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
689 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:
689 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:
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.
2026-06-29 | Mechanistic Insights and Therapeutic Advances of Anti-Inflammatory Biologics in Immune-Mediated Glomerulonephritis: A Narrative Review.
Immune-mediated glomerulonephritis represents a diverse group of kidney disorders caused by dysregulated immune responses and constitutes a major contributor to chronic kidney disease. Its pathogenesis can be conceptualized as a three-step cascade: aberrant activation of innate immunity through pattern-recognition receptors, inflammasome complexes, and complement pathways; adaptive immune dysregulation characterized by imbalanced B- and T-cell responses and the production of pathogenic autoantibodies; and terminal effector injury involving complement-mediated damage and progressive fibrosis. This narrative review summarizes current advances in anti-inflammatory biologics that intervene at these critical points across a broad spectrum of entities, including IgA nephropathy (IgAN), membranous nephropathy (MN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), minimal change nephropathy (MCN), anti-glomerular basement membrane (anti-GBM) disease, ANCA-associated vasculitis (AAV), and C3 glomerulopathy (C3G). Therapies including cytokine inhibitors targeting TNF-α or IL-6, B-cell-depleting antibodies such as anti-CD20, plasma cell-directed agents, and complement blockers against C5 or Factor B have demonstrated clinical benefits in IgAN, MN, and LN, where evidence from randomized controlled trials supports their efficacy in reducing proteinuria and preserving renal function. For other entities such as FSGS, MCN, anti-GBM disease, and C3G, the evidence remains preliminary, based largely on case reports, preclinical models, or early-phase trials. Despite therapeutic advances, challenges persist regarding efficacy variability, infection risks, and financial burden. Future research aims to achieve precision therapy through multi-omics-based stratification, next-generation biologics such as bispecific antibodies and gene therapies, and optimized drug delivery systems, steering immune-mediated glomerulonephritis management toward truly disease-modifying treatment.
2026-06-26 | In Vivo Efficacy of an Inhibitor of Complement and FcRn in Models of Glomerulonephritis and Collagen-Induced Arthritis Using Human C2 Knock-In Mice.
A therapeutic antibody, CSL305, has been developed, which combines inhibition of the complement classical and lectin pathways via complement C2 binding with an ability to act as an antagonist of the neonatal Fc receptor (FcRn). CSL305 binds to human C2 (huC2) but shows no binding or activity against mouse C2 precluding its use in mouse models of disease to fully assess in vivo efficacy. To circumvent this, a mouse strain was developed that replaced the expression of mouse C2 with huC2 by homologous recombination. These mice (huC2 "knock-in"; KI) were shown to express huC2 protein and to have complement activity. Interestingly, male huC2-KI mice showed much stronger complement activity compared to female mice and were also sensitive to inhibition by CSL305. Two models of disease using male huC2-KI mice were then used to assess the in vivo efficacy of CSL305. The first was an attenuated passive anti-glomerular basement membrane (GBM) glomerulonephritis model involving complement activation as its primary mechanism of action. CSL305 showed dose-dependent inhibition of disease as measured by urine albumin, with reductions in kidney cellular infiltration and plasma C3 cleaved fragments C3b/C3c/iC3b also observed. The second model was a collagen autoantibody-induced arthritis (CAIA) mouse model. Here, CSL305 showed a significant and dose-dependent inhibition of clinical score in both prophylactic and therapeutic settings, mediated exclusively via its FcRn mechanism of action. Although the animal models used in this study were found to preclude the demonstration of a synergistic effect on both mechanisms, CSL305 does act in vivo as both a complement inhibitor and as a FcRn antagonist to ameliorate disease.
2026-06-17 | When Atypical Becomes Typical: A Fulminant Seronegative Anti-GBM Disease.
Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disorder characterized by circulating anti-GBM antibodies, rapidly progressive glomerulonephritis, and linear immunoglobulin G (IgG) deposition along the GBM. In contrast, atypical anti-GBM disease presents with an indolent course, absence of detectable antibodies, and variable histologic features. We report a 24-year-old male who presented with severe kidney failure (serum creatinine 17 mg/dL) and no pulmonary symptoms. Serologic tests for anti-GBM, ANCA, and ANA were negative, and complement levels were normal. Kidney biopsy revealed crescentic glomerulonephritis with 55% cellular crescents and linear polytypic IgG and C3 staining along the GBM. The patient was treated with hemodialysis, high-dose corticosteroids, cyclophosphamide, and plasma exchange according to standard anti-GBM protocols. Antibody titers remained undetectable throughout therapy. Despite aggressive treatment, kidney function did not recover, leaving the patient dialysis-dependent. This case represents an atypical manifestation of atypical anti-GBM disease, mimicking the severe phenotype of the classic form but lacking serologic confirmation. It highlights the diagnostic uncertainty and therapeutic challenges in seronegative presentations, in which antibody titers cannot guide treatment or transplantation decisions. Such cases may be more accurately described as crescentic glomerulonephritis with linear IgG staining, reflecting their overlap with classic anti-GBM disease.
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.
2026-06-29 | Mechanistic Insights and Therapeutic Advances of Anti-Inflammatory Biologics in Immune-Mediated Glomerulonephritis: A Narrative Review.
