AB0113 ANTI-CARBAMYLATED PROTEIN ANTIBODIES POSITIVITY AND DISEASE ACTIVITY IN HISPANIC PATIENTS WITH ESTABLISHED RHEUMATOID ARTHRITIS: AN OBSERVATIONAL STUDY

Background:Clinically relevant anti-carbamylated (anti-CarP) antibodies are detected in up to 45% of rheumatoid arthritis (RA) patients and are associated with severe radiological progression, higher disease activity, and significantly more disability when studied in early phases of arthritis.Objectives:We aimed to determine the prevalence of anti-CarP antibodies in Mexican Hispanics with established RA and to assess their relationship with disease activity.Methods:A cohort study was conducted in 278 patients with established RA during an 18-month follow-up. We measured IgG/IgM/IgA rheumatoid factor (RF), IgG anticitrullinated protein antibodies (ACPA) and IgG/IgM/IgA anti-CarP antibodies using enzyme-linked immunosorbent assay (ELISA). For disease activity, we performed the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR). Repeated measures one-way ANOVA was used to test the association between anti-CarP IgG antibody status and longitudinal DAS28-ESR scores. Patients were evaluated at baseline and at 6, 12, and 18 months during follow-up.Results:Anti-CarP IgG antibodies were positive in 47.8% of patients and, accounting for all isotypes, in 9.5% of patients with negative RF and ACPA. Triple antibody positivity was present in 42.6% of patients in our sample. Anti-CarP IgG antibody positivity did not show statistically significant differences in mean DAS28-ESR when compared to anti-CarP IgG antibody negative patients at baseline, 6, 12 or 18 months.Conclusion:Anti-CarP IgG antibodies are present in almost 50% of RA patients and, accounting for all isotypes, in 9% of RF and ACPA negative patients. Anti-CarP IgG antibody positivity was not associated to a higher disease activity measured by DAS28-ESR in Hispanic patients with established RA.References:Shi J, Knevel R, Suwannalai P, Van Der Linden MP, Janssen GMC, Van Veelen PA, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci U S A. 2011;108:17372–17377.Table 1.Anti-CarP antibody status by isotype in a cohort of 278 patients with established RA.Mean (SD)Antibody positivity,n (%)95% CIRF IgAa266.9 (460.5)155 (58.9)53.0 to 64.9RF IgMa406.8 (611.9)188 (71.5)66.0 to 77.0RF IgGa36.1 (249.6)44 (16.7)12.2 to 21.3ACPA IgGa191.01 (411.1)144 (54.8)48.7 to 60.8Anti-CarP IgAb212.9 (464.2)74 (26.6)21.4 to 31.8Anti-CarP IgMb381.6 (762)89 (32)26.5 to 37.5Anti-CarP IgGb227.5 (402.5)133 (47.8)41.9 to 53.8aData were available for 263 patients. Units are RU/mL. bData were available for 278 patients. Units are AU/mL. RF, rheumatoid factor; ACPA, anticitrullinated protein antibodies; Anti-CarP, anti-carbamylated protein antibodies; IgG, immunoglobulin; SD, standard deviation; 95% CI, 95% confidence intervals.Figure 1.Disclosure of Interests:David Vega-Morales Grant/research support from: This research was funded as an Investigator Initiated Study by UCB (IIS-2015-104068). The sponsor did not have any role in the design or outcomes of this study., Mario Alberto Garza Elizondo: None declared, Leendert A Trouw: None declared, Karina Itzel González Márquez: None declared, Ernesto Torres-Lopez: None declared, Myriam Eguia Bernal: None declared, SALVADOR AZAHEL LOREDO ALANIS: None declared, Tayde Sarahi Gracia-Arechiga: None declared, Brenda Roxana Vázquez Fuentes: None declared, Diana Daniela Castañeda Martínez: None declared, Martha Mariana Castañeda-Martínez: None declared, Cesar Vidal Solis: None declared, Andres Mendiola-Jimenez: None declared, Mario Cesar Salinas-Carmona: None declared, Pablo Herrera-Sandate: None declared, Alberto Cárdenas: None declared, Gerardo Eugenio Rodriguez-Sanchez: None declared, Dionicio Ángel Galarza-Delgado: None declared

Development of clinically apparent synovitis: a longitudinal study at the joint level during progression to inflammatory arthritis

