Anti-Glomerular Basement Membrane Disease

1. Disease Information

Overview. Anti-glomerular basement membrane (anti-GBM) disease is a rare, organ-specific autoimmune small-vessel vasculitis caused by circulating autoantibodies (predominantly IgG) directed against the non-collagenous-1 (NC1) domain of the α3 chain of type IV collagen — the "Goodpasture antigen" — which is expressed in the specialized basement membranes of the renal glomerulus and pulmonary alveolus. The classic presentation is a pulmonary–renal syndrome: rapidly progressive (crescentic) glomerulonephritis (RPGN) together with diffuse alveolar hemorrhage (DAH). When both organs are involved the term Goodpasture syndrome/disease is traditionally used; isolated renal-limited or (rarely) lung-limited forms also occur.

Key identifiers. - MONDO: MONDO:0009303 (anti-glomerular basement membrane disease) - OMIM: 233450 (GOODPASTURE SYNDROME) ✔ - Orphanet: ORPHA:375 (Anti-glomerular basement membrane disease / Goodpasture syndrome) - ICD-10: M31.0 (Hypersensitivity angiitis – Goodpasture syndrome); ICD-11: 4A44.A0 / GB61 cross-mapped - MeSH: D019867 "Anti-Glomerular Basement Membrane Disease" - UMLS/SNOMED CT: 236519009 (Anti-glomerular basement membrane disease)

Synonyms / alternative names. Goodpasture syndrome; Goodpasture disease; anti-GBM antibody disease; anti-basement-membrane antibody disease; pulmonary–renal syndrome (descriptive, not specific). The eponym honors Ernest Goodpasture, who described a fatal case during the 1919 influenza pandemic.

Data derivation. This entry is built from aggregated disease-level resources (systematic reviews/meta-analyses, single-center cohort series, mechanistic biochemistry) rather than individual EHR patients — appropriate given the disease's rarity.

2. Etiology

Causal mechanism

Anti-GBM disease is fundamentally an autoantibody-mediated (Type II hypersensitivity) conformeropathy. The proximate cause is the breakdown of immune tolerance to the α3(IV)NC1 domain, generating high-affinity IgG that binds basement-membrane antigen and triggers complement- and neutrophil-mediated necrotizing injury. It is not a Mendelian disease; it arises from a strong genetic susceptibility background acted on by an environmental "second hit."

Genetic risk factors

• HLA-DRB1*15:01 (DR15 haplotype) is the dominant susceptibility allele. It is "found in more than 80% of patients with anti-GBM antibody disease" (Medscape/Phelps & Rees ⚠ PMID:10231356). DRB1*15:01 and DRB1*04 are positively associated.
• Susceptibility loci: Phelps & Rees (Kidney Int 1999 ⚠ PMID:10231356) established the HLA-DRB1 dominance hierarchy of risk.

Genetic protective factors

• HLA-DRB1*07:01 (and DRB1*01) confer dominant protection: "individuals inheriting DRB1*1501 and DRB1*0701 have no higher risk of disease than does the general population" (Medscape synthesis of Phelps & Rees ⚠).

Environmental / acquired risk factors ("second hits" that expose the cryptic antigen)

• Cigarette smoking — strongly associated, especially with the pulmonary-hemorrhage phenotype.
• Hydrocarbon / organic-solvent inhalation — classic occupational/inhalational trigger (case literature, e.g., Egyptian J Bronchol 2026).
• Pulmonary infection (viral respiratory infections, influenza historically).
• Extracorporeal shock-wave lithotripsy — "can disrupt the glomerular basement membrane and unmask epitopes" (Merck Manual / CJASN review).
• Alemtuzumab (anti-CD52) — lymphocyte-depleting therapy; "loss of regulatory T cell subsets, or abnormal immune cell repopulation after depletion" (PMC7573726 ⚠).
• Membranous nephropathy and ANCA-associated vasculitis can precede or co-occur, "unmasking" GBM antigen.
• Age/sex: bimodal age peaks (young men 20–30; older adults 60–70, more women).

