Assessment of anti-CarP antibodies, disease activity and quality of life in rheumatoid arthritis patients on conventional and biological disease-modifying antirheumatic drugs (original) (raw)
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Arthritis Research & Therapy, 2016
Background: Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs). Methods: Serum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated. Anti-CarP were detected using carbamylated fetal calf serum as the antigen. ACPAs were detected using second-generation ELISA and IgM RF was assessed as part of routine analysis. Results: Anti-CarP antibodies were detected in 117 patients with RA (34.4%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sjögren syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF was 46.8%, 61.8% and 64.4%, respectively and specificity was 91.95%, 89.93% and 76.51%, respectively. Conclusions: The present study extends the knowledge of anti-CarP antibodies, confirming previous data on the diagnostic accuracy of anti-CarP in RA in a large cohort of Italian patients. Anti-CarP antibodies demonstrated relatively low sensitivity and slightly higher specificity compared to ACPA and RF. Even if predominantly present in RA, anti-CarP was detected in a variable percentage of patients with other autoimmune rheumatic diseases and their generation could be attributed to the inflammatory status; the clinical relevance of anti-CarP antibodies in these latter patients should be further determined.
Clinical and Experimental Rheumatology
Objective Carbamylation is an irreversible post-translational modification of proteins. The presence of anti-carbamylated protein antibodies (anti-CarP) has been observed in rheumatoid arthritis (RA). This study was focused to verify whether anti-CarP antibodies can be used as a predictive factor of clinical response to abatacept (CTLA4-Ig) in RA patients. Methods Sixty RA patients treated with abatacept were enrolled. A home-made ELISA for anti-CarP and a commercial anti-CCP3.1 kit for anti-citrullinated proteins antibodies (anti-CCP) were applied to determine serum levels every six months of therapy. Rheumatoid factor (RF) was also tested. Results Anti-CarP positive patients (n=18) were younger (p=0.01) and with a longer disease duration (p=0.05) when compared to anti-CarP negative patients (n=42) at baseline. Considering the entire cohort, a significant reduction of anti-CarP titre after twelve-months of treatment was shown (p<0.01). A significant reduction of Disease Activity Score (DAS) 28-C-reactive protein (CRP) in the first six months of therapy was found in the subgroup of anti-CarP positive patients in comparison with the negative ones (p=0.003). No significant results were found by dividing the cohort using the positivity to anti-CCP and/or RF. Conclusion Earlier onset and a longer disease duration in anti-CarP positive patients might suggest they are specific risk factors for RA in this subgroup of patients. The correlation between the anti-CarP positivity at baseline and the reduction of disease activity during the first six months of treatment with abatacept allowed us to hypothesise that anti-CarP antibodies, but not anti-CCP and/or RF, could be used as a good clinical response predictor.
The Journal of rheumatology, 2015
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. 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). Anti-CarP-FCS was...
Arthritis & Rheumatology
Objective. To assess the prevalence of anti-carbamylated protein (anti-CarP) antibodies in a French cohort of patients with early arthritis and to investigate their association with clinical features, final diagnosis, prognosis, and comorbidities. Methods. The presence of anti-CarP antibodies among patients with early arthritis in the French Etude et Suivi des Polyarthrites Indiff erenci ees R ecentes (ESPOIR) cohort (n = 720) was determined using enzyme-linked immunosorbent assay. We investigated the prevalence of anti-CarP antibodies in different patient subgroups stratified according to anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) status. Diagnostic and prognostic values of the test were evaluated in this population. Results. Anti-CarP antibodies were present in approximately one-third of the patients (32.6%) and in 23.6% of the patients who were seronegative for both RF and ACPA. Anti-CarP positivity was associated with a more active disease status at baseline and over time. Anti-CarP-positive patients had a significantly higher Disease Activity Score in 28 joints using the erythrocyte sedimentation rate at month 36 than anti-CarP-negative patients (3.1 AE 0.11 versus 2.8 AE 0.06; P = 0.03). Anti-CarP-positive early arthritis was associated with a higher risk of developing erosions after 96 months of follow-up (55.6% of anti-CarP-positive patients versus 37.3% of anti-CarP-negative patients) (odds ratio 2.1 [95% CI 1.2-3.6]; P = 0.009). This association was particularly true when anti-CarP was associated with ACPA positivity. Moreover, ACPA positivity alone in early arthritis was not associated with a higher risk of erosive evolution. Conclusion. Our findings indicate that anti-CarP antibodies are present in one-third of patients with early arthritis and in one-fourth of the RF-negative and ACPA-negative patients. They are particularly associated with a more severe radiographic outcome. Anti-CarP antibody positivity may help to accurately identify those at risk of erosive evolution in an early arthritis population. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the 2 main autoantibodies associated with rheumatoid arthritis (RA) (1). ACPAs and/or RF are detected in~70-80% of RA patients (2). Approximately one-third of patients with established RA do not express RF or ACPAs.
Modern Rheumatology, 2021
Objectives We aimed to determine the prevalence of anti-carbamylated protein (anti-CarP) antibodies in Mexican Hispanics with established rheumatoid arthritis (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. Tri...
PloS one, 2016
A large fraction of the patients with rheumatoid arthritis (RA) develop specific autoantibodies, which until recently were only of two types, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). We aimed to replicate important findings about a recently described third type of specific autoantibodies, anti-carbamylated protein (anti-CarP) antibodies, because they have been described based only in the homemade ELISA from a single laboratory. Our study included 520 patients with established RA and 278 healthy controls of Spanish ancestry and it was done with an independently performed ELISA. The prevalence and pattern of environmental, clinical and genetic associations of the anti-CarP antibodies were similar to the previously described. Notably, the presence and titers of anti-CarP correlated with the presence and titers of ACPA, but the anti-CarP antibodies did not share the known genetic and exposure risk factors of the ACPA. In addition, anti-CarP antibodies wer...
Open Access Rheumatology: Research and Reviews
Background and objective: Anti-carbamylated protein antibodies (anti-CarP Ab) represent a novel kind of autoantibodies specificity detectable in the sera of patients with rheumatoid arthritis (RA). They have been recently reported to be associated with increased mortality in Spanish patients with RA. The aim of our study was to compare the incidence mortality rates (IMRs) detected in RA patients from a tertiary Italian center with those reported in other European tertiary centers and to evaluate the putative role of anti-CarP Ab in modulating the low IMR detected in our patients. Methods: Clinical charts of patients consecutively admitted to our center, from January 1, 2008, to December 31, 2014, were retrospectively reviewed. The mortality rate (expressed as the number of deaths in the cohort divided by the number of years of IMR follow-up) and causes of death were assessed at December 31, 2015. Sera of 61 patients, representative of the whole cohort, collected at the time of admission to our center were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab in our series were compared with those reported in other European cohorts. Results: We observed 608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy and the Spanish cohort, while only all-cause and cardiovascular IMRs were significantly lower in our series with respect to the Leiden Early Arthritis Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than in any other European cohorts. Conclusion: We confirm that the mortality rate is lower in our Italian RA cohort with respect to other European cohorts. Whether the low prevalence of anti-CarP Ab might be responsible for this result awaits to be furtherly investigated.
Arthritis research & therapy, 2015
The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic in...