A ZENG1, K MARTIN1, S HOLT1,2, A BAJEL3, A MURUGASU2,4, T BARBOUR1,2
1Department of Nephrology, Royal Melbourne Hospital, Parkville, Australia, 2Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Australia, 3Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Parkville, Australia, 4Department of Medicine (RMH), University of Melbourne, Parkville, Australia
Background: In anti-glomerular basement membrane (anti-GBM) disease, autoantibodies against the non-collagenous domain of the alpha-3 chain of type IV collagen (α3[IV]NC1) cause rapidly progressive glomerulonephritis (GN). We present an atypical case in which focal and segmental glomerulosclerosis (FSGS) was associated with linear staining for IgG, yet without detection of circulating anti-α3[IV]NC1 antibodies.
Case Report: A 61-year-old woman developed nephrotic syndrome (uPCR 2196mg/mmol, serum albumin 13g/L, serum creatinine 74umol/L) 12 months after undergoing allogeneic bone marrow transplantation for acute myeloid leukaemia. Graft versus host disease (GVHD) prophylaxis with ciclosporin had been ceased early due to gastrointestinal upset. Past medical history included bipolar affective disorder, treated hepatitis B and C viral infections, Hashimoto’s thyroiditis and heavy cigarette smoking, with no other recreational drug use or hydrocarbon exposure. Autoimmune serologies including anti-GBM ELISA were negative. Renal biopsy showed 3/24 glomeruli globally sclerosed, 5 early focal segmental lesions, no proliferative change and only mild interstitial fibrosis and tubular atrophy. Strong immunoperoxidase staining for IgG alone was seen in a linear pattern. On electron microscopy, the GBM was of normal thickness, with >90% podocyte foot process effacement and no immune deposits.
After treatment with prednisolone 50mg daily for two months (weight 48kg), persisting heavy proteinuria prompted ciclosporin at an initial dose of 75mg twice daily, leading to complete remission.
Conclusions: Chronic GVHD involves B-cell dysregulation with a high prevalence of antibodies to cell surface and intracellular antigens. This case of atypical anti-GBM GN may represent chronic GVHD, with circulating antibodies towards a GBM antigen other than α3[IV]NC1.
Angela is a Basic Physician Trainee at the Royal Melbourne Hospital in Victoria. She has a keen interest in the areas of nephrology and geriatric medicine.