Antibodies to porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives.
OBJECTIVE
Anticitrullinated protein antibodies (ACPA) are relatively specific for rheumatoid arthritis (RA), and predate disease. The oral pathogen Porphyromonas gingivalis may play a role in breaking immune tolerance to citrullinated antigens. We studied a cohort of patients with RA and their relatives looking for associations between anti-P. gingivalis antibodies and ACPA.


METHODS
Patients with RA (n = 82) and their relatives (n = 205) from a North American Native (NAN) population were studied, along with 47 NAN and 60 non-NAN controls. IgM and IgA rheumatoid factor (RF) were tested by nephelometry and ELISA. Second-generation anticyclic citrullinated peptide (anti-CCP2) isotypes and IgG anti-P. gingivalis lipopolysaccharides were tested by ELISA. HLA-DRB1 typing was performed by sequencing. Oral hygiene and smoking habits were assessed by questionnaires.


RESULTS
Autoantibody frequency in patients with RA and relatives: ACPA 91% vs 19%, respectively; IgM RF 82% vs 17%; IgA RF 48% vs 22%. Anti-P. gingivalis levels were higher in patients with RA compared to relatives and controls (p = 0.005) and higher in ACPA-positive patients with RA than in ACPA-negative patients with RA (p = 0.04) and relatives (p < 0.001), but comparable in RF-positive and RF-negative patients and relatives. Poor oral hygiene and smoking were prevalent, but with no clear association with autoantibodies. Relatives with 2 shared-epitope alleles were more likely to be ACPA-positive (OR 2.5, p = 0.02).


CONCLUSIONS
In a genetically predisposed population of NAN patients with RA and their relatives, anti-P. gingivalis antibodies were associated with ACPA. These findings suggest that immune responses to P. gingivalis may be involved in breaking immune tolerance to citrullinated antigens.
Hitchon
Carol A
CA
University of Manitoba, Winnipeg, Manitoba, Canada.
Chandad
Fatiha
F
Ferucci
Elizabeth D
ED
Willemze
Annemiek
A
Ioan-Facsinay
Andreea
A
van der Woude
Diane
D
Markland
Janet
J
Robinson
David
D
Elias
Brenda
B
Newkirk
Marianna
M
Toes
Rene M
RM
Huizinga
Tom W J
TW
El-Gabalawy
Hani S
HS
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D003731:Dental Caries / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007198:Indians, North American; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D012217:Rheumatoid Factor / Q000097:blood / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor