Microparticles and autophagy: a new frontier in the understanding of atherosclerosis in rheumatoid arthritis.

Microparticles (MPs) are small membrane vesicles released by many cell types under physiological and pathological conditions. In the last years, these particles were considered as inert cell debris, but recently many studies have demonstrated they could have a role in intercellular communication. Increased levels of MPs have been reported in various pathological conditions including infections, malignancies, and autoimmune diseases, such as rheumatoid arthritis (RA). RA is an autoimmune systemic inflammatory disease characterized by chronic synovial inflammation, resulting in cartilage and bone damage with accelerated atherosclerosis increasing mortality. According to the literature data, also MPs could have a role in endothelial dysfunction, contributing to atherosclerosis in RA patients. Moreover many researchers have shown that a dysregulated autophagy seems to be involved in endothelial dysfunction. Autophagy is a reparative process by which cytoplasmic components are sequestered in double-membrane vesicles and degraded on fusion with lysosomal compartments. It has been shown in many works that basal autophagy is essential to proper vascular function. Taking into account these considerations, we hypothesized that in RA patients MPs could contribute to atherosclerosis process by dysregulation of endothelial autophagy process.

Anti-carbamylated protein antibodies in systemic lupus erythematosus patients with articular involvement.

Objective Several studies have evaluated the prevalence of rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA) in systemic lupus erythematosus (SLE) patients but no data are available on the anti-carbamylated proteins (anti-CarP), a new biomarker for rheumatoid arthritis (RA). We evaluated the anti-CarP prevalence in SLE patients with joint involvement and the associations with different phenotypes. Methods Seventy-eight SLE patients with joint involvement were enrolled (F/M 73/5; mean ± SD age 47.6 ± 11.2 years; mean ± SD disease duration 214.3 ± 115.6 months). As control groups, we evaluated SLE patients without joint manifestations ( N = 15), RA ( N = 78) and healthy individuals (HS, N = 98). Anti-CarP were assessed by home-made ELISA in all patients and controls, RF and ACPA in SLE patients with joint involvement (commercial ELISA kit). Results The prevalence of anti-CarP in SLE patients with joint involvement was similar to RA ( p = NS) and significantly higher compared with SLE without joint involvement and HS ( p < 0.0001, p < 0.0001, respectively). Four patients were positive for all three antibodies: seventy-five percent of these showed Jaccoud arthropathy. Fourty-five percent of ACPA-ve/RF-ve patients were anti-CarP + ve. Conclusions The evaluation of anti-CarP in SLE joint involvement demonstrated a prevalence of almost 50%, similar to RA and significantly higher than SLE without joint involvement and HS.

Anti-carbamylated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients: lack of correlation with anti-cyclic citrullinated protein antibodies and rheumatoid factor.

OBJECTIVES: To investigate the prevalence of anti-carbamylated protein antibodies (anti-CarP) in the healthy first-degree relatives (HFDRs) of patients with rheumatoid arthritis (RA). METHODS: We enrolled 141 HFDRs of 63 patients with RA diagnosed accordingly to the 2010 ACR/EULAR criteria. Fifty-six normal healthy subjects (NHS), sex- and age-matched, served as controls. Anti-CarP IgG, anti-cyclic citrullinated peptide antibody (anti-CCP) IgG and rheumatoid factors (RF) isotypes (IgG, IgA, IgM) were assessed by solid-phase ELISA. RESULTS: Anti-CarP were detectable in 13 HFDRs (9.2%), anti-CCP in 9 (6.3%), IgG-RF in 10 (7%), IgA-RF in 17 (12%), and IgM-RF in 13 (9.2%) HFDRs. Twenty-nine (46%) RA patients were positive for anti-CarP, 31 (49.2%) for anti-CCP, and 34 (53.9%) for RF. One NHS (1.7%) resulted positive for anti-CarP, none for anti-CCP and RF. Anti-CarP showed significantly higher serum levels in RA and HFDRs than in NHS (p<0.0001 and p=0.0012, respectively). A significant correlation between anti-CCP and RF were found among RA patients (p=0.0002), whereas no correlations were reported between autoantibodies tested in the HFDRs. CONCLUSIONS: Anti-CarP can be found in the sera of HFDRs of RA patients and their prevalence is significantly higher than in NHS. No correlation of anti-CarP with anti-CCP and RF antibodies in RA HFDRs was found.