Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.
Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (n = 142), chronic inflammatory disease (CIRD, n = 86), and clinically healthy subjects (CHS, n = 56) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis.
We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.
BackgroundSyndecans includes a group of proteins from the cell-surface heparan-sulfate proteoglycan family, with a relevant role in chronic inflammation of synovial tissue in patients with rheumatoid arthritis (RA) participating in the cell-matrix and cell-cell interactions. Syndecans are differentially expressed in the synovial tissue: syndecan-1 (SDC-1) is expressed mainly in mononuclear cells, syndecan-3 (SDC-3) is mainly expressed by synovial endothelial cells and syndecan-4 (SDC-4) is expressed by B lymphocytes regulating B cell development and survival. Currently, there is strong evidence that antibodies directed to citrullinated protein antigens (ACPAs) are associated with a more severe disease in RA. Nevertheless, to date, there is a lack of information about the relation between serum syndecan levels and serum concentrations of rheumatoid factor (RF) and ACPAs.ObjectivesTo evaluate the association between serum SDC-1, SDC-3 and SDC-4 levels with serum concentrations of RF and ACPAs.MethodsEighty-one, patients with RA were included. We assessed clinical characteristics including disease activity by DAS-28, functioning by HAQ-Di. Serum concentrations of RF were measured by nephelometry, two ACPAs were measured: anti-CCP2 and anti-mutated citrullinated vimentin (anti-MCV) antibodies using ELISA. Serum levels of SDC-1, SDC-3 (ng/mL) and SDC-4 (pg/mL) were measured by ELISA. We compared the serum levels of these syndecans in the ACPA+ group (group 1) versus ACPA- group (group 2) with Student t-test. A correlation analysis (Pearson tests) was performed to identify the strength of association between concentrations of syndecans with concentrations of ACPAs and other variables.ResultsPatients with RA had a mean age of 50±11 yrs, 75% were RF+ and 64% were ACPA+. In patients with ACPAs+ were observed higher serum concentrations of SDC-3 (p=0.003) and SDC-4 (p<0.001). SDC-1 correlated significantly with anti-MCV (r=0.53, p<0.001). Serum concentrations of SDC-3 correlated significantly with anti-CCP titres (r=0.53, p=0.003) and anti-MCV (r=0.46, p=0.02); whereas SDC-4 levels correlated significantly with anti-CCP titres (r=0.61, p<0.001) and RF (r=0.53, p=0.003). Additionally, serum SDC-1 levels correlated with decrement in response to treatment with synthetic DMARDs (r=-0.25, p=0.026). SDC-1 did not correlate with serum SDC-3 (p=0.8) and SDC-4 (p=0.8); whereas serum SDC-3 and SDC-4 had a strong correlation (r=0.8, p<0.001).ConclusionsSerum SDC-3 and SDC-4 are increased in ACPA-positive RA patients. These data suggest that syndecans might be useful as serum biomarkers for discriminate a group of patients with RA and more severe disease.References Patterson AM, et al. Ann Rheum Dis. 2008 May;67(5):592–601.Endo T, et al. Arthritis Rheumatol. 2015 Sep;67(9):2512–22. AcknowledgementsThis project was supported by a grant from the Fondo de Investigacion en Salud del Instituto Mexicano del Seguro Social: FIS/IMSS/PROT/G15/1448.Disclosure of InterestN. Rodriguez-Jimenez: None declared, E. Cardona-Muñoz: None declared, J. Gam...
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