow-up are needed to validate its efficacy and safety.
2026-08-19 | Anti-glomerular basement membrane disease: A contemporary case series from a large university hospital center.
Anti-glomerular basement membrane disease (anti-GBM) is a rare autoimmune disorder characterized by autoantibodies targeting antigens in the glomerular and alveolar basement membranes, often leading to rapidly progressive glomerulonephritis and pulmonary hemorrhage. Contemporary real-world data on clinical presentation and long-term renal outcomes remain scarce. This study aims to examine the clinical and pathological features, as well as renal survival and long-term outcomes, in patients with anti-GBM disease. Retrospective single-center case series. All patients diagnosed with anti-GBM disease at a major Portuguese university hospital between 2003 and 2023 were included. Anti-GBM disease was defined as a compatible clinical presentation plus positive anti-GBM antibodies in circulation and/or biopsy-proven anti-GBM disease. Demographic, clinical, laboratory and therapeutic data were reviewed. Twenty-seven patients were included (mean age 58.7±22.0 years; 59.3% female). Renal involvement was universal and severe (mean serum creatinine 11.95±10.18mg/dL), with 92.6% requiring renal replacement therapy (RRT) at presentation. Alveolar hemorrhage occurred in 33.3% patients. Anti-GBM antibodies were detected in 92.6%; 29.6% were also ANCA-positive. Kidney biopsy (n=15) showed crescentic glomerulonephritis in 80% with a mean crescent burden of 60.9% and a median of 0% normal glomeruli (IQR 0-1). Most patients (92%) received immunosuppressive therapy, and 68% were treated with the standard combination of corticosteroids, cyclophosphamide, and plasma exchange. Renal recovery was limited: only 5 patients (18.5%) who required RRT at presentation recovered renal function, and 66.7% progressed to end-stage kidney disease (ESKD). Higher baseline serum creatinine, a lower proportion of normal glomeruli, and crescentic involvement >40% were significantly associated with ESKD. One- and five-year patient survival were 85.2% and 74.1%, respectively. No relapses occurred. Anti-GBM disease in this Portuguese cohort presented predominantly with severe acute kidney injury requiring RRT and was associated with poor renal recovery despite guideline-directed therapy. Histologic preservation of normal glomeruli and baseline kidney function were strongly associated with renal outcomes. These findings underscore the need for earlier recognition and timely referral, as well as the development of more effective targeted therapies for this severe glomerular disease.
2026-08-19 | Anti-Glomerular Basement Membrane Antibody Disease Complicated by Complement-Mediated Thrombotic Microangiopathy: A Case Report.
Anti-glomerular basement membrane (GBM) antibody disease rarely causes thrombotic microangiopathy (TMA). We herein report the case of a 75-year-old Japanese woman who developed refractory TMA during treatment for anti-GBM antibody disease. Although secondary TMA was initially suspected, persistent hemolytic anemia and thrombocytopenia despite plasma exchange, glucocorticoids, and cyclophosphamide led us to suspect complement-mediated TMA. Eculizumab was initiated after genetic testing for complement regulatory factors was performed. The patient became transfusion-independent within one week, and genetic testing identified the c.293C＞T (p.Thr98Ile) variant in CD46. Complement-mediated TMA should thus be considered in refractory cases, and anti-C5 monoclonal antibodies may be an effective therapeutic option.
2026-08-01 | Age-Related Differences in Anti-GBM Disease: Distinct Biology or Distinct Timing of Presentation?
We read with great interest the multicenter European study by Suhlrie et al.1 comparing outcomes in pediatric and adult anti-glomerular basement membrane (anti-GBM) disease. The study provides valuable contemporary data in a rare disorder and highlights important age-related differences in presentation and outcomes.
2026-07-07 | Immunological overlap stratification in anti-GBM disease: prognostic differences and serological correlations—a single-center retrospective cohort study
Background Anti-glomerular basement membrane (anti-GBM) disease is not a distinct, isolated entity but rather a condition that frequently overlaps with other autoimmune serological profiles. Most notably, it can coexist with antineutrophil cytoplasmic antibodies (ANCA), alongside a diverse spectrum of additional autoantibodies. Despite the occurrence of such antibody overlap in a subset of patients, their specific clinical manifestations and prognostic implications remain poorly defined and largely elusive. Methods This study retrospectively enrolled patients diagnosed with anti-GBM disease at the First Affiliated Hospital with Nanjing Medical University between January 2017 and January 2024. Based on serological profiles, enrolled patients were stratified into three cohorts: the classic anti-GBM group (anti-GBM antibodies positive alone), the ANCA-anti-GBM double-positive group, and the anti-GBM-non-ANCA autoantibody overlap group. Clinical, pathological, treatment, and outcome characteristics were systematically compared across the three groups. Additionally, landmark analysis was conducted to assess prognostic discrepancies across distinct time intervals. Results A total of 67 patients with anti-GBM disease were enrolled in this study, with 30, 18, and 19 cases allocated to the classic anti-GBM group, ANCA-anti-GBM double-positive group, and anti-GBM-non-ANCA autoantibody overlap group, respectively. The ANCA-anti-GBM double-positive group presented with the highest mean age at onset among the three cohorts. A statistically significant difference was detected in baseline anti-GBM antibody titers across the groups (median: 141.20 vs. 104.25 vs. 181.70; interquartile range: 102.90–257.70 vs. 52.15–137.07 vs. 121.05–555.40; p = 0.044). By contrast, no significant differences were noted in terms of other clinical characteristics, renal pathological findings, and therapeutic regimens. Although the overall survival rates showed no statistical discrepancy among the three groups, distinct trends were observed in early survival outcomes: the ANCA-anti-GBM double-positive group had the poorest early survival, followed by the anti-GBM-non-ANCA autoantibody overlap group, while the classic anti-GBM group exhibited the most favorable early survival profile. Conclusion This study identifies the distinct phenotypic traits of anti-GBM disease with concurrent other autoimmune antibodies, underscoring that sole reliance on anti-GBM antibody titers is inappropriate for prognostic judgment and treatment decision-making. For patients with anti-GBM disease overlapping with non-ANCA autoantibodies, intensive treatment regimens may be justified to achieve more favorable clinical prognosis.
proteins
2026-06-12 | Butyric Acid-Modified m-P14 Peptide Ameliorates Anti-Glomerular Basement Membrane Disease.
