Association of epitope spreading of antiglomerular basement membrane antibodies and kidney injury

Clin J Am Soc Nephrol. 2013 Jan;8(1):51-8. doi: 10.2215/CJN.05140512. Epub 2012 Oct 18.

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Glomerular Basement Membrane Disease / epidemiology*
  • Anti-Glomerular Basement Membrane Disease / immunology*
  • Anti-Glomerular Basement Membrane Disease / mortality
  • Antibody Specificity / immunology
  • Autoantibodies / blood*
  • Autoantigens / immunology*
  • Collagen Type IV / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • Female
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / immunology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Seroepidemiologic Studies
  • Young Adult

Substances

  • Autoantibodies
  • Autoantigens
  • Collagen Type IV
  • Epitopes
  • antiglomerular basement membrane antibody
  • type IV collagen alpha3 chain