Gene–environment interaction. The canonical model: an HLA-DRB1*15:01–restricted CD4⁺ T-cell response to α3(IV)NC1 epitopes provides help for autoantibody production, but disease only manifests when an environmental insult (smoke, hydrocarbons, infection, lithotripsy) perturbs the GBM and exposes the normally sequestered cryptic epitopes — converting subclinical autoreactivity into overt injury.

3. Phenotypes

Characteristics. Onset is typically acute/subacute in adults; the disease is monophasic in classic single-positive cases (relapse <3%). Severity is severe and often organ-threatening at presentation. Pulmonary hemorrhage can be immediately life-threatening; renal disease frequently progresses to end-stage within days–weeks if untreated.

Quality-of-life impact. Survivors who reach ESRD face lifelong dialysis or transplantation; pulmonary survivors generally recover lung function. No disease-specific QoL instrument exists; generic CKD/dialysis QoL measures (KDQOL, EQ-5D, SF-36) apply.

4. Genetic / Molecular Information

This is NOT a monogenic disease — there are no causal germline mutations. The "molecular genetics" is the genetics of the autoantigen and of HLA susceptibility.

• Autoantigen gene: COL4A3 (HGNC:2204; chromosome 2q36.3), encoding the α3 chain of type IV collagen. Its C-terminal NC1 domain (α3(IV)NC1) is the Goodpasture antigen. The collateral chains COL4A4 (HGNC:2205) and COL4A5 (HGNC:2207, Xq22.3) form the α3α4α5(IV) network.
• Susceptibility "gene": HLA class II — HLA-DRB1 (HGNC:4948), allele DRB1*15:01.
• No pathogenic somatic variants, copy-number, or chromosomal abnormalities are implicated in pathogenesis. (Conversely, loss-of-function mutations in COL4A3/4/5 cause Alport syndrome — and transplanted Alport patients can develop de novo anti-GBM antibodies against the newly encountered α3/α5(IV) antigen, the converse experiment of nature.)
• Functional consequence: The disease results from a conformational change, not a sequence change — see Mechanism.

Epigenetics / molecular profiling. No established disease-specific methylation/histone signature. Transcriptomic/proteomic profiling is largely confined to research cohorts; no validated multi-omics diagnostic exists.

5. Environmental Information

• Toxins / inhalational: organic solvents and hydrocarbons (gasoline, paint thinners); cigarette smoke is the best-established lifestyle exposure and disproportionately drives the alveolar-hemorrhage phenotype.
• Mechanical: extracorporeal shock-wave lithotripsy (GBM disruption).
• Iatrogenic: alemtuzumab and other lymphocyte-depleting agents.
• Infectious agents: respiratory viral infections (historically influenza — Goodpasture's index 1919 case); no single pathogen is causal. Infection is regarded as a nonspecific trigger/adjuvant rather than an etiologic organism.

6. Mechanism / Pathophysiology

This is the mechanistic core and the best-characterized aspect of the disease — a model "autoimmune conformeropathy."

Step 1 — The sequestered/cryptic autoantigen and its "immune privilege"

The Goodpasture antigen is the C-terminal NC1 domain of α3(IV) collagen, identified by Saus, Hudson and colleagues as the common target of anti-basement-membrane antibodies (✔ PMID:8589284):

"Reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease directed to the NC1 domain of Type IV collagen."

In the mature GBM, six NC1 domains associate into an α3α4α5 NC1 hexamer (two trimeric "caps" joined head-to-head). The two immunodominant epitopes — E_A and E_B, located on α3(IV)NC1 — are buried by intraprotomer interactions with α4 and α5 NC1 domains and locked by novel sulfilimine (S=N) crosslinks discovered by Vanacore et al. (Science 2009 ⚠ PMID:19729652). These crosslinks "confer immune privilege to the Goodpasture autoantigen" by structurally sequestering the cryptic epitopes.

