Abstract
Rheumatoid Arthritis (RA) is a systemic, chronic inflammatory disease characterized by inflammation of synovial joints and production of autoantibodies such as Rheumatoid Factor and antibodies directed against modified proteins - i.e. anti-citrullinated peptides antibody (ACPA). Carbamylation, as a post translational modification, has been recently associated to RA since anticarbamylated protein antibodies (anti-CarP) have been detected in the sera of RA patients. The effect of treatment on anti-CarP level has been never addressed before. Through this study we aimed to investigate the short term effect of anti-TNF treatment with Etanercept on anti-CarP. We enrolled consecutive RA patients before starting treatment with Etanercept. Clinical data and serum samples were gathered from each patient at baseline and after 3 months of treatment. Disease activity was assessed at baseline and after 3 months by using the C-reactive protein - Disease Activity Score (DAS) 28. Sixty-three age and sex matched healthy donors served as controls. Anti-Car-P antibodies were investigated by immune-enzymatic assay. We enrolled 17 RA patients (F:M 15:2, mean age 44.1 ± 10.7 years, mean disease duration 7.9 ± 5.8 years). Six patients (35.3%) were positive for anti-CarP antibodies at baseline while three months after only 4 patients (23.5%) remained positive. Mean serum level of anti-CarP antibodies at baseline and after 3 months were: 253.0 ± 139.8AU/ml and 271.0 ± 132.4AU/ml respectively. Considering the persistently anti-CarP positive patients, the mean antibody titre increases from 386.2 ± 49.3AU/ml at baseline to 421.8 ± 144.0AU/ ml at follow up. The effect of anti-TNF treatment on autoantibody status is still controversial; in particular, data on ACPA variation during treatment are discordant. In our cohort of long standing RA patients, a short term course of Etanercept did not affect the antiCarP status. In conclusion, this pilot study demonstrated a slight reduction in the percentage of anti-CarP positive patients but an overall increase of antibody titre unrelated to the clinical response to TNF blockade was observed.
Highlights
Rheumatoid Arthritis (RA) is a systemic, chronic inflammatory disease mainly affecting the synovial joints, leading to cartilage and bone erosion
A distinctive feature of RA is the production of autoantibodies such as Rheumatoid Factor (RF) and antibodies directed against modified proteins - i.e. anti-citrullinated peptides antibody (ACPA)
A titration curve of two positive reference sera with medium-high ELISA immunoreactivity for anti-Car-Fetal Calf Serum (FCS) was carried out in order to show the performance of the test and to transform the absorbance of Car-FCS to arbitrary units per milliliter
Summary
Rheumatoid Arthritis (RA) is a systemic, chronic inflammatory disease mainly affecting the synovial joints, leading to cartilage and bone erosion. A distinctive feature of RA is the production of autoantibodies such as Rheumatoid Factor (RF) and antibodies directed against modified proteins - i.e. anti-citrullinated peptides antibody (ACPA). Post-translational modifications encompass several enzymatic or chemical reactions that modify and modulate protein functions. Carbamylation of proteins, leading to the production of homocitrulline, have been recently associated to RA. Anti-carbamylated proteins (anti-CarP) antibodies have been proposed as an additional biomarker of RA, especially in seronegative subjects and even in pre-clinical stage. As previously demonstrated for ACPA [1], anti-CarP antibodies seems to have a prognostic role since their presence is associated to a more severe and aggressive disease course [2]
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