Association of and gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population.

Introduction: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Although RA is chiefly associated with HLA class II, nevertheless some HLA class I associations have also been observed. These molecules present antigenic peptides to CD8+ T lymphocytes and natural killer cells. HLA-I molecules bind their peptide cargo (8-10 amino acids long) in the endoplasmic reticulum. Peptides longer than 10 amino acids are trimmed by the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 to fit the peptide binding groove of the HLA-I molecule. Here, we investigated the possible association of and polymorphisms with RA, and also any possible correlation between serum levels of the ERAP2 protein with disease severity.

Methods: We used Real-Time PCR to genotype and and ELISA test to detect protein.

Results: We found significant associations of rs30187, rs27044, and rs26618, as well as rs2248374, with susceptibility to RA. rs26653 and ERAP2 rs2248374 were also associated with the Disease Activity Score (DAS28), and some polymorphisms were also associated with anti-citrullinated protein or anti-mutated citrullinated vimentin antibodies. RA patients secreted higher concentrations of ERAP2 than controls. Patients with mild disease activity (DAS28 < 3.2) released a concentration of ERAP2 four times lower than that of patients with severe disease activity (DAS28 > 5.1). We detected a higher level of in rheumatoid factor (RF)-positive patients than in RF-negative patients. concentration above 5.85 ng/mL indicated a severe phase of RA.

Conclusions: Some and polymorphisms seem to be related to susceptibility to RA or the severity of the disease. The ERAP2 protein tested in serum could be a valuable biomarker of RA severity.