IntroductionSubclinical inflammation, detected by MRI, in patients with arthralgia is predictive for development of inflammatory arthritis (IA). However, within patients that develop IA, the course of inflammation at the joint level during this transition is unknown. This longitudinal study assessed progression of inflammation at the joint level.Methods350 joints (unilateral metacarpophalangeals (MCPs), wrist, metatarsophalangeal (MTP) joints) of 35 patients presenting with clinically suspect arthralgia (CSA) that progressed to IA were studied at presentation with CSA and subsequently when clinical synovitis was first identified at joint examination (median time interval 17 weeks). At both time points, subclinical inflammation (bone marrow oedema, synovitis, tenosynovitis) was evaluated with MRI and joint examination was performed.ResultsAt presentation with CSA, 71 joints showed subclinical inflammation. During progression to IA, 20% of these joints had resolution of inflammation, 60% had persistent inflammation and 20% progressed to clinical synovitis. Of all joints that had developed clinical synovitis (n = 45), no prior subclinical inflammation was detected in 69%. Similar results were observed for anticitrullinated protein antibodies (ACPA)-positive and ACPA-negative patients.ConclusionsThis longitudinal study demonstrated moderate correlations between joints with subclinical inflammation and joints that developed clinical synovitis. These data imply that IA development is a more systemic rather than a locally outgrowing process.

Prevalence and clinical correlates of rheumatoid factor and anticitrullinated protein antibodies in patients with idiopathic inflammatory myopathy

ObjectiveAs rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM), little is known about their prevalence and clinical implications in this patient group. In antisynthetase syndrome (ASS), presence of ACPA is reportedly associated with more severe and erosive arthritis. We aim to retrospectively determine the prevalence of RF and ACPA in a cross-sectional cohort of 121 patients diagnosed with IIM and to assess clinical associations.MethodsSerum samples from 121 patients diagnosed with polymyositis (n=30), dermatomyositis (n=41), ASS (n=37), inclusion body myositis (n=1), necrotising autoimmune myopathy (n=5) or overlap myositis (n=7) were analysed. RF was evaluated by nephelometry (Immage 800, Beckman–Coulter); anti-CCP antibodies were identified using fluoro enzyme immunoassays (Immuno-Cap 250, Thermo Fisher). Values above 40 IU/mL and 7 U/mL were considered positive for RF and ACPA, respectively.ResultsThe prevalence of RF and ACPA was 9.09% and 4.96%, respectively. No significant differences were observed between RF/ACPA positive versus negative patients. There was a numerical trend for RF-positive IIM patients to be older and have lower forced expiratory volume in 1 s levels.ConclusionsRF and ACPA are prevalent in IIM, although we detected a lower prevalence than reported in previous studies. Presence of these antibodies in patients with IIM patients is not clinically relevant in our cohort.

Anticitrullinated Protein Antibodies Induce Inflammatory Gene Expression Profile in Peripheral Blood Cells from CCP–positive Patients with RA

Objective.Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA.Methods.To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)–positive patients with RA and healthy controls were cocultured in vitro with ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested whether the stimulatory effects induced by ACPA could be inhibited by the addition of a new multiepitope citrullinated peptide (Cit-ME).Results.We found that ACPA bind specifically to PBMC from CCP-positive patients with RA through the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4- to 13-fold increase) in PBMC derived from CCP-positive patients with RA. Moreover, ACPA upregulated IL-1β and IL-6 mRNA expression levels by 10- and 6-fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA, inhibited the ACPA-induced upregulation of IL-1β and IL-6 by 30%.Conclusion.ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA to decrease their pathogenic effects might provide a novel direction in developing therapeutic strategies for RA.

Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study

ObjectivesTo study whether oral contraceptive (OC) use or breastfeeding (BF) influence the risk of rheumatoid arthritis (RA), stratifying the cases by presence/absence of anticitrullinated protein antibodies (ACPA), and whether these factors interact with known risk factors in the development of ACPA-positive RA.MethodsWomen aged ≥18 years, participants in the population-based case–control Swedish Epidemiological Investigation of RA study (2641 cases/4251 controls), completed an extensive questionnaire regarding OC, BF and potential confounders. We calculated ORs, with 95% CIs, adjusted for age, residential area, smoking and alcohol consumption. Attributable proportion due to interaction (AP) was estimated to evaluate presence of interaction.ResultsCompared with never users, ever and past OC users had a decreased risk of ACPA-positive RA (OR=0.84 (95% CI 0.74 to 0.96); OR=0.83 (95% CI 0.73 to 0.95), respectively). No significant associations were found for ACPA-negative RA. Long duration of OC use (>7 years vs never use) decreased the risk of both ACPA-positive (p=0.0037) and ACPA-negative RA (p=0.0356).A history of long BF decreased the risk only of ACPA-positive RA in a dose-dependent manner (p=0.0086), but this trend did not remain after adjustments. A significant interaction was observed between the lack of OC use and smoking (AP=0.28 (95% CI 0.14–0.42)) on the risk of ACPA-positive RA. No interactions were found for BF.ConclusionsOC decreased the risk of RA, especially ACPA-positive RA, where an interaction with smoking was observed. A long duration of OC use decreased the risk of both disease subsets. We could not confirm an association between BF and a decreased risk of either ACPA-positive or ACPA-negative RA.