Immune-mediated glomerulonephritis represents a diverse group of kidney disorders caused by dysregulated immune responses and constitutes a major contributor to chronic kidney disease. Its pathogenesis can be conceptualized as a three-step cascade: aberrant activation of innate immunity through pattern-recognition receptors, inflammasome complexes, and complement pathways; adaptive immune dysregulation characterized by imbalanced B- and T-cell responses and the production of pathogenic autoantibodies; and terminal effector injury involving complement-mediated damage and progressive fibrosis. This narrative review summarizes current advances in anti-inflammatory biologics that intervene at these critical points across a broad spectrum of entities, including IgA nephropathy (IgAN), membranous nephropathy (MN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), minimal change nephropathy (MCN), anti-glomerular basement membrane (anti-GBM) disease, ANCA-associated vasculitis (AAV), and C3 glomerulopathy (C3G). Therapies including cytokine inhibitors targeting TNF-α or IL-6, B-cell-depleting antibodies such as anti-CD20, plasma cell-directed agents, and complement blockers against C5 or Factor B have demonstrated clinical benefits in IgAN, MN, and LN, where evidence from randomized controlled trials supports their efficacy in reducing proteinuria and preserving renal function. For other entities such as FSGS, MCN, anti-GBM disease, and C3G, the evidence remains preliminary, based largely on case reports, preclinical models, or early-phase trials. Despite therapeutic advances, challenges persist regarding efficacy variability, infection risks, and financial burden. Future research aims to achieve precision therapy through multi-omics-based stratification, next-generation biologics such as bispecific antibodies and gene therapies, and optimized drug delivery systems, steering immune-mediated glomerulonephritis management toward truly disease-modifying treatment.
2026-06-26 | In Vivo Efficacy of an Inhibitor of Complement and FcRn in Models of Glomerulonephritis and Collagen-Induced Arthritis Using Human C2 Knock-In Mice.
A therapeutic antibody, CSL305, has been developed, which combines inhibition of the complement classical and lectin pathways via complement C2 binding with an ability to act as an antagonist of the neonatal Fc receptor (FcRn). CSL305 binds to human C2 (huC2) but shows no binding or activity against mouse C2 precluding its use in mouse models of disease to fully assess in vivo efficacy. To circumvent this, a mouse strain was developed that replaced the expression of mouse C2 with huC2 by homologous recombination. These mice (huC2 "knock-in"; KI) were shown to express huC2 protein and to have complement activity. Interestingly, male huC2-KI mice showed much stronger complement activity compared to female mice and were also sensitive to inhibition by CSL305. Two models of disease using male huC2-KI mice were then used to assess the in vivo efficacy of CSL305. The first was an attenuated passive anti-glomerular basement membrane (GBM) glomerulonephritis model involving complement activation as its primary mechanism of action. CSL305 showed dose-dependent inhibition of disease as measured by urine albumin, with reductions in kidney cellular infiltration and plasma C3 cleaved fragments C3b/C3c/iC3b also observed. The second model was a collagen autoantibody-induced arthritis (CAIA) mouse model. Here, CSL305 showed a significant and dose-dependent inhibition of clinical score in both prophylactic and therapeutic settings, mediated exclusively via its FcRn mechanism of action. Although the animal models used in this study were found to preclude the demonstration of a synergistic effect on both mechanisms, CSL305 does act in vivo as both a complement inhibitor and as a FcRn antagonist to ameliorate disease.
2026-06-17 | When Atypical Becomes Typical: A Fulminant Seronegative Anti-GBM Disease.
Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disorder characterized by circulating anti-GBM antibodies, rapidly progressive glomerulonephritis, and linear immunoglobulin G (IgG) deposition along the GBM. In contrast, atypical anti-GBM disease presents with an indolent course, absence of detectable antibodies, and variable histologic features. We report a 24-year-old male who presented with severe kidney failure (serum creatinine 17 mg/dL) and no pulmonary symptoms. Serologic tests for anti-GBM, ANCA, and ANA were negative, and complement levels were normal. Kidney biopsy revealed crescentic glomerulonephritis with 55% cellular crescents and linear polytypic IgG and C3 staining along the GBM. The patient was treated with hemodialysis, high-dose corticosteroids, cyclophosphamide, and plasma exchange according to standard anti-GBM protocols. Antibody titers remained undetectable throughout therapy. Despite aggressive treatment, kidney function did not recover, leaving the patient dialysis-dependent. This case represents an atypical manifestation of atypical anti-GBM disease, mimicking the severe phenotype of the classic form but lacking serologic confirmation. It highlights the diagnostic uncertainty and therapeutic challenges in seronegative presentations, in which antibody titers cannot guide treatment or transplantation decisions. Such cases may be more accurately described as crescentic glomerulonephritis with linear IgG staining, reflecting their overlap with classic anti-GBM disease.
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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 | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
veverimer | other | FDA | 2025-03-27 | — | Renibus Therapeutics Inc. |
Imlifidase | proteins | EMA | 2018-11-19 | — | Hansa Biopharma AB |
Imlifidase | proteins | FDA | 2018-07-03 | — | Hansa Medical AB |
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