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

Rui Yang^*, Thomas Hellmark, Juan Zhao^*, Zhao Cui^*, Marten Segelmark, Ming-hui Zhao^* and Hai-yan Wang^*

^* Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University; and Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China; and Department of Nephrology, Clinical Sciences, Lund, Lund University, Lund, Sweden

Address correspondence to: Dr. Ming-hui Zhao, Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, and Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P.R. China. Phone: +86-10-66551736; Fax: +86-10-66551055; mhzhao{at}bjmu.edu.cn

Received for publication November 7, 2006. Accepted for publication January 15, 2007.

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.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673