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Selective IgA Immune Unresponsiveness to Proteus mirabilis Fumarate Reductase A-Chain in Rheumatoid Arthritis
RICHARD H. WEISBART, YOON MIN, ANDREW L. WONG, JOANNE KANG, SUCHADA KWUNYEUN, ANTONY LIN, JOON KIM, GRACE CHAN, RIKA WAKELIN, WILLIAM SOHN, SOPHIA S. CHANG, and ROBERT N. NISHIMURA ABSTRACT. Objective. To determine if selective immune unresponsiveness to microbial antigens is associated with predisposition to rheumatoid arthritis (RA). Methods. Proteins from Proteus mirabilis lysate were isolated by SDS-PAGE and examined by Western blotting for antibody responses in sera from patients with RA compared to healthy subjects and patients with psoriatic arthritis (PsA). Results. Although RA patients had marked IgA immune responses to many P. mirabilis proteins compared to healthy subjects, selective unresponsiveness was found in RA to a 66 kDa protein identified as fumarate reductase A-chain (FRD-A) by mass spectroscopy. This was confirmed in Western blots with recombinant FRD-A from P. mirabilis. IgA unresponsiveness to FRD-A was found in 21/59 (35.6%) RA patients compared to 7/63 (11.1%) healthy individuals (p < 0.01) and 6/52 (11.5%) patients with PsA (p < 0.01). IgA unresponsiveness to FRD-A was present in 20/46 (43.5%) RA patients with IgA rheumatoid factors (RF) compared to 1/13 (7.7%) without RF (p < 0.025). Conclusion. Our results identify a selective hole in the IgA immune repertoire for P. mirabilis FRD-A in a subset of IgA RF-positive patients with RA. (J Rheumatol 2005;32:1208–12) Key Indexing Terms: PROTEUS MIRABILIS From the Departments of Medicine, Veterans Affairs Greater Los Angeles Health Care System, Sepulveda; Department of Medicine, Olive View–UCLA Medical Center, Sylmar; and Department of Neurology, University of California, Los Angeles, California, USA. R.H. Weisbart, MD; J. Kang, MD; S. Kwunyeun, MD; A. Lin, MD; J. Kim, MD, PhD; G. Chan, BS; R. Wakelin, MS, Veterans Affairs Greater Los Angeles Health Care System; Y. Min, MD; A.L. Wong, MD, Olive View–UCLA Medical Center; W. Sohn, BA; S.S. Chang, BS; R.N. Nishimura, MD, University of California, Los Angeles. Address reprint requests to Dr. R. Weisbart, VAGLAHS (111S), 16111 Plummer Street, Sepulveda, CA 91343. E-mail: rweisbar@ucla.edu Accepted for publication March 17, 2005. |