Step 2 — Conformational unmasking (the "conformeropathy")

Pedchenko et al. (NEJM 2010 ⚠ PMID:20660402, Molecular Architecture of the Goodpasture Autoantigen in Anti-GBM Nephritis) showed that:

"the autoantibodies bind neoepitopes formed on α3 and α5 NC1 subunits upon disruption of the quaternary structure of the native α345NC1 hexamer, and hexamer disruption is concomitant with conformational changes that transition subunits into immunogens."

An environmental insult (oxidants from smoke, infection, mechanical disruption) dissociates the hexamer, exposing E_A/E_B. Autoantibodies to the α5(IV)NC1 chain are also pathogenic, defining a broader α3/α5 conformeropathy (Pedchenko 2016 ⚠, PMC5600521).

Step 3 — Loss of tolerance and antibody production

An HLA-DRB1*15:01–restricted CD4⁺ T-cell response to α3(IV)NC1 peptides drives B-cell help; B cells (CL:0000236) differentiate into plasma cells producing high-affinity, complement-fixing IgG1/IgG3 anti-GBM antibodies. The autoantibody titer correlates with disease activity.

Step 4 — Antibody binding, complement activation, effector recruitment

Circulating IgG binds the exposed α3(IV)NC1 along the GBM in a linear, ribbon-like immunofluorescence pattern. This activates the classical complement pathway (C3, C5a), generating chemoattractants that recruit neutrophils (CL:0000775) and monocytes/macrophages (CL:0000235). Effector cells release proteases and reactive oxygen species, producing fibrinoid necrosis of capillary loops.

Step 5 — Crescent formation and tissue destruction

GBM rupture permits fibrin and inflammatory cells into Bowman's space, triggering parietal epithelial and podocyte proliferation → cellular crescents → crescentic (extracapillary) glomerulonephritis. In the lung, alveolar capillary basement-membrane injury causes diffuse alveolar hemorrhage. Smoking increases alveolar antigen accessibility, explaining the smoking–lung-hemorrhage link.

Causal chain (upstream → downstream)

HLA-DRB1*15:01 susceptibility + environmental insult → hexamer dissociation/oxidation → exposure of cryptic E_A/E_B on α3/α5(IV)NC1 → T-cell-dependent anti-GBM IgG production → linear GBM antibody deposition → classical complement activation + neutrophil recruitment → capillary fibrinoid necrosis → crescentic GN (kidney) and alveolar hemorrhage (lung) → RPGN/ESRD and respiratory failure.

Ontology suggestions

• Biological processes (GO): GO:0006956 complement activation; GO:0006958 complement activation, classical pathway; GO:0002455 humoral immune response mediated by circulating immunoglobulin; GO:0050900 leukocyte migration; GO:0006954 inflammatory response; GO:0002544 chronic inflammation; GO:0030198 extracellular matrix organization.
• Cell types (CL): CL:0000236 B cell; CL:0000775 neutrophil; CL:0000235 macrophage; CL:0000084 T cell; CL:1000746 glomerular visceral epithelial cell (podocyte); CL:1000698 kidney resident parietal epithelial cell (crescent precursor).
• Pathways: Reactome R-HSA-2559639 (Collagen type IV sulfilimine cross-linking by peroxidasin); Reactome complement cascade R-HSA-166658.
• Protein dysfunction: No protein misfolding mutation — pathology is a quaternary conformational change exposing cryptic epitopes (a structural neoepitope phenomenon).

7. Anatomical Structures Affected

• Primary organs: Kidney (UBERON:0002113) — specifically the renal glomerulus (UBERON:0000074) and glomerular basement membrane (UBERON:0002164); Lung (UBERON:0002048) — pulmonary alveolus (UBERON:0002299) and alveolar basement membrane.
• Body systems: renal/urinary and respiratory; secondarily hematologic (hemorrhagic anemia).
• Tissue/cell level: glomerular capillary endothelium and podocytes; alveolar capillary endothelium/type I pneumocytes; the target is the specialized type IV collagen network of these basement membranes (α3α4α5, restricted to GBM, alveolus, cochlea, eye, testis — explaining organ selectivity).
• Subcellular (GO Cellular Component): GO:0005604 basement membrane; GO:0005581 collagen trimer; GO:0005615 extracellular space.
• Lateralization: bilateral (both kidneys, both lungs) — diffuse, antigen-driven.

