Session Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Background/Purpose: Three prior studies have demonstrated an increased frequency of antibody responses to P. gingivalis (Pg), a leading agent of periodontal disease (PD), in RA patients, lending further evidence for a “mouth-joint connection” in RA pathogenesis. However, in these studies, patients had longstanding disease and were receiving DMARD therapy, which may affect serum antibody responses to Pg as well as infection with PD pathogens. Our goal was to determine the frequency of Pg antibody responses and their clinical associations early in the course of RA, prior to DMARD therapy.
Methods: We have established an early RA cohort study. To date, 45 adult patients with <1 year of symptoms have been enrolled prior to DMARD treatment and enrollment is ongoing. Sera from the early RA patients and 60 healthy controls were tested for Pg IgG antibodies by ELISA using sonicate antigen of whole Pg (ATCC 33277). A positive Pg antibody response was defined as >2SD above the mean absorbance of the 60 control subjects.
Results: The 45 early RA patients were typical of an RA cohort; 73% were female and 80% had positive test results for anti-CCP antibodies or rheumatoid factor (RF). Thirteen (29%) had a smoking history, but only 6 (13%) were current smokers. At study entry, 14 of the 45 patients (31%) had positive IgG antibody responses to Pg and the levels were significantly higher compared to healthy controls (P<0.0001). History of smoking was slightly lower in patients with Pg antibodies (3/13, 23%) than in those without such antibody responses (13/32, 41%), and median levels of Pg antibodies were not different between these groups. At study entry, early RA patients with Pg antibodies tended to have higher DAS-28-ESR scores (median values, 5.2 versus 4.3), more frequent anti-CCP antibody responses (86% versus 68%), and higher ESR values (median values 35 versus 20 mm/h, P=0.05) than those without Pg antibodies. Moreover, the magnitude of Pg antibody responses correlated directly with anti-CCP antibody levels (R2=0.147, P=0.009) and ESR values (R2=0.179, P=0.004), while showing no correlation with RF or CRP levels. During 12 months of DMARD therapy, DAS-28-ESR scores and Pg antibody responses declined in most patients, and no patient who had a negative Pg antibody response at entry became seropositive. At 12 months, there was still a trend toward higher DAS-28-ESR scores in patients with Pg antibody responses than those without Pg antibody (median score, 3.9 versus 2.4, P=0.08), and fewer patients in the Pg+ group achieved DAS remission (31% versus 56%).
Conclusion: A subset of patients with early untreated RA had IgG antibody reactivity to Pg. The high Pg antibody responses at this time demonstrate that immunosuppressive therapy does not explain the Pg antibody reactivity. In these patients, higher anti-CCP antibody responses and ESR values suggested that Pg infection may be associated with a specific inflammatory response. Finally, Pg antibody positivity was associated with a trend toward greater disease activity and less likelihood of achieving remission by 12 months. These findings support a role for Pg in both the initiation and persistence of disease activity in a subset of patients with early RA.
S. L. Arvikar,
NIH, Arthritis Foundation,
D. S. Collier,
M. C. Fisher,
Novartis Pharmaceutical Corporation,
A. C. Steere,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/porphyromonas-gingivalis-antibody-responses-and-clinical-associations-in-patients-with-early-rheumatoid-arthritis/