Untitled

Abstract

Heterogeneity and multifactoriality complicate diagnostics and our understanding of pathogenesis of rheumatoid arthritis (RA). The only accepted serologic parameter (rheumatoid factor [RF]) is not disease specific, nor are any of several novel RA autoantibodies. We aimed at identifying profiles instead of individual autoreactivities allowing for unambiguous prediction of RA. Selected RA autoantigens were tested by ELISA (RF and anti-cyclic citrullinated peptide [anti-CCP]) or Western blot (heavy-chain-binding protein [BiP], heterogeneous ribonucleoprotein particle A2 [RA33/ hnRNP A2], calpastatin and calreticulin). Antibody reactivities were assayed from serum samples of 149 RA patients and 132 patients with other rheumatic diseases and from synovial fluids (SF) (58 RA, 65 non-RA). No single autoreactivity was sufficient for unambiguous prediction of RA. Frequencies of multiparameter profiles consisting of 3, 4, 5 and 6 autoreactivites were determined. Fifteen six-parameter serum profiles were exclusively expressed in RA patients, representing a cumulative sensitivity of 59%. Twelve SF profiles were exclusively expressed in 64% of RA patients. The self-learning classification algorithm CLASSIF1 was capable of accurately predicting RA when these profiles were present. Data profile analysis of RF/CCP/BiP/calpastatin/calreticulin/RA33 provided specific discrimination of 64% of RA. Most importantly, RA specific profiles were observed in 64% of patients with early disease (<12 months). For the first time, the accurate prediction of the class RA has been achieved by the use of multiparametric autoreactivity profiles. Because of early expression in disease, these profiles make it possible to start a disease-modifying therapy long before irreversible bone and joint destruction may develop. Additional RA-specific profiles are required to cover the entire group of RA patients. 2 Investigation of the reactivity patterns of antifilaggrin antibodies in sera and synovial fluids from patients with rheumatoid arthritis using citrullinated synthetic peptides

Systemic Bone Density at Disease Onset Is Associated With Joint Erosion Progression in Early Naive to Treatment Rheumatoid Arthritis: A Prospective 12-Month Follow-Up Open-Label Study

“…In our study, we enrolled consecutive ERA patients at disease onset without previous exposure to conventional or biological DMARDs in whom plasma levels of bone-derived biomarkers were assessed, finding that women older than 50 years old have higher DKK1 plasma levels than men older than 50 years old and higher RANKL plasma levels than men younger than 50 years old. Moreover, we found that in ERA patients, OPG plasma levels directly correlated with age at disease onset regardless of sex, as was previously demonstrated in healthy subjects (31) as well as in systemic diseases characterized by bone loss (32). This might reflect a compensatory self-defense mechanism against age-related osteoporosis.…”