title: 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.
authors.affiliation: From the Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China (L-jX, ZC, X-yJ, M-hZ); Department of Nephrology, Beijing Children's Hospital affiliated to Capital Medical University (ZC, X-rL); Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China (L-jX); and Peking-Tsinghua Center for Life Sciences, Beijing, PR China (M-hZ).
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Xie
authors.forename: Zhao
authors.initials: Z
authors.lastname: Cui
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Jia
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002648:Child; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051437:Renal Insufficiency / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; C051951:antiglomerular basement membrane antibody