Coexistence of Anti-Glomerular Basement Membrane Antibodies and Anti-Neutrophil Cytoplasmic Antibodies in a Child With Human Leukocyte Antigen Susceptibility and Detailed Antibody Description: A Case Report

Abstract

Anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis both could cause rapidly progressive glomerulonephritis. The coexistence of ANCAs and anti-GBM antibodies was known as "double positive," which was extremely rare in children. We report a pediatric case with coexistence of ANCAs and anti-GBM antibodies. A 6-year-old girl presented with acute renal failure, hematuria, proteinuria, and oliguria. She was double positive of ANCAs specific to myeloperoxidase, and anti-GBM antibodies. Kidney biopsy confirmed linear immunoglobulin (Ig)G deposit along GBM and 100% of crescent formation in glomeruli; among them 83.3% were cellular crescents. Human leukocyte antigen (HLA) gene typing showed DRB1*1501, an allele strongly associated with anti-GBM disease, and DRB1*0405, an independent risk factor for renal failure in patients with ANCA-associated vasculitis. The titer of anti-GBM antibodies was 1:800, and the predominant IgG subclass was IgG1, which was closely related with severe kidney injury and worse outcome. The target antigen of anti-GBM antibodies was restricted on the noncollagen domain 1 of the α3 chain of type IV collagen (α3[IV]NC1), with recognitions to both epitopes, EA (α317-31) and EB (α3127-141). This is the first reported pediatric case with coexistence of ANCAs and anti-GBM antibodies, in which the HLA typing and immunologic characters of autoantibodies were identified. The findings on this early-onset patient are meaningful for understanding the mechanisms of both anti-GBM disease and ANCA-associated vasculitis.

FIGURE 1

Light microscopy findings on renal biopsy: fibrocellular crescent formation (×200).

FIGURE 2

The treatments and follow-up of the patient. Plasmapheresis 8 times (fresh-frozen plasma1000 mL/time) was performed to remove antibodies from circulation. Three courses of methylprednisolone pulse therapy were applied, with each course of 500 mg/day for 3 days. Cyclophosphamide was given 2 times at doses 0.12 g and 0.35 g separately.