The non-collagenous domain 1 of the α3 chain of type IV collagen (α3(IV)NC1) is the primary autoantigen in anti-glomerular basement membrane (anti-GBM) disease. We previously developed a modified antigen-specific peptide, m-P14, derived from the nephritogenic epitope α3127-148, which ameliorated experimental anti-GBM nephritis. However, its short half-life limits clinical translation. This study evaluated a butyrate-conjugated derivative (m-P14-BA) to improve pharmacokinetic properties while preserving therapeutic efficacy. M-P14-BA and m-P14 were administered to α3127-148 immunized Wistar Kyoto rats in early and late treatment settings. Renal injury parameters and intrarenal inflammation were assessed, and pharmacokinetic profiles were evaluated following intraperitoneal administration in beagle dogs. M-P14-BA reduced proteinuria, crescent formation, glomerular IgG deposition, complement activation, and inflammatory cell infiltration, with overall efficacy comparable to m-P14 in early treatment settings. In late treatment settings, m-P14-BA was associated with a significant improvement in blood urea nitrogen levels and modest reductions in proteinuria and histopathological injury. Butyrate conjugation markedly improved pharmacokinetics, prolonging plasma elimination half-life by approximately 2.8-fold and increasing systemic exposure nearly fourfold. These pharmacokinetic improvements were associated with maintained therapeutic efficacy at a reduced dose, with 10 mg/kg m-P14-BA achieving effects broadly similar to those observed with 30 mg/kg m-P14. In summary, butyrate conjugation improves the pharmacokinetic profile of an antigen-specific therapeutic peptide while preserving therapeutic activity, suggesting a potential strategy to enhance the translational feasibility of peptide-based immunotherapy in anti-GBM disease.
2026-04-20 | Antiglomerular Basement Membrane Antibody-Associated Rapidly Progressive Glomerulonephritis in a Patient With Chromosome 10p Deletion
Anti-glomerular basement membrane antibodies cause rapidly progressive glomerulonephritis that regularly results in anuric, end stage kidney disease. Disruption of collagen structure can precipitate its onset. We here report the case of a 22-year-old man with severe disability due to chromosome 10p12 deletion who presented with anuric renal failure. Renal histology yielded severe crescentic glomerulonephritis, anti-glomerular basement antibodies were positive. Therapy with plasmapheresis, steroid pulse therapy and six courses of cyclophosphamide was complicated by severe anemia and nausea with vomiting. After six months, despite severe CKD, dialysis free life and vivacity undiscernible from his pre-glomerulonephritis state was achieved. The case underlines the importance of individualized patient care. Immunologic relevance of the fibrosis-modifying negative TGF-beta modulator "BMP and Activin Membrane-Bound Inhibitor (BAMBI), localized on chromosome 10p12, may be of interest.
2026-01-12 | Complement activation in anti-glomerular basement membrane disease before and after treatment with imlifidase.
The involvement of the complement system in anti-glomerular basement membrane (GBM) disease is well known but incompletely characterized. The ability of autoantibodies to trigger the classical pathway is evident, while the lectin and alternative pathways also seem to be of importance. We studied complement activation in patients treated with imlifidase, which leads to rapid IgG depletion, to elucidate the role of complement in anti-GBM disease. The GOOD-IDES-01 trial included 15 anti-GBM disease patients treated with one dose of imlifidase in addition to standard therapy with 6 months of follow-up. Plasma samples were analyzed for C3, C4 and complement activation products [C4d, C3bBbP and soluble terminal complement complexes (sTCC)]. Ratios of C4d/C4 and C3bBbP/C3 were calculated to correct for plasmapheresis. Serum samples were analyzed for anti-drug antibodies (ADA) directed against imlifidase. The C4d/C4 ratio decreased rapidly from its pre-dose level, while sTCC decreased more slowly. sTCC and C3bBbP/C3 were above the reference level throughout the trial. We observed a transient increase in C4d/C4 and C3bBbP/C3, but not sTCC, immediately following treatment with imlifidase, which tended to be more pronounced in patients with more pre-existing ADA. Classical pathway activation decreased rapidly after autoantibody removal by imlifidase and increased again in most of those that experienced a rebound, but terminal complement activation remained elevated throughout the trial. However, due to the small sample size our results must be interpreted with caution.
2025-10-01 | #2566 Urinary markers of inflammation and damage in anti-GBM disease before and after treatment with Imlifidase
Abstract Background and Aims Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease presenting with rapidly progressive glomerulonephritis and in some cases also lung hemorrhages. Urinary markers of inflammation and damage are of great interest as they could present easily accessible information about prognosis with the possibility of repeated measurements to monitor disease progression and response to treatment. However, despite the large number of known urinary markers, the potential in clinical practice remains largely unknown. Imlifidase is a new treatment option in anti-GBM disease for rapid removal of autoantibodies and showed promising results in the phase II trial GOOD-IDES-01. Method In that trial, 15 anti-GBM patients from five European countries were treated with a single dose of imlifidase in addition to standard treatment and monitored for six months. Urine samples from these patients and 28 healthy controls were analyzed for urinary markers already in clinical use (creatinine, albumin, IgG, κ, λ and protein HC), measured at the Department of Clinical Chemistry, Skåne University Hospital, Lund, Sweden, and preclinical markers of renal damage and inflammation (KIM-1, Clusterin, Ngal, sCD163 and MCP-1), measured using ELISA. All markers were corrected for U-creatinine. Results We found that all measured urinary markers were elevated in the anti-GBM patients as compared to established reference values or healthy controls, and though all markers decreased during the trial, they remained elevated at the end of the trial in most patient (Fig. 1). We saw trends to higher levels of albumin, IgG, protein HC, κ, λ, clusterin, Ngal, sCD163 and MCP-1 in patients where anti-GBM autoantibodies rebounded 5–21 days after removal by imlifidase (Fig. 2). Conclusion In conclusion, in our study the urinary markers indicate both glomerular and tubular inflammation and damage which despite improvement persists for six months in patients with anti-GBM disease. Furthermore, patients with a rebound of anti-GBM autoantibodies displayed a tendency to have elevated levels of several urinary markers. These urinary markers could therefore help predict in which patients rebound is likely to occur to allow for adaptation of treatment strategies.
2025-10-01 | Diagnostic Dilemma: When Pyelonephritis Masks Anti-GBM Disease
Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare, rapidly progressive vasculitis targeting type IV collagen in glomerular and alveolar capillaries. While viral infections, smoking, and hydrocarbon exposure have been implicated, their pathogenic role remains unclear. We present a case of a young female with an atypical presentation of anti-GBM disease initially diagnosed as pyelonephritis. Case Description: A 37-year-old woman with no significant medical history presented with lower abdominal discomfort and dark urine. Her only recent exposure was a COVID booster vaccine three months prior. Physical exam revealed left costovertebral angle tenderness. CT abdomen showed left-sided pyelonephritis without hydroureteronephrosis. Urine culture confirmed complicated UTI, and treated with intravenous fluids and antibiotics. Despite therapy, creatinine worsened from 4.0 to 7.0 mg/dL. On day 5, she developed mild hemoptysis without respiratory distress. CT chest revealed bilateral pleural effusions and ground-glass opacities. Anti-GBM antibody titers were >8.0. Kidney biopsy revealed 100% crescentic glomerulonephritis with fibrinoid necrosis and linear IgG staining on immunofluorescence. Treated with pulse-dose methylprednisolone followed by tapering dose, plasmaphoresis and rituximab. She was discharged on prophylactic antimicrobials and a proton pump inhibitor. She remained dialysis-dependent at 3-month follow-up. Renal transplant counseling was initiated, contingent on pulmonary resolution and sustained anti-GBM seronegativity. Discussion: The nature of this systemic disorder illustrates the diagnostic challenge of anti-GBM disease mimicking infection, leading to misdiagnosis as pyelonephritis despite no traditional risk factors. Worsening AKI despite appropriate therapy should prompt additional vasculitis evaluation, as delayed recognition contributes to poor renal outcomes. While plasmapheresis, steroids, and cyclophosphamide are standard therapy, rituximab was chosen due to gonadotoxic concerns, highlighting individualized treatment approaches. Emerging therapies like Imlifidase offer potential renal benefit, reinforcing the importance of early diagnosis in atypical presentations. Although the patient received a COVID booster vaccination three months ago, no causal association has been described in the literature.
other
2025-04-29 | Deletion of HIF-2α in Dendritic Cells Attenuates Anti-Glomerular Basement Membrane Nephritis.
