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.
Weisbart
Richard H
RH
Department of Medicine, Veterans Affairs Greater Los Angeles Health Care System, Sepulveda, CA 91343, USA. rweisbar@ucla.edu
Min
Yoon
Y
Wong
Andrew L
AL
Kang
Joanne
J
Kwunyeun
Suchada
S
Lin
Antony
A
Kim
Joon
J
Chan
Grace
G
Wakelin
Rika
R
Sohn
William
W
Chang
Sophia S
SS
Nishimura
Robert N
RN
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