Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.

Anticyclic Citrullinated Peptide Antibodies 3.1 and Anti-CCP-IgA Are Associated with Increasing Age in Individuals Without Rheumatoid Arthritis

Objective.We investigated the association of age and anticyclic citrullinated peptide antibodies (anti-CCP) in subjects without rheumatoid arthritis (RA).Methods.Serum was tested for anti-CCP3.1 (IgG/IgA) in 678 first-degree relatives (FDR) of patients with RA and 330 patients with osteoarthritis (OA). Individual isotypes (anti–CCP-IgA and anti–CCP-IgG) were also tested in all FDR.Results.In FDR, increasing age was significantly associated with positivity for anti-CCP3.1 (per year, OR 1.03) and anti–CCP-IgA (per year, OR 1.05) but not anti–CCP-IgG. In FDR and OA subjects, anti-CCP3.1 prevalence was significantly increased after age 50 years.Conclusion.Increasing age in individuals without RA should be considered in the interpretation of anti-CCP3.1 positivity.

Repair of Erosions in Patients with Rheumatoid Arthritis

Objective.The aim of this study was to examine the occurrence of repair in a cohort of conventionally treated patients with early rheumatoid arthritis over 8 years.Methods.There were 395 patients included in the BARFOT study having radiographs of hands and feet at inclusion, and at 1, 2, 5, and 8 years, which were chronologically scored for erosions by the Sharp/van der Heijde method. An erosion with repair was defined as an erosion that has become partially or totally filled, with or without sclerosis.Results.Erosions with repair were observed in 64 patients (16%) at 1 year, 113 (29%) at 2 years, 142 (36%) at 5 years, and 200 (51%) at 8 years. At the 1-year visit, 13% of the patients with at least 1 new erosion showed repair versus 3% of the patients with no new erosions (p = 0.001). At 2, 5, and 8 years the corresponding figures were 22% and 6%, 28% and 8%, and 39% and 11%, respectively (all p = 0.001). The sum of all repaired erosions correlated strongly with the sum of all erosions and with the sum of all erosion scores (ρ = 0.79 and 0.77). Presence of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) was significantly associated with both new erosions and repair.Conclusion.Repair was more common than previously described. The frequency of repair increased over time and was associated with the number of erosions. RF- and anti-CCP–positivity, patient age, and presence of erosions at baseline were independent predictors of repair.

Anticyclic Citrullinated Peptide Antibodies and Rheumatoid Factor as Risk Factors for 10-year Cardiovascular Morbidity in Patients with Rheumatoid Arthritis: A Large Inception Cohort Study

Objective.To determine whether anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) are risk factors for 10-year cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).Methods.Analyses were performed using data from the Nijmegen early RA inception cohort, in which patients with newly diagnosed RA, consecutively included since 1985, were regularly followed up. Anti-CCP and RF were determined at baseline (diagnosis). Outcome was the first cardiovascular disease (CVD) event [ischemic heart disease, nonhemorrhagic cerebrovascular accident (CVA), or peripheral artery disease (PAD)] after baseline as retrieved from physician diagnosis. Fatality was checked against death certificates. Cox regression including correction for baseline confounders was performed to estimate the effect of anti-CCP, RF, and their interaction on 10-year CVD-free survival.Results.Of 929 patients included, 628 were anti-CCP–positive and 697 were RF-positive. During followup, with a median of 7.5 years, 162 CV events were observed (101 ischemic heart disease, 45 CVA, and 16 PAD), of which 15 were fatal. The HRadjusted for anti-CCP was 1.17 (95% CI 0.82–1.67) and the HRadjusted for RF was 1.52 (95% CI 1.00–2.30). The association of RF positivity with CVD was even stronger in the anti-CCP–negative patients: HRadjusted 2.09 (95% CI 1.18–3.71). There was no significant interaction (p = 0.098) between anti-CCP and RF.Conclusion.Rather than anti-CCP, presence of RF was associated with CVD in this cohort of patients with RA.

Clinical and Serological Analysis of Patients with Positive Anticyclic Citrullinated Peptide Antibodies Referred Through a Rheumatology Central Triage System

Objective.Anticitrullinated protein antibodies (ACPA) are a highly specific and sensitive biomarker for the diagnosis of rheumatoid arthritis (RA). Some patients who were found to have a positive ACPA test were referred to our Rheumatology Central Triage (CT; Calgary, Alberta, Canada) for assessment by a rheumatologist. The objectives of our study were to determine the clinical accuracy of ACPA in establishing a diagnosis of RA in a real-time clinical setting.Methods.Cases that met 3 criteria were included in the study: (1) referred to the CT over 3 calendar years (n = 20,389), (2) reason for referral was a positive ACPA test (n = 568), and (3) evaluated by a certified rheumatologist (n = 314). An administrative serological database was used to retrieve specific ACPA results.Results.Of patients referred through our CT for evaluation of a positive ACPA test, 57.6% received a diagnosis of RA; the remainder had a variety of other diagnoses, some of which might be considered early RA (9%). The predictive values of ACPA for the diagnosis of RA were increased when rheumatoid factor (RF) results were included in the analysis. When definite and possible RA were combined and the prevalence of moderate/high ACPA was compared to all other individuals, the positive and negative predictive values for moderate/high ACPA for RA were 74.3% and 68.4%, respectively.Conclusion.About 58% of patients with a positive ACPA referred through a triage system for a rheumatologist opinion received a diagnosis of RA at their first visit. RF provides additional useful information to guide the diagnosis and urgency of referral.

Anti-carbamylated Protein Antibodies Are Present Prior to Rheumatoid Arthritis and Are Associated with Its Future Diagnosis

Objective.Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel.Methods.Stored pre-RA diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and RF isotypes [immunoglobulin M (IgM), IgG, and IgA]. Positivity for all antibodies was determined as ≥ 2 SD of log-transformed means from controls. Relationships between autoantibodies and future RA were assessed in prediagnosis serum for all RA cases compared to controls using sensitivity, specificity, and logistic regression. Differences in diagnostic accuracy between antibody combinations were assessed using comparisons of area under the curves (AUC).Results.Anti-CarP-FCS was 26% sensitive and 95% specific for future RA, whereas anti-CarP-Fib was 16% sensitive and 95% specific for future RA. Anti-CarP-FCS positivity was associated with future RA, while anti-CarP-Fib trended toward association. The antibody combination of anti-CCP2 and/or ≥ 2 RF (RF-Neph and/or RF-isotypes) resulted in an AUC of 0.72 for future RA, where the AUC was 0.71 with the addition of anti-CarP-FCS to this prior combination.Conclusion.Adding anti-CarP-FCS to antibody combinations did not improve AUC. However, anti-CarP-FCS was associated with future onset of RA, and was present in prediagnosis serum in ∼10% of RA cases negative for anti-CCP2 but positive for RF.