Presence Of anti-CarP Antibodies Research Articles

Anti-carbamylated protein antibodies in rheumatoid arthritis patients and their association with rheumatoid factor.

Objectives:To evaluate levels of anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and to determine their association with serological parameters and disease activity.Methods:A cross-sectional study involving 105 multiethnic RA patients (48 rheumatoid factor [RF]-positive and 57 RF-negative patients) was conducted at Hospital Universiti Sains Malaysia, Kelantan, Malaysia, from January 2015 to February 2016. Fifty healthy controls (HCs) were included. C-reactive protein (CRP), RF, anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies were measured. A health assessment questionnaire (HAQ) was administered to the study participants and 28-joint Disease Activity Score (DAS28) were obtained.Results:The level of anti-CarP antibodies was significantly increased in the RA patients compared with HCs (p=0.042). The presence of anti-CarP antibodies was significantly associated with RF (p=0.019) and the HAQ (p=0.010). A significant association between the presence of anti-CarP antibodies and the DAS28 was not found (p=0.632).Conclusion:Our study provides further evidence that the level of anti-CarP antibodies is significantly elevated in RA patients.

Anti-CarP antibodies as promising marker to measure joint damage and disease activity in patients with rheumatoid arthritis.

Anti-citrullinated protein antibodies (ACPA) are important serological markers in the diagnosis of rheumatoid arthritis (RA) and are part of the recent disease classification criteria. However, there is a strong need for reliable markers for measuring and predicting joint damage and disease activity. Recently, antibodies directed against carbamylated antigens (anti-CarP antibodies) were identified. A total of 120 RA patients were tested for anti-CCP antibodies using different methods and for anti-CarP antibodies using carbamylated fetal calf serum according to the method described by Shi et al. Additionally, ACPA fine specificities (to three citrullinated peptides) were measured. Disease activity was assessed at baseline using the disease activity score 28 (DAS28) in 80 patients. For 40 RA patients, joint erosion score (JES) was established. The median JES was 14.1 with a standard deviation of 11.5. Anti-CarP antibodies were correlated with joint erosion score (ρ = 0.34, 95% CI 0.03-0.59; p = 0.0332). No correlation between ACPA and joint erosion score was observed. No individual marker correlated with DAS28. When one ACPA peptide was combined with anti-CarP antibodies in a score (ACPA peptide 1 divided by anti-CarP), a statistically relevant correlation was found (p = 0.0264). In this small cohort, the presence of anti-CarP antibodies, but not ACPA correlate with joint erosion score. Anti-CarP antibodies combined with ACPA fine specificities correlated with DAS28. Therefore, anti-CarP antibodies might represent a promising marker to predict joint damage and disease activity in RA patients.

FRI0046 Anti-Carbamylated Protein Antibodies Precede the Onset of Symptoms of Rheumatoid Arthritis in A Swedish Biobank Cohort

BackgroundAntibodies against citrullinated peptides of several specificities (ACPAs) have been found to predate the onset of symptoms of rheumatoid arthritis (RA) by years. The presence of a new auto-antibody system,...

Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage

Autoimmune responses against posttranslationally modified antigens are a hallmark of several autoimmune diseases. For example, antibodies against citrullinated protein antigens (ACPA) have shown their relevance for the prognosis and diagnosis of rheumatoid arthritis (RA), and have been implicated in disease pathogenesis. It is conceivable that other autoantibody systems, recognizing other posttranslationally modified proteins, are also present in RA. Here, we describe the presence of an autoantibody system that discriminates between citrulline- and homocitrulline-containing antigens in the sera of RA-patients. IgG antibodies recognizing carbamylated (homocitrulline-containing) antigens were present in sera of over 45% of RA-patients. Likewise, anticarbamylated protein (anti-CarP) IgA antibodies were observed in 43% of RA-sera. ACPA and anti-CarP antibodies are distinct autoantibodies because, in selected double-positive patients, the anti-CarP antibody binding to carbamylated antigens could be inhibited by carbamylated antigens, but not by control or citrullinated antigens. Similarly, ACPA-binding to citrullinated antigens could only be inhibited by citrullinated antigens. In line with this observation, 16% of ACPA-negative RA-patients, as measured by a standard ACPA assay, harbored IgG anti-CarP antibodies, whereas 30% of these patients tested positive for IgA anti-CarP antibodies. The presence of anti-CarP antibodies was predictive for a more severe disease course in ACPA-negative patients as measured by radiological progression. Taken together, these data show the presence of a unique autoantibody system recognizing carbamylated, but not citrullinated, protein antigens. These antibodies are predictive for a more severe clinical course in ACPA-negative RA-patients, indicating that anti-CarP antibodies are a unique and relevant serological marker for ACPA-negative RA.

A time-study analysis to evaluate albumin carbamylation in vitro

Carbamylation is a non-enzymatic post-translational modification in which cyanate binds to molecules containing primary amine or thiol groups and forms carbamyl groups. Cyanate is in equilibrium with urea in body fluid and increased carbamylation was first reported in patients with increased urea levels such as patients suffering renal diseases. Next, increased carbamylation related to inflammation has also been described in other conditions such as cardiovascular disease.Recently, a new consequence of carbamylation has been observed: induction of an autoantibody response. We identified anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and in patients having ‘pre-RA’ symptoms, arthralgia. The presence of anti-CarP antibodies in arthralgia patients is associated with an increased risk of developing RA. The presence of anti-CarP antibodies in RA patients is associated with more severe joint damage in RA patients who do not have anti-citrullinated protein antibodies. It is currently unknown to what extent carbamylation and/or the formation of anti-CarP antibodies contributes to the disease processes of chronic diseases such as renal diseases, cardiovascular diseases and RA. This review summarizes the current knowledge on carbamylation and the formation of anti-CarP antibodies and discusses their possibly important implications.