Introduction:
Anti-glomerular basement membrane (GBM) antibodies are highly specific for Goodpasture’s or anti-GBM disease, in which they are generally directed against the non-collagenous (NC1) domain of the alpha 3 chain of type IV collagen(α3(IV)), and less commonly, toward the α 4(IV) or α 5(IV) chains, which form a triple helical structure in GBM and alveolar basement membrane (ABM). Alterations in the hexameric structure of the NC1 (α3(IV)), allow novel epitopes to be exposed and an immune response to develop, with subsequent linear antibody deposition along the GBM, leading to a crescentic glomerulonephritis. Positive anti-GBM antibodies are assumed to be pathogenic and capable of binding GBM in vivo, especially in the context of rapidly progressive glomerulonephritis. Anti-GBM antibodies are considered diagnostic and it has been suggested that the level of anti-GBM antibodies correlates with long-term prognosis.
Here we present a patient with circulating anti-GBM antibodies at a significant titre with necrotising crescentic glomerulonephritis but no linear GBM antibody deposition on immunohistochemistry. Following treatment as per anti-GBM disease guidelines there was significant renal recovery
Methods:
It is an observational study of a case
Results:
A 24-year-old Asian female, a known thalassemic trait with no previous co-morbidities, with normal renal function and nil proteinuria 6 months back; was admitted to the hospital with symptoms of nausea and vomiting. Her blood pressure was in the normal range not requiring any anti-hypertensives. She gives a history of upper respiratory tract infection symptoms being treated with a short course of antibiotics 2-3 weeks prior. On admission, she was found to have a creatinine of 5.3 mg/dl which subsequently increased to 7.5 mg/dl requiring a few sessions of hemodialysis, and severe anaemia with hemoglobin of 6.9 g/dl dropping to 4.9 g/dl requiring multiple blood transfusions. On further evaluation, urine showed sub-nephrotic range proteinuria with active sediments. A diagnosis of RPRF-RPGN was made and she was pulsed with I.V Methyl prednisolone 1.5 gms over 3 days and underwent a renal biopsy. In the meantime, further workup showed ANA by IF- negative, MPO-ANCA, and PR3-ANCA- negative, complement C3- normal. Anti-GBM was positive with titers as high as 622 eliau/ml). Renal biopsy showed pauci immune necrotizing crescentric glomerulonephritis (DIF-negative). in view of RPRF-RPGN with anti-GBM disease, she received 7 sessions of plasmapheresis along with 2 doses of I.v cyclophosphamide. Following 7 sessions of plasmapheresis her anti-GBM titers decreased to 27 eliau/ml and she became dialysis independent with creatinine recovering to to 2.5 mg/dl. she was then treated with oral cyclophosphamide and oral steroid for a period of 3 months. Creatinine further recovered and reached a nadir of 2.0 mg/dl. Her anti-GBM titers at the end of 3 months of treatment reached to 4.3 eliau/ml.
Conclusions:
These novel findings, demonstrate that in some patients anti-GBM antibodies may not bind their own GBM.This has important implications for clinical diagnosis, suggesting that apart from histological confirmation of kidney injury by anti-GBM antibodies demonstrated by linear igG deposits in GBM through kidney biopsy, serological confirmation through anti GBM antibodies should also be obtained, as non-binding GBM antibodies levels may correlate with significant renal recovery.
I have no potential conflict of interest to disclose.
I used generative AI and AI-assisted technologies in the writing process.