8. Temporal Development

• Onset: acute/subacute in adults; bimodal age distribution — a peak in young men (20–30 yr, often with pulmonary–renal disease) and a second in older adults (60–70 yr, more women, often renal-limited).
• Progression: characteristically rapidly progressive — kidney function can decline from normal to dialysis-dependence over days. Untreated, prognosis is dismal.
• Course pattern: classic single-positive disease is monophasic (one episode, no relapse if antibody is cleared). Relapse is <3% (NDT treatment-standard review ✔). Double-positive (anti-GBM + ANCA) patients behave more like ANCA-associated vasculitis with relapsing-remitting disease (~50% relapse).
• Critical window: the therapeutic window is extremely narrow — outcomes hinge on starting plasma exchange/immunosuppression before oliguria/dialysis dependence is established. Patients dialysis-dependent >7 days before treatment "very rarely recover independent kidney function."

9. Inheritance and Population

Epidemiology (✔ systematic review/meta-analysis, PMID:38493958 — 47 studies, 2,830 patients)

• Incidence: "The overall incidence of anti-GBM disease ranged from 0.60 to 1.79 per million population per annum." (≈0.5–1 case/million/year is the commonly quoted figure.)
• Anti-GBM accounts for ~8.0% of rapidly progressive GN and ~12.8% of crescentic GN cases (pooled).
• Anti-GBM antibody positivity: 88.8%; ANCA co-positivity (double-positive): 27.4%; pulmonary hemorrhage: 32.6%.

Inheritance

• Not Mendelian — complex/multifactorial with strong HLA association. No vertical inheritance pattern, no penetrance/expressivity/anticipation/mosaicism/founder-effect parameters apply in the classic genetic sense.
• Rare familial clustering in HLA-identical siblings is reported (Clin Kidney J 2020), consistent with shared HLA-DR15 susceptibility rather than a transmitted causal variant.

Demographics

• Sex: historically male predominance (~3:2) overall, but the older renal-limited peak skews female.
• Ethnicity: "reported in all racial groups but is primarily a disease of white populations," with ~83% of race-identified cases in white individuals; relatively more common in those of European and East Asian descent. HLA-DRB1*15:01 frequency shapes geographic risk.
• Geographic clustering / seasonality: small temporal/geographic clusters reported (e.g., post-infection clusters; a noted rise during the COVID-19 pandemic period in Madrid, PMC12457157 ⚠).

10. Diagnostics

Serology (cornerstone)

• Circulating anti-GBM antibodies by ELISA (anti-α3(IV)NC1) — high sensitivity/specificity; titer tracks activity. LOINC examples: LOINC:40663-6 (Glomerular basement membrane Ab [Units/vol] in Serum by Immunoassay).
• ANCA panel (MPO/PR3) — must be tested in every patient: ~27–40% are double-positive, which changes prognosis and maintenance therapy.

Histopathology (definitive)

• Renal biopsy: diffuse crescentic glomerulonephritis on light microscopy; the pathognomonic finding is linear (ribbon-like) IgG deposition along the GBM on direct immunofluorescence (often with linear C3). Quantifying % crescents and % globally sclerosed glomeruli is essential for prognosis.
• Lung: capillaritis with hemorrhage; hemosiderin-laden macrophages on BAL.

Supporting laboratory / functional

• Urinalysis: dysmorphic hematuria, RBC casts, sub-nephrotic proteinuria; rising creatinine/falling GFR.
• Anemia (hemorrhagic/iron-deficiency).
• Imaging: chest CT/X-ray showing bilateral alveolar infiltrates (RadLex); DLCO is paradoxically increased during active alveolar hemorrhage (a useful functional clue).
• Genetic testing: not diagnostic (no causal gene). HLA typing is research/risk-stratification only.

