Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis.
OBJECTIVE
To examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA).


METHODS
Study participants included the following: 1) a cohort enriched in subjects with HLA-DR4 and 2) subjects at risk of RA by virtue of having a first-degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti-citrullinated protein antibody (ACPA; by second-generation anti-cyclic citrullinated peptide antibody enzyme-linked immunosorbent assay [ELISA]) and rheumatoid factor (RF; by nephelometry or ELISA for IgA, IgM, or IgG isotype). Individuals were considered autoantibody positive (n = 113) if they had ≥1 RA-related autoantibody; individuals were further categorized as high risk (n = 38) if they had ACPA or positive findings ≥2 assays for RF. Autoantibody-negative individuals (n = 171) served as a comparator group. Antibody to P gingivalis, P intermedia, and F nucleatum were measured. Associations of bacterial antibodies with group status were examined using logistic regression.


RESULTS
Anti-P gingivalis concentrations were higher in high-risk (P = 0.011) and autoantibody positive group (P = 0.010) than in the autoantibody negative group. There were no group differences in anti-P intermedia or anti-F nucleatum concentrations. After multivariable adjustment, anti-P gingivalis concentrations (but not anti-P intermedia or anti-F nucleatum) were significantly associated with autoantibody-positive and high-risk status (P < 0.05).


CONCLUSIONS
Immunity to P gingivalis, but not P intermedia or F nucleatum, is significantly associated with the presence of RA-related autoantibodies in individuals at risk of RA. These results support the hypothesis that infection with P gingivalis may play a central role in the early loss of tolerance to self antigens that occurs in the pathogenesis of RA.
Omaha VA Medical Center, NE, USA. tmikuls@unmc.edu
Ted R
TR
Mikuls
Geoffrey M
GM
Thiele
Kevin D
KD
Deane
Jeffrey B
JB
Payne
James R
JR
O'Dell
Fang
F
Yu
Harlan
H
Sayles
Michael H
MH
Weisman
Peter K
PK
Gregersen
Jane H
JH
Buckner
Richard M
RM
Keating
Lezlie A
LA
Derber
William H
WH
Robinson
V Michael
VM
Holers
Jill M
JM
Norris
D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology; D001323:Autoantibodies / Q000097:blood*; D016866:Bacteroidaceae Infections / Q000453:epidemiology* / Q000276:immunology; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D012307:Risk Factors; D016036:Seroepidemiologic Studies
D000907:Antibodies, Bacterial; D001323:Autoantibodies