title: Association of epitope spreading of antiglomerular basement membrane antibodies and kidney injury.
abstract: OBJECTIVE
  Antiglomerular basement membrane autoantibodies are pathogenic in antiglomerular basement membrane disease with two major epitopes, E(A) and E(B), on α3 chain of type IV collagen. This study investigated the epitope spectrum of antiglomerular basement membrane autoantibodies, aiming to identify the association between epitope specificity and kidney injury.
  
  
  METHODS
  All 108 patients with antiglomerular basement membrane disease and complete clinical data were divided into three groups according to renal dysfunction: mild group (n=20) with serum creatitine≤1.5 mg/dl; moderate group (n=22) with serum creatinine=1.5-6.8 mg/dl; severe group (n=66) with serum creatitine≥6.8 mg/dl. Epitope spectrums of antibodies were determined by ELISA, and their associations with kidney damage were analyzed. Sequential serum samples in 40 patients were examined during disease courses.
  
  
  RESULTS
  E(A) and E(B) were recognized in 79.6% and 72.2% of patients, respectively. E(A) and E(B) reactions were the lowest in the mild group and higher in the moderate group (E(A): 35.0% versus 81.8%, P=0.002; E(B): 15.0% versus 68.2%, P=0.001). They were the highest in the severe group (E(A): 92.4%, P=0.31; E(B): 90.9%, P=0.02). Close association was observed between renal injury and E(A) and E(B) reactions. Multivariate Cox regression analysis showed that E(B) reaction was an independent risk factor for renal failure (hazard ratio=6.91, P=0.02). The recognition for non-E(AB) remained low among groups. No augmentation of epitope spectrum was shown in serial serum samples.
  
  
  CONCLUSIONS
  Intramolecular epitope spreading might occur before the onset of human antiglomerular basement membrane disease. The autoimmunity to E(A) and E(B), especially E(B), was crucial for kidney dysfunction.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Jun-liang
authors.initials: JL
authors.lastname: Chen
authors.forename: Shui-yi
authors.initials: SY
authors.lastname: Hu
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Jia
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Cui
authors.forename: Ming-hui
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019867:Anti-Glomerular Basement Membrane Disease / Q000453:epidemiology* / Q000276:immunology* / Q000401:mortality; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D024141:Collagen Type IV / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D000939:Epitopes; C051951:antiglomerular basement membrane antibody; C057112:type IV collagen alpha3 chain