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
688 drug discovery papers related to Anti-glomerular basement membrane disease, with 5 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
688 drug discovery papers related to Anti-glomerular basement membrane disease, with 5 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
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.
2026-06-30 | YS-1301 ameliorates crescentic glomerulonephritis by promoting immunoregulatory macrophages.
Anti-glomerular basement membrane (GBM) glomerulonephritis (GN) is a severe crescentic GN causing rapid renal failure. Despite extensive study of leukocyte-mediated injury, effective therapies that suppress inflammation and promote immunoregulation remain limited. YS-1301, a non-prostanoid prostacyclin receptor agonist and thromboxane synthase inhibitor, enhances tissue-protective factor release and modulates immune responses in other disease models. This study investigated whether YS-1301 ameliorates anti-GBM GN via immunomodulatory mechanisms. Crescentic GN was induced in WKY rats by intravenous injection of anti-GBM antibody clone TF78. YS-1301 (10 mg/kg/day) was administered intravenously after disease induction on days 0-2. Renal function and histologic injury were assessed on day 3, and additional cohorts were evaluated on day 7, the latest time point within the rapidly progressive GN phase of this model. Leukocyte infiltration and monocyte/macrophage phenotypes were evaluated by immunohistochemistry and flow cytometry. YS-1301 significantly reduced day-3 and day-7 blood urea nitrogen (BUN), serum creatinine, proteinuria, and crescent formation without altering initial glomerular antibody deposition. Total glomerular CD68+ cell numbers were unchanged, whereas glomerular CD163+ and CD206+ cell numbers increased. Flow cytometry confirmed that YS-1301 promoted enrichment of immunoregulatory/pro-resolving monocyte/macrophage populations, thereby shifting leukocytes toward an immunoregulatory state. When administered as an early post-induction intervention, YS-1301 ameliorated anti-GBM GN and was associated with localized accumulation of glomerular immunoregulatory macrophages rather than reduced total macrophage infiltration. These data support further evaluation of YS-1301 as an early immunomodulatory strategy for rapidly progressive GN.
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.
2026-07-07 | 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.
2026-06-30 | YS-1301 ameliorates crescentic glomerulonephritis by promoting immunoregulatory macrophages.
Anti-glomerular basement membrane (GBM) glomerulonephritis (GN) is a severe crescentic GN causing rapid renal failure. Despite extensive study of leukocyte-mediated injury, effective therapies that suppress inflammation and promote immunoregulation remain limited. YS-1301, a non-prostanoid prostacyclin receptor agonist and thromboxane synthase inhibitor, enhances tissue-protective factor release and modulates immune responses in other disease models. This study investigated whether YS-1301 ameliorates anti-GBM GN via immunomodulatory mechanisms. Crescentic GN was induced in WKY rats by intravenous injection of anti-GBM antibody clone TF78. YS-1301 (10 mg/kg/day) was administered intravenously after disease induction on days 0-2. Renal function and histologic injury were assessed on day 3, and additional cohorts were evaluated on day 7, the latest time point within the rapidly progressive GN phase of this model. Leukocyte infiltration and monocyte/macrophage phenotypes were evaluated by immunohistochemistry and flow cytometry. YS-1301 significantly reduced day-3 and day-7 blood urea nitrogen (BUN), serum creatinine, proteinuria, and crescent formation without altering initial glomerular antibody deposition. Total glomerular CD68+ cell numbers were unchanged, whereas glomerular CD163+ and CD206+ cell numbers increased. Flow cytometry confirmed that YS-1301 promoted enrichment of immunoregulatory/pro-resolving monocyte/macrophage populations, thereby shifting leukocytes toward an immunoregulatory state. When administered as an early post-induction intervention, YS-1301 ameliorated anti-GBM GN and was associated with localized accumulation of glomerular immunoregulatory macrophages rather than reduced total macrophage infiltration. These data support further evaluation of YS-1301 as an early immunomodulatory strategy for rapidly progressive GN.
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.
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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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