Anti-hnRNP B1 (RA33) Autoantibodies Are Associated with the Clinical Phenotype in Russian Patients with Rheumatoid Arthritis and Systemic Sclerosis

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic targets in systemic autoimmune rheumatic diseases (SARD). Loss of tolerance to the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1 and B2 has been the interest of rheumatologists. A novel ELISA for the detection of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence thereof in 397 patients with SARD, including patients with rheumatoid arthritis (RA), spondyloarthropathy (SPA), juvenile chronic arthritis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome (SS), in comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%; P < 0.001). In particular, anti-hnRNP B1 were found more frequently in the disease cohorts than in the controls and were present in 24/165 (14.5%) patients with RA, 6/58 (10.3%) SPA, 11/65 (16.9%) SSc, and 4/50 (8.0%) SLE. In RA patients, anti-hnRNP B1 autoantibodies correlated significantly with C-reactive protein levels and erythrocyte sedimentation rate, while in patients with SSc it was associated with features of arterial wall stiffness and presence of hypertension. Anti-hnRNP B1 autoantibodies occur in SARD and seem to be correlated with distinct clinical characteristics in patients with RA and SSc.

Antibodies to native and citrullinated RA33 (hnRNP A2/B1) challenge citrullination as the inciting principle underlying loss of tolerance in rheumatoid arthritis

“…In accordance with a previous study,25 we found that anti-RA33 antibodies were more frequently observed in patients with shorter disease duration (16.4% of patients <4 years after disease onset), and progressively lower in patients later in their disease course (6.3% of patients at >18 years after disease onset). This trend was inversely observed for anti-citRA33 antibodies, which were more prevalent in patients with longer standing RA (56.3% at >18 years) (figure 4D).…”

“…In patients with RA, anti-RA33 antibodies have been shown to target hnRNP A2/B1 as an unmodified protein,6 25 which may suggest that RA33 is a distinct antibody system in the aetiopathogenesis of RA, presumably driven by mechanisms independent of citrullination. Our findings challenge this interpretation by identifying RA33 as citrullinated synovial protein that is targeted by ACPAs.…”

High frequency ultrasonography of the hand versus anti-RA33 evaluation in early rheumatoid arthritis - a pilot study

“…Besides anti-CCP antibodies, present very early in the course of the disease, anti-RA33 antibodies can constitute an additional marker, not only for improving diagnosis, but also for assessing the prognosis and therapeutic response [5,27,28].…”

Autoantibody and metalloproteinase activity in early arthritis

“…They react with pre-mRNA and are involved in cellular processes such as DNA repair and chromatin remodeling. In early RA, they are found in 14% of cases [41]. In patients diagnosed with RA, they have high sensitivity, up to 98%, but low specificity (20%), according to literature reports [42].…”