Background: Anti-glomerular basement membrane (anti-GBM) nephritis is mediated by autoantibodies and may progress to end-stage renal disease. Although its pathogenesis is not completely understood, dendritic cells (DCs) have been reported to play an important role in this process. Hypoxia-inducible factor-2α (HIF-2α) has been reported to have a regulatory effect on DCs under hypoxic conditions, while no research has investigated its role in autoimmune nephritis. Methods: Anti-GBM nephritis was induced in CD11c-specific HIF-2α-deficient and WT mice using nephrotoxic serum (NTS). All mice were divided into four groups: (i) WT+PBS, (ii) CD11c-Cre+ Hif2αfl/fl+PBS, (iii) WT+NTS and (iv) CD11c-Cre+ Hif2αfl/fl+NTS. Seven days after induction, renal function, immune cell infiltration and the expression levels of genes in the renal cortex were assessed in each group. Results: On day 7, the levels of serum creatinine and blood urea nitrogen and the urine albumin-to-creatinine ratio were lower for mice with DC-specific deletion of HIF-2α compared with their WT counterparts (p < 0.05). Histopathological analysis showed that there was less crescent formation in the renal cortex with conditional HIF-2α knockout, and the infiltration of DCs and macrophages was also suppressed (p < 0.05). Genes related to antigen processing and presentation were found to be expressed differentially between the two groups, and the activation of the MAPK pathway was affected (p < 0.05). Western blot analysis validated that HIF-2α knockout inhibited the phosphorylation of p38 MAPK (p < 0.05). Conclusions: In this study, we observed a pro-inflammatory effect of HIF-2α in DCs in early anti-GBM nephritis, and the results suggested a regulating effect of HIF-2α on p38 MAPK pathways.
2024-09-03 | Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice.
Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.
2021-01-15 | Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of glomerulonephritis.
Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.
2018-01-12 | Production and Analysis of Conditional KO Mice of CCN2 in Kidney.
CCN2 has been shown to be closely involved in the progression of renal fibrosis, indicating the potential of CCN2 inhibition as a therapeutic target. Although the examination of the phenotypes of adult CCN2 knockout mice with renal diseases has yielded valuable scientific insights, perinatal death has limited studies of CCN2 in vivo. Conditional knockout technology has become widely used for the deletion of genes in the desired cell populations and time points through the use of cell-specific Cre recombinase-expressing mice. Accordingly, several lines of CCN2 floxed mice have been developed for the assessment of the functional role of CCN2 in adult mice.CCN2 levels are increased in renal fibrosis and proliferative glomerulonephritis, which represent good disease models for evaluating the effects of CCN2 deletion on the kidney. Of these, anti-glomerular basement membrane antibody glomerulonephritis has become the most widely used model for evaluating the effect of increased renal CCN2 expression. Herein, we describe the construction of CCN2 floxed mice and inducible systemic CCN2 conditional knockout mice and methods for the induction of anti-glomerular basement membrane antibody glomerulonephritis.
2004-03-19 | Blockade of TGF-beta action ameliorates renal dysfunction and histologic progression in anti-GBM nephritis.
We tested whether the entire soluble extracellular domain of the human transforming growth factor-beta (TGF-beta) type II receptor, fused to the Fc portion of human immunoglobulin G (IgG1) (Tbeta-ExR) and expressed in skeletal muscles by adenovirus-mediated gene transfer (AdTbeta-ExR), can ameliorate renal dysfunction and histologic progression in a rat experimental anti-glomerular basement membrane (GBM) nephritis. Anti-GBM nephritis was induced in Wistar Kyoto rats by an intravenous injection of anti-rat glomerular basement membrane (GBM) sera. At day 1 (24 hours after induction), AdTbeta-ExR (1 x 109 pfu/mL) was injected into the femoral muscle in the treatment group, and an adenovirus vector-expressing bacterial beta-galactosidase (AdLacZ) was injected into the control group. Then, clinical and histologic changes were examined for 3 weeks after the induction of anti-GBM nephritis. Tbeta-ExR was detected in the serum at day 7, but the serum concentration of Tbeta-ExR had decreased below the detectable level by day 14. Although blood pressure and the degree of proteinuria were similar in both groups, the deterioration of renal function was significantly blunted in the treatment group. Crescent formation and interstitial fibrosis were also ameliorated in the treatment group. These histologic improvements were accompanied by the decreased interstitial infiltration of macrophages and the decreased alpha-smooth muscle actin (alpha-SMA)-positive cells in the glomeruli and the interstitium. This study demonstrated for the first time that the blockade of TGF-beta action by AdTbeta-ExR in the early stage of anti-GBM nephritis ameliorates the clinical and histologic progression. In addition, this study shed light on the development of a specific gene therapy for human crescentic glomerulonephritis.
cell therapies
2026-09-23 | Outcomes of intensive care patients with acute small-vessel vasculitis: a 23-year single-centre experience.
Patients with fulminant small-vessel vasculitis (SVV) may require intensive care unit (ICU) admission, where mortality is high. We describe outcomes and prognostic factors in ICU patients with ANCA-associated vasculitis (AAV) and anti-glomerular basement membrane (anti-GBM) disease over a 23-year period. Patients admitted with acute manifestations of new or flaring AAV or anti-GBM disease were identified from our hospital ICU database (1999-2022). Patients treated solely in high-dependency areas were excluded. Primary outcomes were mortality at 30 and 90 days and development of end-stage kidney disease (ESKD). A matched case-control analysis (1:4) adjusted for age, gender, APACHE II score and admission year was performed for a patient subgroup. 85 cases (82% AAV, 15% anti-GBM) were identified, 80% newly diagnosed. Median APACHE II score was 19. Ventilatory support and continuous venovenous haemodiafiltration were required in 92% and 66% of cases, respectively. 30-day and 90-day mortality rates were 15% and 26%, respectively. Among 90-day survivors, 17 (28%) developed new ESKD. Vasculitis treatments included cyclophosphamide (59%), rituximab (53% of AAV patients) and plasma exchange (71%). These treatments were associated with 90-day and long-term survival. Treatment for vasculitis post-2008 was associated with 90-day and long-term survival, which was not mirrored in ICU controls. This coincided with improvements to the vasculitis service and therapeutic strategies. This single-centre study reports ICU outcomes for patients with fulminant SVV over 23 years. 30 and 90-day ICU mortality were comparable with other reported values. Improvement in mortality was associated with changes in vasculitis treatment protocols.
2026-08-22 | Concurrent Anti-glomerular Basement Membrane (Anti-GBM) Disease and Immunoglobulin A Nephropathy (IgAN) Presenting With Severe Pulmonary-Renal Syndrome: A Case Report.
