Cyclic citrullinated peptide

We describe the study of a novel aptamer-based candidate for treatment of seropositive rheumatoid arthritis. The candidate is a nanoparticle-formulated cyclic citrullinated peptide aptamer, which targets autoantibodies and/or the immune reactions leading to antibody production. Due to its specificity, the peptide aptamer nanoparticles might not interfere with normal immune functions as seen with other disease-modifying antirheumatic drugs. Over a 3-week course of treatment, joint swelling and arthritis score in collagen-induced rats were significantly decreased compared with animals treated with phosphate-buffered saline, unloaded nanoparticles, or nanoparticles with a noncitrullinated control peptide. The reduction in joint swelling was associated with decreased anticitrullinated peptide autoantibody levels in the blood. Treatment with aptamer nanoparticles also increased interleukin-10 levels. The effect seen with the proposed treatment candidate could be mediated by upregulation of anti-inflammatory mediators and decreased levels of anticitrullinated peptide antibodies.

Rationale: Anti-CCP antibodies are detectable not only in rheumatoid arthritis (RA), but also in psoriatic arthritis (PsA). It is possible those anti-CCP antibodies are associated with features of PsA and that these auto-antibodies are useful in distinguishing PsA from RA. Objective: to evaluate the prevalence and the associations of anti-CCP antibodies in PsA patients; to evaluate the usefulness of anti-CCP antibodies in distinguishing PsA from RA. Methods and results: The inquiry was designed as a cross-sectional study of 41 PsA patients, 139 RA patients and 147 normal subjects, which recorded demographic data, disease activity and serology: rheumatoid factor (RF), anti-CCP antibodies. Five PsA patients (12.2%) were anti-CCP positive. Compared to anti-CCP negative PsA patients, anti-CCP positive PsA patients had a more frequently a polyarticular disease pattern (p = 0.005), they were more frequently treated with biologics (p = 0.015) and less frequently with classic disease-modifying drugs (p < 0.001). An optimal positive cutoff value for anti-CCP titer was determined (11.6 U/mL), over which it is highly probable that a known PsA patient actually has RA and psoriasis. Discussion: The more aggressive the disease of anti-CCP positive PsA patients indicates the need of a more intensive management regarding anti-rheumatic treatment and follow-up. Anti-CCP antibodies can be a useful tool in differentiating PsA from RA, especially in RA-like forms of PsA, which present no elements pertaining to spondyloarthropathies.

Objectives: We assessed the ability of anti-cyclic citrullinated peptide (CCP) tests to diagnose rheumatoid arthritis (RA), comparing the effect of manufacturer assay type, study design (single- and two-gated) and duration of disease (early vs. established). Methods: We searched seven databases for relevant diagnostic studies containing data on CCP tests in known or suspected RA patients. We used a bivariate model to produce summary estimates for test sensitivity, specificity, and positive and negative likelihood ratios. Summary Receiver Operating Characteristic (sROC) curves were derived to compare early versus established RA. Results: 83 studies were identified and included. For individual manufacturer tests there was considerable variation in both pooled sensitivity (range 67-83%) and specificity (range 90-96%) estimates. This heterogeneity was also observed when grouping studies into two-gated and single-gated designs. Study design and disease duration impacted on sensitivity, with single-gated study designs and early RA patients resulting in lower estimates than two-gated and established disease, respectively. Conclusions: This review highlights the large number of CCP tests that are now commercially available and the considerable variation in their diagnostic performance. This variation, although partly influenced in this analysis by the study design (single-gated vs. two-gated), seems to have different levels of impact depending on the manufacturers. The Thermo Fisher Scientific EliA and Inova Diagnostics Quanta Lite (CCP2) tests showed the least between-study variation in sensitivity and specificity suggesting they have the most consistent diagnostic performance overall.