Differential diagnosis

ANCA-associated vasculitis (GPA/MPA), lupus nephritis, other causes of pulmonary–renal syndrome, IgA/IgA-vasculitis nephritis, thrombotic microangiopathy, and (importantly) double-positive anti-GBM/ANCA disease. Distinguishing feature: linear (anti-GBM) vs pauci-immune (ANCA) vs granular (immune-complex) IF staining.

11. Outcome / Prognosis

Survival (✔ meta-analysis PMID:38493958)

• 1-year patient survival: 76.2%; 1-year kidney survival: 30.2%.

Landmark prognostic cohort (Levy et al., Ann Intern Med 2001 ⚠ PMID:11712875; n=71, plasma exchange + prednisolone + cyclophosphamide)

• Patients presenting with creatinine <500 µmol/L (<5.7 mg/dL): ~100% patient and 95% renal survival at 1 year (84%/74% longer-term).
• Patients presenting dialysis-dependent / creatinine very high / ~100% crescents: dismal renal recovery.

Strongest prognostic factors

1. Baseline serum creatinine / dialysis dependence at presentation (the single most powerful predictor).
2. Oliguria.
3. Percentage of glomeruli with crescents and normal-glomeruli percentage (✔ meta-analysis: "Kidney function on diagnosis and normal glomeruli percentage were identified as strong prognostic factors").
4. Time from symptom onset to treatment.

For dialysis-dependent patients, only ~8% recovered independent kidney function at 1 year (recent series ~17–20%); recovery is essentially confined to those with <100% crescents, <50% glomerulosclerosis, non-oliguric, and dialysis started <72 h (NDT review ✔).

Disease course / complications

• Pulmonary hemorrhage: high remission with treatment (90–100%) but acutely life-threatening.
• Complications: ESRD requiring dialysis/transplant; treatment-related infection (immunosuppression), hemorrhage.
• Relapse: <3% in classic single-positive disease; high in double-positive disease.

12. Treatment

The triad of plasma exchange + corticosteroids + cyclophosphamide remains standard of care; it transformed a near-uniformly fatal disease into a treatable one. Specifics below are from the 2026 NDT treatment-standard review (✔).

Standard induction

• Plasma exchange (PLEX) — MAXO:0000548 (therapeutic plasmapheresis) / NCIT:C15304 (Plasmapheresis): "Daily 40–60 mL/kg exchange for 5% human albumin solution" until antibody fully suppressed, "typically 14 days." Removes circulating pathogenic IgG. (Use fresh frozen plasma replacement if pulmonary hemorrhage/recent biopsy.)
• Glucocorticoids — MAXO:0000058 / NCIT:C15986 (Pharmacotherapy), agent corticosteroid: "Prednisolone 1 mg/kg/day (maximum 60 mg) orally," tapered to 20 mg by 6 weeks then off by 6 months. Suppresses inflammation.
• Cyclophosphamide — MAXO:0000647 (chemotherapy/cytotoxic), agent cyclophosphamide CHEBI:4027: "2–3 mg/kg/day (ideal body weight; maximum 200 mg) orally for 2–3 months," dose-reduced in age >55 or dialysis dependence. Suppresses new autoantibody production.

Emerging / alternative agents

• Rituximab (anti-CD20, B-cell depletion; NCIT:C1702): "2× 1 g at day 0 and 14 OR 375 mg/m² weekly ×4"; used when cyclophosphamide is contraindicated or in refractory disease. A 2025 review of 67 patients reported 91% patient survival, 67% kidney survival (✔). Evidence base remains limited.
• Imlifidase (IdeS, IgG-degrading enzyme of S. pyogenes; NCIT term for imlifidase): "Cleaves all circulating (and potentially tissue bound) IgG at the hinge region" with onset in 2–6 h. Phase 2: 67% dialysis-independent at 6 months vs 18% historic controls; pivotal Phase 3 GOOD-IDES-02 (NCT05679401) completed recruitment, results anticipated late 2025. Dose 0.25–0.5 mg/kg single dose. Potential paradigm shift for rapid antibody clearance.

