Selective IgA immune unresponsiveness to Proteus mirabilis fumarate reductase A-chain in rheumatoid arthritis.
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).


CONCLUSIONS
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.
Department of Medicine, Veterans Affairs Greater Los Angeles Health Care System, Sepulveda, CA 91343, USA. rweisbar@ucla.edu
Richard H
RH
Weisbart
Yoon
Y
Min
Andrew L
AL
Wong
Joanne
J
Kang
Suchada
S
Kwunyeun
Antony
A
Lin
Joon
J
Kim
Grace
G
Chan
Rika
R
Wakelin
William
W
Sohn
Sophia S
SS
Chang
Robert N
RN
Nishimura
D000328:Adult; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology*; D008969:Molecular Sequence Data; D011512:Proteus Infections / Q000150:complications / Q000276:immunology*; D011513:Proteus mirabilis / Q000201:enzymology / Q000276:immunology*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D013385:Succinate Dehydrogenase