Anti-glomerular basement membrane (anti-GBM) disease is a rare, aggressive autoimmune condition that typically presents as rapidly progressive glomerulonephritis and can be complicated by pulmonary haemorrhage. The co-occurrence of anti-GBM disease and IgA nephropathy (IgAN) is extremely uncommon, though increasingly recognised as a distinct clinical and pathological entity. We describe a 51-year-old Sudanese man who presented with acute hypoxaemic respiratory failure, haemoptysis, severe anaemia, and acute kidney injury. Testing showed high levels of anti-GBM antibodies, with negative anti-neutrophil cytoplasmic antibodies. Chest imaging revealed diffuse alveolar haemorrhage. Renal biopsy demonstrated crescentic glomerulonephritis with linear IgG staining along the glomerular basement membrane, alongside mesangial deposits dominated by IgA, confirming the presence of both diseases. Treatment included plasma exchange, high-dose corticosteroids, cyclophosphamide, and bronchial artery embolisation, which led to significant respiratory improvement and stabilisation of kidney function. A review of published cases suggests that individuals with this overlap may experience better renal outcomes than those with anti-GBM disease alone, though serious pulmonary-renal symptoms can still occur. This case highlights the need for accurate clinicopathological assessment and prompt initiation of anti-GBM-specific treatment.
2026-06-02 | Role of therapeutic plasma exchange (TPE) in the management of anti-glomerular basement membrane (anti-GBM) disease: A case series from tertiary-care hospital in India
Abstract: INTRODUCTION: Anti-glomerular basement membrane (anti-GBM) disease is an uncommon, autoimmune disease in which IgG antibodies bind to intrinsic antigens distributed along the length of glomerular basement membrane. It is characterized by rapid and progressive loss of renal function. The rationale of management is to suppress renal inflammation and production of autoantibodies (with immunosuppression), as well as removal of circulating pathogenic autoantibodies (with therapeutic plasma exchange [TPE]). However, there is a paucity of data on the role of TPE in the management of anti-GBM cases worldwide. MATERIALS AND METHODS: Three consecutive anti-GBM patients were admitted with common complaints of high-grade fever, chills, hematuria, and low urine output. In view of decreased renal function and strong suspicion of anti-GBM disease, the treatment protocol was initiated in accordance with the international Kidney Disease Improving Global Outcomes guidelines. RESULTS: All three patients had crescentic glomerulonephritis (crescents in more >80% glomeruli) on renal biopsy. Management was initiated with TPE and immunosuppression (methylprednisolone) and cytotoxic drug (cyclophosphamide). TPE was done until the anti-GBM antibody titer dropped to <10. Case 1 underwent TPE daily (12 sessions), and case 2 and case 3 underwent 14 and 9 sessions, respectively, of TPE alternating with dialysis. Renal function improved in cases 1 and 2, and routine dialysis was discontinued. Case 3 showed improvement initially until TPE was done; however, the disease progressed to end-stage renal disease, and the patient remains dialysis dependent. None of the patients had adverse reactions during TPE. CONCLUSION: TPE is an effective and safe conjunct in the treatment of anti-GBM disease as shown by complete reversal in two cases and partial response in the third patient.
2026-05-01 | C41-07 A Rare Case of Diffuse Alveolar Hemorrhage From Dual Positive Goodpasture Syndrome
Abstract Diffuse Alveolar Hemorrhage (DAH) is a life-threatening pulmonary emergency with the most common cause being a small-vessel vasculitis, such as ANCA-associated vasculitis (AAV) or anti-GBM vasculitis (Goodpasture syndrome). Concurrent positivity for both AAV and anti-GBM antibodies is rare but often signifies a more severe presentation and greater therapeutic challenge. A 53-year-old gentleman with no significant past medical history or oxygen requirement at baseline presented to the ED with one day of acute massive hemoptysis, dyspnea, and hypoxic respiratory failure requiring oxygen supplementation. Physical exam was notable for diffuse crackles bilaterally. Recent history was significant for hospitalization a month ago for new onset hematuria and an AKI, as well as an episode of hemoptysis. Kidney biopsy done at that time showed crescentic glomerulonephritis with positive anti-GBM, and serum studies showed positive PR3 ANCA antibodies at high titers. The patient was managed with pulse dose steroids, plasma exchange (PLEX), and rituximab, but missed a dose of scheduled Rituximab outpatient. CT scan showed bilateral patchy infiltrates (Image 1), concerning for DAH. A bronchoscopy with bronchoalveolar lavage showed washings with progressive bloody appearance, consistent with DAH. With rheumatology on board, the patient was diagnosed with AAV and Goodpasture syndrome overlap and treated with 5 sessions of plasma exchange, pulse-dose glucocorticoids, and one dose of cyclophosphamide. After his first session of plasma exchange and initiation of steroids, the patient’s hypoxemia resolved. After a two-week stay, the patient was discharged on a prednisone taper with a plan to continue cyclophosphamide outpatient. This case highlights a rare but clinically significant etiology of DAH—dual positive Goodpasture syndrome. This diagnosis is not only rare, but also associated with high mortality. A potential pathophysiology is AAV-associated damage to the glomerular basement membrane, leading to uncovering “hidden antigens” from the membrane and inducing the formation of antibodies. Classic treatment for AAV is glucocorticoids with rituximab or cyclophosphamide, whereas for Goodpasture is PLEX and immunosuppressive therapy. Dual-positive disease lies on a continuum between AAV and Goodpasture syndrome but behaves distinctly, often presenting with recurrent or refractory manifestations. Unlike isolated AAV or Goodpasture disease, management requires combining therapeutic principles from both. For this patient with dual disease, the key to successful management involved both PLEX and steroid therapy. This case emphasizes the importance of initial high suspicion for DAH in patients with hemoptysis, respiratory failure, and history of vasculitis. Also, dual-positive anti-GBM vasculitis exists and demands a tailored, hybrid treatment approach. This abstract is funded by: None
2026-02-03 | Plasma Exchange for Anti-GBM Disease With Dialysis Dependency: A Case Series on Clinical Outcomes and Safety.
The efficacy of plasma exchange (PEx) in patients with anti-glomerular basement membrane antibody (anti-GBM Ab) disease requiring renal replacement therapy (RRT) at diagnosis remains unclear. This study aimed to investigate the outcomes and safety of patients with uremic anti-GBM Ab disease undergoing PEx. We retrospectively analyzed nine patients confirmed by renal biopsy who received PEx using fresh frozen plasma or 5% human albumin solution and underwent hemodialysis (HD) concomitantly with standard immunosuppressive therapy. The outcome was determined as dialysis dependency, and safety was evaluated for adverse events. Two patients (22.2%) achieved dialysis independence at 10 and 11 months. Both patients had relatively preserved normal glomeruli (15.8%-37.2%) and achieved early remission. Retroperitoneal hemorrhage and recalcitrant anti-GBM Ab were noteworthy in other cases. PEx can facilitate renal recovery in selected patients with anti-GBM disease requiring RRT. Pathological evaluation may be useful to determine the intensity and duration of treatment, including PEx.
small molecules
2026-09-04 | HIF-1α regulates ADAM9 expression in Th17 cells during autoimmune disease.
