Antigen and Epitope Specificity of Anti-Glomerular Basement Membrane Antibodies in Patients with Goodpasture Disease with or without Anti-Neutrophil Cytoplasmic Antibodies

2007-03-27

Goodpasture disease (GP) is defined by the presence of anti–glomerular basement membrane (anti-GBM) antibodies and rapidly progressive glomerulonephritis. Besides anti-GBM, many patients with GP produce anti-neutrophil cytoplasmic antibodies (ANCA). For elucidation of the pathophysiologic significance of ANCA in this setting, epitope and antigen specificity of the anti-GBM antibodies and antigen specificity of ANCA were studied. Bovine testis (IV)NC1 (tNC1); recombinant human 1, 3, 4, and 5(IV)NC1 (r1 through r5); and three chimeric proteins that contain previously defined epitope regions designated E_A, E_B, and S2 were used to examine the anti-GBM antibodies by ELISA in 205 Chinese patients with GP with or without ANCA. In the 205 anti-GBM antibody–positive sera, 63 (30.7%) were also ANCA positive (61 myeloperoxidase-ANCA and six proteinase 3–ANCA, four being triple positive). All 205 sera recognized tNC1 and r3(IV)NC1. In the double-positive group, 54.0, 66.7, 71.4% of the sera could recognize r1, r4, and r5, respectively, compared with 49.3, 60.6, and 55.6% for patients with anti-GBM antibodies alone. The levels of the antibodies to r3, tNC1, and the 3/1 ratio were lower in the double-positive group than that in patients with anti-GBM antibody alone (P < 0.05). Most of the sera could recognize the epitope regions E_A, E_B, and S2, but the absorbance values to E_A, E_B, and S2 were lower in double-positive group (P < 0.05). Double-positive patients had a broader spectrum of anti-GBM antibodies and lower levels of antibodies against 3(IV)NC1 compared with that of patients with anti-GBM antibodies alone.

Journal of the American Society of Nephrology Clinical Immunology and Pathology

Antigen and Epitope Specificity of Anti-Glomerular Basement Membrane Antibodies in Patients with Goodpasture Disease with or without Anti-Neutrophil Cytoplasmic Antibodies