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.