Hypoxia-inducible factor 1α (HIF-1α) promotes T helper 17 (Th17) differentiation, but whether it regulates ADAM9 expression in Th17 cells during autoimmune nephritis remains unclear. Hypoxia enhanced Th17 differentiation and increased ADAM9 expression in a HIF-1α-dependent manner. HIF-1α deficiency reduced ADAM9 expression and impaired Th17 differentiation in vitro. In anti-glomerular basement membrane nephritis and B6.lpr lupus-prone mice, T cell-specific HIF-1α deletion attenuated renal pathology and reduced kidney-infiltrating CD4+ and IL-17A-producing T cells. These findings identify ADAM9 as a HIF-1α-regulated target in Th17 cells that may contribute to autoimmune renal inflammation.
2026-06-08 | Concurrent anti-GBM disease and p-ANCA vasculitis presenting as pulmonary-renal syndrome in a patient with chronic kidney disease: a case report.
The coexistence of anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis represents a rare autoimmune overlap syndrome that poses significant diagnostic and therapeutic challenges. This dual-positive presentation is particularly uncommon in patients with pre-existing chronic kidney disease (CKD) and offers valuable insight into the complexities of disease overlap and management. We report a 48-year-old woman with known CKD who presented with acute pulmonary-renal syndrome manifesting as dyspnea, productive cough, oliguria, and altered sensorium. Laboratory evaluation revealed markedly elevated serum urea and creatinine, raised inflammatory markers, and dual serologic positivity for anti-GBM and perinuclear ANCA (p-ANCA) antibodies, confirming dual-positive vasculitis. Serologic testing was initiated due to persistent respiratory distress and worsening renal function despite appropriate hemodialysis and empiric antibiotic therapy, prompting evaluation for an underlying autoimmune etiology. Testing was performed within the first 48 h of admission after failure of initial supportive measures to produce clinical improvement. The patient received urgent hemodialysis, high-dose intravenous corticosteroids followed by oral taper, plasmapheresis, and cyclophosphamide. Her neurological and respiratory symptoms improved gradually; however, dialysis dependence persisted due to underlying renal damage. Dual-positive anti-GBM and ANCA-associated vasculitis represents an uncommon but clinically significant overlap syndrome. The coexistence of both antibodies complicates diagnosis and management, especially in patients with CKD, where baseline renal dysfunction may mask active disease. Early recognition through serologic testing and prompt initiation of combined immunosuppressive and plasmapheresis therapy are critical to preventing irreversible organ injury. This case reinforces the importance of multidisciplinary management and long-term follow-up to monitor disease activity and prevent relapse. This case highlights the need to consider dual-positive anti-GBM and ANCA-associated vasculitis in patients presenting with unexplained renal deterioration or pulmonary symptoms, even in the context of CKD. Timely diagnosis and individualized immunosuppressive therapy can improve outcomes and reduce irreversible organ damage in this rare overlap syndrome.
2026-06-03 | Anti-Glomerular Basement Membrane Disease Combined with IgA Nephropathy: A Case Report and Literature Review.
Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease characterized by injury to small blood vessels in the kidneys and/or lungs. IgA nephropathy is the most common primary glomerular disease diagnosed in China. However, the co-occurrence of anti-GBM illness and IgA nephropathy has been infrequently documented in the literature. At present, its mechanism is unknown, the treatment approach is unclear, and the prognosis remains poor. Herein, we report a case of anti-GBM disease complicated with IgA nephropathy, in which renal function returned to normal state following treatment with a combination of prednisone and cyclophosphamide. This case suggests that in patients with anti-GBM disease and IgA nephropathy, the combination of glucocorticoids and cyclophosphamide may serve as an optimum treatment choice.
2026-05-13 | A case report of concomitant anti-glomerular basement membrane disease, IgA nephropathy, and membranous nephropathy.
The coexistence of anti-glomerular basement membrane (anti-GBM) disease, IgA nephropathy (IgAN), and membranous nephropathy (MN) represents an exceptionally rare glomerular pathology triad, with only one previously documented case. This study explores the underlying mechanisms linking these distinct entities and reports a novel case associated with persistent elevation of serum amylase and lipase, thereby expanding the clinical spectrum of this complex disease combination. A 51-year-old woman presenting with recurrent macroscopic hematuria and rapidly progressive renal dysfunction was diagnosed with simultaneous triple glomerulopathy based on positive anti-GBM antibodies and renal biopsy findings. An integrated therapeutic regimen was administered, including high-dose methylprednisolone pulse therapy, cyclophosphamide, intensive plasma exchange (PE), and hemodialysis. Treatment led to undetectable anti-GBM antibody titers within two months, successful discontinuation of hemodialysis by the third month, and complete resolution of hematuria. By the ten-month follow-up, proteinuria and serum creatinine levels significantly decreased, renal function stabilized with normal urine output, and no significant adverse events were observed. This case demonstrates the pathological coexistence of triple glomerulopathy. Although clinical improvement was observed after a combined regimen of early PE and immunosuppression, causality cannot be inferred from a single case. These findings provide hypothesis-generating insights for the management of similar complex cases and highlight the need for further research.
2026-04-06 | De novo antiglomerular basement membrane Goodpasture syndrome in a liver transplant recipient: balancing autoimmunity, allograft protection, and infection risk.
Antiglomerular basement membrane (anti-GBM) disease causes rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage (DAH) through autoantibodies directed against the α3 chain of type IV collagen. Evidence guiding adaptation of standard induction therapy (plasmapheresis, high-dose glucocorticoids, cyclophosphamide) for nonrenal solid organ transplant recipients remains scarce. A 55-year-old man, 9 years post-deceased donor liver transplantation for nonalcoholic steatohepatitis and maintained on low-dose tacrolimus, presented with pulmonary renal syndrome, severe metabolic acidosis, and high-titer anti-GBM antibodies. High-resolution computed tomography demonstrated bilateral ground-glass opacities consistent with DAH. He was treated with plasma exchange (seven sessions) and high-dose corticosteroids. Tacrolimus was discontinued, and maintenance immunosuppression was transitioned to mycophenolate mofetil with low-dose prednisone. Pulmonary hemorrhage resolved and anti-GBM titers declined to near the assay threshold; however, kidney function did not recover, and he remained dependent on hemodialysis. Four months later, he died of multidrug-resistant Acinetobacter pneumonia complicated by septic shock. To our knowledge, this represents the first reported case of de novo anti-GBM disease following liver transplantation. De novo Goodpasture syndrome can occur despite chronic immunosuppression in liver transplant recipients. Prompt recognition, individualized immunomodulation, and meticulous infection risk management are critical to controlling autoimmunity while preserving liver allograft function.
antibodies
2026-09-09 | Efficacy and safety of eculizumab-combined therapy for patients with anti-GBM disease.
