An Interesting Case of Anti-Glomerular Basement Membrane Disease Mediated By IGA Autoantibodies
American Journal of Kidney Diseases
Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune condition in which circulating autoantibodies target the type IV collagen of the basement membranes found in the glomeruli and/or alveoli. Patients typically present with alveolar hemorrhage and rapidly progressive glomerulonephritis (RPGN) characterized histologically by crescents and linear deposition of IgG in the GBM. We describe a case of renal-limited anti-GBM disease with IgA deposition along the GBM and crescentic glomerular disease. The patient is a 75 year old male with a history of CKDIII who presented with dyspnea and leg edema over 1 month. His serum creatinine on admission was 3.24mg/dL, up from his baseline of ~1.8 two months ago. Urine chemistry revealed RBC>20, and nephrotic range proteinuria (16.02 g/d), . Immunologic studies were negative for anti-GBM IgG antibodies, ANA, ANCA and phospholipid receptor A2 IgG antibodies. Complement C3 and C4 levels were normal. Protein electrophoresis did not reveal monoclonal proteins. Ultrasound examination revealed ~13cm kidneys with normal corticomedullary differentiation. CT-chest was not consistent with alveolar hemorrhage. The renal biopsy revealed glomerulonephritis with cellular crescents in the background of moderate to severe interstitial fibrosis and tubular atrophy. A total of 22 glomeruli were seen, 2 of which showed cellular crescents and 10 of which showed fibrocellular crescents. Immunofluorescence of 8 glomeruli revealed diffuse linear glomerular basement membrane staining for IgA (3+), kappa (2+) and lambda (3+) light chains. A positive segmental granular-linear GBM staining is seen with IgG (1+) and C3( 2+). The other stains (IgM and C1q) are negative in glomeruli. The patient was started on cyclophosphamide and prednisone after 3 doses of methylprednisolone. He additionally received 7 sessions of plasmapheresis in an attempt to prevent progression to ESRD. Upon discharge creatinine was 4.69mg/dL and GFR was 13 , and he was ultimately started on hemodyalisis. In summary, anti-GBM disease mediated by IgA is incredibly rare, and cannot be screened for by routine ELISA designed to detect circulating IgG autoantibodies. Diagnosis relies on kidney biopsy and histopathology.
Sardarli K, Wu R, Cohen L. An interesting case of anti-glomerular basement membrane disease mediated by IGA autoantibodies. Am J Kidney Dis. 2023 Apr;81(4 Suppl.1):S8-S9. doi:10.1053/j.ajkd.2023.01.030