Treatment-decision rules

• Treat pulmonary hemorrhage aggressively regardless of renal status: "Treatment is always recommended when alveolar haemorrhage is present, regardless of the presence or severity of kidney disease."
• Dialysis-dependent with 100% crescents and no lung hemorrhage: intensive immunosuppression often withheld (futile renal recovery, high infection risk) — individualized.

Supportive / prophylactic care

Pneumocystis jirovecii prophylaxis, antifungal and peptic-ulcer prophylaxis, osteoporosis prevention during high-dose steroids/cyclophosphamide. MAXO:0000950 (supportive care).

Maintenance & transplantation

• Classic single-positive disease: maintenance immunosuppression not routinely required (monophasic).
• Double-positive disease: treat maintenance as for ANCA-associated vasculitis.
• Kidney transplantation (MAXO:0010039 organ transplantation): delay until ≥6 months of sustained anti-GBM seronegativity; transplanting with circulating antibody risks recurrence "up to 50%," but with seronegativity recurrence is rare.

Pharmacogenomics

No validated PGx markers specific to anti-GBM; standard cyclophosphamide considerations (gonadal toxicity, fertility preservation counseling) apply.

13. Prevention

• Primary prevention: no vaccine/screening (rare, sporadic). Risk-factor modification is the main lever — smoking cessation and avoiding hydrocarbon/solvent exposure, especially in HLA-DR15 carriers (e.g., after lithotripsy or in Alport transplant recipients).
• Secondary prevention: early recognition of pulmonary–renal syndrome and urgent anti-GBM/ANCA serology + biopsy — the closest analog to "early detection," because outcome is time-critical.
• Tertiary prevention: monitor antibody titers to confirm clearance before transplantation; treat double-positive patients with maintenance therapy to prevent relapse; infection prophylaxis during immunosuppression.
• Genetic counseling: limited utility — HLA association is a risk factor, not a deterministic inherited mutation; familial recurrence is rare.

14. Other Species / Natural Disease

• Taxonomy: primarily a human disease (NCBITaxon:9606).
• Natural animal disease: spontaneous anti-GBM/Goodpasture-like disease is uncommon in domestic animals; isolated case reports exist in dogs and horses. The α3α4α5(IV) collagen network is evolutionarily conserved across mammals, so the antigen exists in all species.
• Comparative biology: the conserved type IV collagen network and sulfilimine crosslinks (found broadly across Metazoa) underlie why rodent immunization models faithfully reproduce human disease. Orthologs: mouse Col4a3, Col4a4, Col4a5.
• Zoonosis: none — autoimmune, not transmissible.

15. Model Organisms

• Experimental autoimmune glomerulonephritis (EAG): the principal model — rats (WKY strain) and mice immunized with α3(IV)NC1 or GBM preparations develop crescentic GN and linear IgG deposition, recapitulating human kidney pathology. Used to define T-cell epitopes and HLA-restricted responses.
• Nephrotoxic nephritis (NTN / "anti-GBM nephritis"): heterologous anti-GBM antiserum injected into rodents — a workhorse model of crescentic GN effector mechanisms (complement, neutrophils, macrophages). Caveat: models antibody effector injury, not the spontaneous loss of tolerance.
• HLA-transgenic mice (DR15 / DR4 / DR1): demonstrate HLA-restricted susceptibility/protection, directly modeling the human HLA association.
• Col4a3-knockout mouse (Alport model): lacks the antigen; used to study de novo anti-GBM/alloimmunity after antigen re-exposure (analogous to post-transplant Alport anti-GBM).
• Model characteristics: EAG reproduces linear IF, crescents, and pulmonary involvement (variably); limitations — rodent disease is often less fulminant in the lung, and tolerance-breaking is artificially induced rather than spontaneous.
• Resources: MGI for Col4a3/4/5; rat models via RGD; immunization protocols in primary EAG literature.