The study aimed to evaluate the efficacy and safety of eculizumab in addition to conventional therapy for anti-glomerular basement membrane (anti-GBM) disease presenting rapidly progressive glomerulonephritis (RPGN). 42 patients with anti-GBM disease presenting with RPGN were included in this multicenter retrospective cohort study. All patients received intensive immunosuppressive therapy including intravenous methylprednisolone pulses followed by maintenance prednisone, in combination with at least two of the following: intravenous cyclophosphamide, therapeutic plasma apheresis, rituximab, or eculizumab. The cohort was stratified into two groups: the eculizumab group (n = 13) which received eculizumab (900 mg once weekly for 1-5 doses) in combination with other therapies, and the control group (n = 29) which did not receive eculizumab. Kidney survival at 12 weeks and 24 weeks, and adverse events (infections, metabolic alterations, laboratory abnormalities), ascertained via clinical and laboratory data. At 12 weeks, the eculizumab group showed significantly higher kidney survival compared with the control group (69.2% vs. 31.0%, p = 0.021). At 24 weeks, kidney survival remained numerically higher in the eculizumab group (66.7% vs. 40.7%, p = 0.081). Kaplan-Meier curves for renal survival by the Gehan-Breslow-Wilcoxon test, which places greater emphasis on early events, revealed a statistically significant difference between the groups (χ² = 4.137; p = 0.042); however, the difference assessed by the log-rank test did not reach statistical significance (χ² = 3.491; p = 0.062). There were no significant differences in the overall incidence of infections or other adverse events. Combined therapy with eculizumab showed improved early kidney survival for anti-GBM nephritis at 12 weeks, and did not increase the risk of adverse events. Prospective, large-sample studies with long-term follow-up are needed to validate its efficacy and safety.
2026-08-19 | Anti-glomerular basement membrane disease: A contemporary case series from a large university hospital center.
Anti-glomerular basement membrane disease (anti-GBM) is a rare autoimmune disorder characterized by autoantibodies targeting antigens in the glomerular and alveolar basement membranes, often leading to rapidly progressive glomerulonephritis and pulmonary hemorrhage. Contemporary real-world data on clinical presentation and long-term renal outcomes remain scarce. This study aims to examine the clinical and pathological features, as well as renal survival and long-term outcomes, in patients with anti-GBM disease. Retrospective single-center case series. All patients diagnosed with anti-GBM disease at a major Portuguese university hospital between 2003 and 2023 were included. Anti-GBM disease was defined as a compatible clinical presentation plus positive anti-GBM antibodies in circulation and/or biopsy-proven anti-GBM disease. Demographic, clinical, laboratory and therapeutic data were reviewed. Twenty-seven patients were included (mean age 58.7±22.0 years; 59.3% female). Renal involvement was universal and severe (mean serum creatinine 11.95±10.18mg/dL), with 92.6% requiring renal replacement therapy (RRT) at presentation. Alveolar hemorrhage occurred in 33.3% patients. Anti-GBM antibodies were detected in 92.6%; 29.6% were also ANCA-positive. Kidney biopsy (n=15) showed crescentic glomerulonephritis in 80% with a mean crescent burden of 60.9% and a median of 0% normal glomeruli (IQR 0-1). Most patients (92%) received immunosuppressive therapy, and 68% were treated with the standard combination of corticosteroids, cyclophosphamide, and plasma exchange. Renal recovery was limited: only 5 patients (18.5%) who required RRT at presentation recovered renal function, and 66.7% progressed to end-stage kidney disease (ESKD). Higher baseline serum creatinine, a lower proportion of normal glomeruli, and crescentic involvement >40% were significantly associated with ESKD. One- and five-year patient survival were 85.2% and 74.1%, respectively. No relapses occurred. Anti-GBM disease in this Portuguese cohort presented predominantly with severe acute kidney injury requiring RRT and was associated with poor renal recovery despite guideline-directed therapy. Histologic preservation of normal glomeruli and baseline kidney function were strongly associated with renal outcomes. These findings underscore the need for earlier recognition and timely referral, as well as the development of more effective targeted therapies for this severe glomerular disease.
2026-08-19 | Anti-Glomerular Basement Membrane Antibody Disease Complicated by Complement-Mediated Thrombotic Microangiopathy: A Case Report.
Anti-glomerular basement membrane (GBM) antibody disease rarely causes thrombotic microangiopathy (TMA). We herein report the case of a 75-year-old Japanese woman who developed refractory TMA during treatment for anti-GBM antibody disease. Although secondary TMA was initially suspected, persistent hemolytic anemia and thrombocytopenia despite plasma exchange, glucocorticoids, and cyclophosphamide led us to suspect complement-mediated TMA. Eculizumab was initiated after genetic testing for complement regulatory factors was performed. The patient became transfusion-independent within one week, and genetic testing identified the c.293C＞T (p.Thr98Ile) variant in CD46. Complement-mediated TMA should thus be considered in refractory cases, and anti-C5 monoclonal antibodies may be an effective therapeutic option.
2026-08-01 | Age-Related Differences in Anti-GBM Disease: Distinct Biology or Distinct Timing of Presentation?
We read with great interest the multicenter European study by Suhlrie et al.1 comparing outcomes in pediatric and adult anti-glomerular basement membrane (anti-GBM) disease. The study provides valuable contemporary data in a rare disorder and highlights important age-related differences in presentation and outcomes.
2026-07-07 | Immunological overlap stratification in anti-GBM disease: prognostic differences and serological correlations—a single-center retrospective cohort study
Background Anti-glomerular basement membrane (anti-GBM) disease is not a distinct, isolated entity but rather a condition that frequently overlaps with other autoimmune serological profiles. Most notably, it can coexist with antineutrophil cytoplasmic antibodies (ANCA), alongside a diverse spectrum of additional autoantibodies. Despite the occurrence of such antibody overlap in a subset of patients, their specific clinical manifestations and prognostic implications remain poorly defined and largely elusive. Methods This study retrospectively enrolled patients diagnosed with anti-GBM disease at the First Affiliated Hospital with Nanjing Medical University between January 2017 and January 2024. Based on serological profiles, enrolled patients were stratified into three cohorts: the classic anti-GBM group (anti-GBM antibodies positive alone), the ANCA-anti-GBM double-positive group, and the anti-GBM-non-ANCA autoantibody overlap group. Clinical, pathological, treatment, and outcome characteristics were systematically compared across the three groups. Additionally, landmark analysis was conducted to assess prognostic discrepancies across distinct time intervals. Results A total of 67 patients with anti-GBM disease were enrolled in this study, with 30, 18, and 19 cases allocated to the classic anti-GBM group, ANCA-anti-GBM double-positive group, and anti-GBM-non-ANCA autoantibody overlap group, respectively. The ANCA-anti-GBM double-positive group presented with the highest mean age at onset among the three cohorts. A statistically significant difference was detected in baseline anti-GBM antibody titers across the groups (median: 141.20 vs. 104.25 vs. 181.70; interquartile range: 102.90–257.70 vs. 52.15–137.07 vs. 121.05–555.40; p = 0.044). By contrast, no significant differences were noted in terms of other clinical characteristics, renal pathological findings, and therapeutic regimens. Although the overall survival rates showed no statistical discrepancy among the three groups, distinct trends were observed in early survival outcomes: the ANCA-anti-GBM double-positive group had the poorest early survival, followed by the anti-GBM-non-ANCA autoantibody overlap group, while the classic anti-GBM group exhibited the most favorable early survival profile. Conclusion This study identifies the distinct phenotypic traits of anti-GBM disease with concurrent other autoimmune antibodies, underscoring that sole reliance on anti-GBM antibody titers is inappropriate for prognostic judgment and treatment decision-making. For patients with anti-GBM disease overlapping with non-ANCA autoantibodies, intensive treatment regimens may be justified to achieve more favorable clinical prognosis.
proteins
2026-06-12 | Butyric Acid-Modified m-P14 Peptide Ameliorates Anti-Glomerular Basement Membrane Disease.
