To determine if selective immune unresponsiveness to microbial antigens is associated with predisposition to rheumatoid arthritis (RA).
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).
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).
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.