Key References (verify PMIDs before KB ingestion)

1. ✔ Hellmark/Saus/Hudson et al. Identification of the α3 chain of type IV collagen as the common autoantigen in anti-basement-membrane disease and Goodpasture syndrome. PMID:8589284. — "Reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary…"
2. ⚠ Pedchenko V, et al. Molecular Architecture of the Goodpasture Autoantigen in Anti-GBM Nephritis. N Engl J Med 2010;363:343–354. PMID:20660402. — conformeropathy / neoepitope mechanism.
3. ⚠ Vanacore R, et al. A sulfilimine bond identified in collagen IV. Science 2009;325:1230–1234. PMID:19729652. — immune-privilege crosslink (PMC2876822).
4. ✔ Systematic review & meta-analysis (47 studies, 2,830 patients). PMID:38493958. — incidence 0.60–1.79/million/yr; 1-yr patient survival 76.2%, kidney survival 30.2%; pulmonary hemorrhage 32.6%; ANCA 27.4%.
5. ⚠ Levy JB, et al. Long-term outcome of anti-GBM antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med 2001;134:1033. PMID:11712875. — creatinine-stratified prognosis.
6. ✔ Levy JB, et al. Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. Kidney Int 2004. PMID:15458448.
7. ✔ McAdoo SP, et al. Patients double-seropositive for ANCA and anti-GBM antibodies… Kidney Int 2017. PMID:28506760.
8. ⚠ McAdoo SP, Pusey CD. Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol 2017;12:1162. PMID:28515156 (review).
9. ⚠ Phelps RG, Rees AJ. The HLA complex in Goodpasture's disease. Kidney Int 1999. PMID:10231356 — DRB1*15:01 risk, DRB1*07:01 protection.
10. ⚠ Anti-GBM disease — treatment standard. Nephrol Dial Transplant 2026;41:42. — regimen, rituximab, imlifidase/GOOD-IDES-02 (NCT05679401).

Sources (URLs): - PubMed 8589284 — α3(IV) autoantigen - NEJM — Molecular Architecture of the Goodpasture Autoantigen (Pedchenko 2010) - Antibodies to α5(IV) are pathogenic — PMC5600521 - PubMed 38493958 — Epidemiology/outcomes systematic review & meta-analysis - Levy 2001 — Ann Intern Med long-term outcome - PubMed 15458448 — ANCA + anti-GBM double-positive (Levy 2004) - PubMed 28506760 — double-seropositive renal survival/relapse (McAdoo 2017) - CJASN 2017 — McAdoo & Pusey review - NDT 2026 — Anti-GBM disease treatment standard - HLA-DRB1 susceptibility — ScienceDirect/Kidney Int - Medscape — Anti-GBM Antibody Disease (HLA, demographics) - Merck Manual — Anti-GBM Disease (triggers) - Vanacore 2009 Science — sulfilimine bond (PMC2876822) - Goodpasture conformeropathy review — PMC6482832 - Alemtuzumab-related anti-GBM — PMC7573726 - OMIM 233450 — Goodpasture syndrome

Summary for KB population

The existing kb/disorders/Anti-GBM_Disease.yaml already captures the correct backbone (MONDO:0009303, α3(IV)NC1 autoantigen, HLA-DRB1*15:01, the 3-node B-cell→complement/neutrophil→crescentic-GN/alveolar-hemorrhage pathophysiology chain, and plasma exchange treatment). This report supplies the evidence to flesh it out: add the conformeropathy/neoepitope mechanism node (PMID:20660402, 8589284) with the sulfilimine immune-privilege detail (PMID:19729652); add double-positive ANCA as a distinct trajectory; add quantitative phenotype frequencies (pulmonary hemorrhage 32.6%) and outcomes (1-yr survival 76.2%/30.2%) from PMID:38493958; add cyclophosphamide, corticosteroids, rituximab, and imlifidase treatments with MAXO/NCIT/CHEBI terms and the GOOD-IDES-02 trial (NCT05679401); and add smoking/hydrocarbon/lithotripsy/alemtuzumab environmental triggers. Re-fetch and substring-verify every ⚠ PMID with just fetch-reference before adding any evidence snippet.