The non-collagenous domain 1 of the α3 chain of type IV collagen (α3(IV)NC1) is the primary autoantigen in anti-glomerular basement membrane (anti-GBM) disease. We previously developed a modified antigen-specific peptide, m-P14, derived from the nephritogenic epitope α3127-148, which ameliorated experimental anti-GBM nephritis. However, its short half-life limits clinical translation. This study evaluated a butyrate-conjugated derivative (m-P14-BA) to improve pharmacokinetic properties while preserving therapeutic efficacy. M-P14-BA and m-P14 were administered to α3127-148 immunized Wistar Kyoto rats in early and late treatment settings. Renal injury parameters and intrarenal inflammation were assessed, and pharmacokinetic profiles were evaluated following intraperitoneal administration in beagle dogs. M-P14-BA reduced proteinuria, crescent formation, glomerular IgG deposition, complement activation, and inflammatory cell infiltration, with overall efficacy comparable to m-P14 in early treatment settings. In late treatment settings, m-P14-BA was associated with a significant improvement in blood urea nitrogen levels and modest reductions in proteinuria and histopathological injury. Butyrate conjugation markedly improved pharmacokinetics, prolonging plasma elimination half-life by approximately 2.8-fold and increasing systemic exposure nearly fourfold. These pharmacokinetic improvements were associated with maintained therapeutic efficacy at a reduced dose, with 10 mg/kg m-P14-BA achieving effects broadly similar to those observed with 30 mg/kg m-P14. In summary, butyrate conjugation improves the pharmacokinetic profile of an antigen-specific therapeutic peptide while preserving therapeutic activity, suggesting a potential strategy to enhance the translational feasibility of peptide-based immunotherapy in anti-GBM disease.
2026-04-20 | Antiglomerular Basement Membrane Antibody-Associated Rapidly Progressive Glomerulonephritis in a Patient With Chromosome 10p Deletion
Anti-glomerular basement membrane antibodies cause rapidly progressive glomerulonephritis that regularly results in anuric, end stage kidney disease. Disruption of collagen structure can precipitate its onset. We here report the case of a 22-year-old man with severe disability due to chromosome 10p12 deletion who presented with anuric renal failure. Renal histology yielded severe crescentic glomerulonephritis, anti-glomerular basement antibodies were positive. Therapy with plasmapheresis, steroid pulse therapy and six courses of cyclophosphamide was complicated by severe anemia and nausea with vomiting. After six months, despite severe CKD, dialysis free life and vivacity undiscernible from his pre-glomerulonephritis state was achieved. The case underlines the importance of individualized patient care. Immunologic relevance of the fibrosis-modifying negative TGF-beta modulator "BMP and Activin Membrane-Bound Inhibitor (BAMBI), localized on chromosome 10p12, may be of interest.
2026-01-12 | Complement activation in anti-glomerular basement membrane disease before and after treatment with imlifidase.
The involvement of the complement system in anti-glomerular basement membrane (GBM) disease is well known but incompletely characterized. The ability of autoantibodies to trigger the classical pathway is evident, while the lectin and alternative pathways also seem to be of importance. We studied complement activation in patients treated with imlifidase, which leads to rapid IgG depletion, to elucidate the role of complement in anti-GBM disease. The GOOD-IDES-01 trial included 15 anti-GBM disease patients treated with one dose of imlifidase in addition to standard therapy with 6 months of follow-up. Plasma samples were analyzed for C3, C4 and complement activation products [C4d, C3bBbP and soluble terminal complement complexes (sTCC)]. Ratios of C4d/C4 and C3bBbP/C3 were calculated to correct for plasmapheresis. Serum samples were analyzed for anti-drug antibodies (ADA) directed against imlifidase. The C4d/C4 ratio decreased rapidly from its pre-dose level, while sTCC decreased more slowly. sTCC and C3bBbP/C3 were above the reference level throughout the trial. We observed a transient increase in C4d/C4 and C3bBbP/C3, but not sTCC, immediately following treatment with imlifidase, which tended to be more pronounced in patients with more pre-existing ADA. Classical pathway activation decreased rapidly after autoantibody removal by imlifidase and increased again in most of those that experienced a rebound, but terminal complement activation remained elevated throughout the trial. However, due to the small sample size our results must be interpreted with caution.
2025-10-01 | #2566 Urinary markers of inflammation and damage in anti-GBM disease before and after treatment with Imlifidase
Abstract Background and Aims Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease presenting with rapidly progressive glomerulonephritis and in some cases also lung hemorrhages. Urinary markers of inflammation and damage are of great interest as they could present easily accessible information about prognosis with the possibility of repeated measurements to monitor disease progression and response to treatment. However, despite the large number of known urinary markers, the potential in clinical practice remains largely unknown. Imlifidase is a new treatment option in anti-GBM disease for rapid removal of autoantibodies and showed promising results in the phase II trial GOOD-IDES-01. Method In that trial, 15 anti-GBM patients from five European countries were treated with a single dose of imlifidase in addition to standard treatment and monitored for six months. Urine samples from these patients and 28 healthy controls were analyzed for urinary markers already in clinical use (creatinine, albumin, IgG, κ, λ and protein HC), measured at the Department of Clinical Chemistry, Skåne University Hospital, Lund, Sweden, and preclinical markers of renal damage and inflammation (KIM-1, Clusterin, Ngal, sCD163 and MCP-1), measured using ELISA. All markers were corrected for U-creatinine. Results We found that all measured urinary markers were elevated in the anti-GBM patients as compared to established reference values or healthy controls, and though all markers decreased during the trial, they remained elevated at the end of the trial in most patient (Fig. 1). We saw trends to higher levels of albumin, IgG, protein HC, κ, λ, clusterin, Ngal, sCD163 and MCP-1 in patients where anti-GBM autoantibodies rebounded 5–21 days after removal by imlifidase (Fig. 2). Conclusion In conclusion, in our study the urinary markers indicate both glomerular and tubular inflammation and damage which despite improvement persists for six months in patients with anti-GBM disease. Furthermore, patients with a rebound of anti-GBM autoantibodies displayed a tendency to have elevated levels of several urinary markers. These urinary markers could therefore help predict in which patients rebound is likely to occur to allow for adaptation of treatment strategies.
