Anti-GBM Disease
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Direct answer
Goodpasture's antigen sits on the alpha-3 chain of type IV collagen in the glomerular and alveolar basement membranes, and antibodies against it produce the most explosive of the pulmonary–renal syndromes: a young male smoker with haemoptysis and a creatinine doubling by the week, or an older woman with renal-limited crescentic disease. Immunofluorescence is the diagnostic theatre — smooth linear IgG along every glomerular capillary wall, with no complement-heavy granularity. Treatment is the oldest protocol still standing in nephrology: daily plasmapheresis to strip the antibody, cyclophosphamide to stop its production, and high-dose steroids to hold the injury until both take effect, ideally begun before the creatinine reaches dialysis range.
What you must remember
- Antigen: alpha-3 chain NC1 domain of type IV collagen — the exam's one-word answer.
- Bimodal age curve: young men, 20s to 30s, smokers, with pulmonary haemorrhage; older women, 60s, with kidney-only disease; smoking and pulmonary infection drive the lung bleed.
- Linear IgG: smooth ribbon along the glomerular basement membrane on direct immunofluorescence, with C3 characteristically normal — the single most-tested image in this territory.
- Dual positivity: a substantial minority — up to a third in some series — also carries ANCA (usually MPO); these double-positive patients relapse like vasculitis and need maintenance immunosuppression after the anti-GBM protocol ends.
- Protocol: daily or alternate-day plasma exchange with albumin (fresh frozen plasma if bleeding), oral cyclophosphamide and pulsed then oral steroids, continued about two weeks beyond the disappearance of circulating antibody.
- Futility threshold: dialysis-dependence at presentation with 100 per cent crescents and no pulmonary haemorrhage predicts non-recovery, and immunosuppression may reasonably be withheld — a decision the exam expects you to know exists.
- Transplant rule: wait until anti-GBM antibody is undetectable for six to twelve months; recurrence in the graft is then rare.
- Alport variant: de novo anti-GBM disease after transplantation in Alport syndrome affects roughly 3–5 per cent of transplanted males with truncating COL4A5 mutations — appears later, lacks pulmonary involvement, and usually loses the graft.
Haemoptysis with a creatinine of five
A 26-year-old man, twenty cigarettes a day since college, arrives coughing frank blood with a creatinine of 5.1 mg/dL that was 1.2 two weeks ago. Step one: stabilise and think in parallel — the pulmonary–renal differential is anti-GBM disease, ANCA vasculitis, lupus, antiphospholipid syndrome with catastrophes, cryoglobulinaemia and infective endocarditis, and the first two dominate. Step two: send anti-GBM serology and ANCA on the first draw, cross-match, and correct coagulopathy before any biopsy; a bleeding lung makes an uncorrected biopsy reckless. Step three: start empirically while waiting — in a patient this florid, plasmapheresis, cyclophosphamide and methylprednisolone begin on clinical suspicion, because the kidney loses a percentage of function each day the antibody circulates. Step four: the biopsy returns linear IgG with 85 per cent crescents — immunosuppression continues, since he still has pulmonary disease and non-oliguric renal function; had he been anuric with every glomerulus crescentic and clear lungs, the same biopsy would argue for restraint. Step five: after two weeks of daily exchange with falling titres, convert to recovery-phase management, and if the ANCA also returns positive, plan long-term vasculitis-style maintenance rather than a clean stop.
How the examiner frames it
Three framings recur. The image question shows the linear fluorescence and expects anti-GBM over granular lupus or the pauci-immune field. The double-positive stem gives you a patient who recovers, then relapses a year later — the teaching being that pure anti-GBM disease is monophasic, and relapse means the ANCA arm was missed. The transplant stem gives an Alport recipient, years after grafting, with a rapidly failing kidney and linear IgG — de novo anti-GBM disease, no lung involvement, poor salvage, distinct from classical Goodpasture's in every respect but the fluorescence pattern. One viva flourish is remembered: the eponym is strict — Goodpasture described the pulmonary–renal syndrome, the antigen carries the name, and the disease with kidney alone is still anti-GBM disease, not "Goodpasture's of the kidney".
Frequently asked questions
What is the target antigen in anti-GBM disease?
The NC1 domain of the alpha-3 chain of type IV collagen, shared by glomerular and alveolar basement membranes.
What is the standard treatment protocol?
Daily plasmapheresis with albumin replacement, cyclophosphamide and high-dose corticosteroids, continued until circulating antibody clears — roughly two weeks beyond.
When may immunosuppression reasonably be withheld?
Dialysis-dependence at presentation with every glomerulus crescentic and no pulmonary haemorrhage — recovery of independent renal function is rare enough to justify restraint.
How long after antibody clearance should transplantation wait?
Six to twelve months of undetectable anti-GBM antibody before listing; recurrence is then uncommon.
What distinguishes Alport post-transplant anti-GBM disease?
It is de novo, appears months to years after grafting, spares the lung, resists therapy and typically loses the graft.
What does dual ANCA positivity change?
It adds a relapsing vasculitis course, mandating maintenance immunosuppression after the acute anti-GBM protocol.