2025-10-01 | Diagnostic Dilemma: When Pyelonephritis Masks Anti-GBM Disease
Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare, rapidly progressive vasculitis targeting type IV collagen in glomerular and alveolar capillaries. While viral infections, smoking, and hydrocarbon exposure have been implicated, their pathogenic role remains unclear. We present a case of a young female with an atypical presentation of anti-GBM disease initially diagnosed as pyelonephritis. Case Description: A 37-year-old woman with no significant medical history presented with lower abdominal discomfort and dark urine. Her only recent exposure was a COVID booster vaccine three months prior. Physical exam revealed left costovertebral angle tenderness. CT abdomen showed left-sided pyelonephritis without hydroureteronephrosis. Urine culture confirmed complicated UTI, and treated with intravenous fluids and antibiotics. Despite therapy, creatinine worsened from 4.0 to 7.0 mg/dL. On day 5, she developed mild hemoptysis without respiratory distress. CT chest revealed bilateral pleural effusions and ground-glass opacities. Anti-GBM antibody titers were >8.0. Kidney biopsy revealed 100% crescentic glomerulonephritis with fibrinoid necrosis and linear IgG staining on immunofluorescence. Treated with pulse-dose methylprednisolone followed by tapering dose, plasmaphoresis and rituximab. She was discharged on prophylactic antimicrobials and a proton pump inhibitor. She remained dialysis-dependent at 3-month follow-up. Renal transplant counseling was initiated, contingent on pulmonary resolution and sustained anti-GBM seronegativity. Discussion: The nature of this systemic disorder illustrates the diagnostic challenge of anti-GBM disease mimicking infection, leading to misdiagnosis as pyelonephritis despite no traditional risk factors. Worsening AKI despite appropriate therapy should prompt additional vasculitis evaluation, as delayed recognition contributes to poor renal outcomes. While plasmapheresis, steroids, and cyclophosphamide are standard therapy, rituximab was chosen due to gonadotoxic concerns, highlighting individualized treatment approaches. Emerging therapies like Imlifidase offer potential renal benefit, reinforcing the importance of early diagnosis in atypical presentations. Although the patient received a COVID booster vaccination three months ago, no causal association has been described in the literature.
other
2025-04-29 | Deletion of HIF-2α in Dendritic Cells Attenuates Anti-Glomerular Basement Membrane Nephritis.
Background: Anti-glomerular basement membrane (anti-GBM) nephritis is mediated by autoantibodies and may progress to end-stage renal disease. Although its pathogenesis is not completely understood, dendritic cells (DCs) have been reported to play an important role in this process. Hypoxia-inducible factor-2α (HIF-2α) has been reported to have a regulatory effect on DCs under hypoxic conditions, while no research has investigated its role in autoimmune nephritis. Methods: Anti-GBM nephritis was induced in CD11c-specific HIF-2α-deficient and WT mice using nephrotoxic serum (NTS). All mice were divided into four groups: (i) WT+PBS, (ii) CD11c-Cre+ Hif2αfl/fl+PBS, (iii) WT+NTS and (iv) CD11c-Cre+ Hif2αfl/fl+NTS. Seven days after induction, renal function, immune cell infiltration and the expression levels of genes in the renal cortex were assessed in each group. Results: On day 7, the levels of serum creatinine and blood urea nitrogen and the urine albumin-to-creatinine ratio were lower for mice with DC-specific deletion of HIF-2α compared with their WT counterparts (p < 0.05). Histopathological analysis showed that there was less crescent formation in the renal cortex with conditional HIF-2α knockout, and the infiltration of DCs and macrophages was also suppressed (p < 0.05). Genes related to antigen processing and presentation were found to be expressed differentially between the two groups, and the activation of the MAPK pathway was affected (p < 0.05). Western blot analysis validated that HIF-2α knockout inhibited the phosphorylation of p38 MAPK (p < 0.05). Conclusions: In this study, we observed a pro-inflammatory effect of HIF-2α in DCs in early anti-GBM nephritis, and the results suggested a regulating effect of HIF-2α on p38 MAPK pathways.
2024-09-03 | Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice.
Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.
2021-01-15 | Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of glomerulonephritis.
Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.
2018-01-12 | Production and Analysis of Conditional KO Mice of CCN2 in Kidney.
CCN2 has been shown to be closely involved in the progression of renal fibrosis, indicating the potential of CCN2 inhibition as a therapeutic target. Although the examination of the phenotypes of adult CCN2 knockout mice with renal diseases has yielded valuable scientific insights, perinatal death has limited studies of CCN2 in vivo. Conditional knockout technology has become widely used for the deletion of genes in the desired cell populations and time points through the use of cell-specific Cre recombinase-expressing mice. Accordingly, several lines of CCN2 floxed mice have been developed for the assessment of the functional role of CCN2 in adult mice.CCN2 levels are increased in renal fibrosis and proliferative glomerulonephritis, which represent good disease models for evaluating the effects of CCN2 deletion on the kidney. Of these, anti-glomerular basement membrane antibody glomerulonephritis has become the most widely used model for evaluating the effect of increased renal CCN2 expression. Herein, we describe the construction of CCN2 floxed mice and inducible systemic CCN2 conditional knockout mice and methods for the induction of anti-glomerular basement membrane antibody glomerulonephritis.
2004-03-19 | Blockade of TGF-beta action ameliorates renal dysfunction and histologic progression in anti-GBM nephritis.
We tested whether the entire soluble extracellular domain of the human transforming growth factor-beta (TGF-beta) type II receptor, fused to the Fc portion of human immunoglobulin G (IgG1) (Tbeta-ExR) and expressed in skeletal muscles by adenovirus-mediated gene transfer (AdTbeta-ExR), can ameliorate renal dysfunction and histologic progression in a rat experimental anti-glomerular basement membrane (GBM) nephritis. Anti-GBM nephritis was induced in Wistar Kyoto rats by an intravenous injection of anti-rat glomerular basement membrane (GBM) sera. At day 1 (24 hours after induction), AdTbeta-ExR (1 x 109 pfu/mL) was injected into the femoral muscle in the treatment group, and an adenovirus vector-expressing bacterial beta-galactosidase (AdLacZ) was injected into the control group. Then, clinical and histologic changes were examined for 3 weeks after the induction of anti-GBM nephritis. Tbeta-ExR was detected in the serum at day 7, but the serum concentration of Tbeta-ExR had decreased below the detectable level by day 14. Although blood pressure and the degree of proteinuria were similar in both groups, the deterioration of renal function was significantly blunted in the treatment group. Crescent formation and interstitial fibrosis were also ameliorated in the treatment group. These histologic improvements were accompanied by the decreased interstitial infiltration of macrophages and the decreased alpha-smooth muscle actin (alpha-SMA)-positive cells in the glomeruli and the interstitium. This study demonstrated for the first time that the blockade of TGF-beta action by AdTbeta-ExR in the early stage of anti-GBM nephritis ameliorates the clinical and histologic progression. In addition, this study shed light on the development of a specific gene therapy for human crescentic glomerulonephritis.
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Drug Discovery Landscape
3 orphan drug designations for Anti-glomerular basement membrane disease.
3 orphan drug designations for Anti-glomerular basement membrane disease.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
veverimer | other | FDA | — | Renibus Therapeutics Inc. |
Imlifidase [Idefirix] | proteins | EMA | Hansa Biopharma AB | |
Imlifidase | proteins | FDA | Hansa Medical AB |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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