Abatacept suppresses the telomerase activity of lymphocytes in patients with rheumatoid arthritis.

Abstract

Telomere is a component of chromosomes that protects their ends from various stresses. The telomeres shorten during cell division, and their length is maintained by telomerase. The telomerase activity of lymphocytes was shown to be upregulated on lymphocyte activation, and abatacept was found to suppress the activation of T lymphocytes involved in pathogenesis of rheumatoid arthritis. Therefore, we investigated the effect of abatacept on lymphocyte telomerase activity in patients with rheumatoid arthritis. This study included 11 patients diagnosed with rheumatoid arthritis based on American College of Rheumatology 2010 criteria, who received abatacept treatment from August 2012 to August 2013. We collected their clinical data and obtained peripheral blood samples before starting abatacept, and 1, 3, 6, and 12months after treatment. Peripheral blood mononuclear cells were extracted using Ficoll density gradient centrifugation, and T and B lymphocytes were sorted by magnetic beads. The telomerase activity of lymphocytes was determined using the telomeric repeat amplification protocol. The telomerase activity of T lymphocytes declined from 0.357 to 0.161 (P<0.01) at 12months after abatacept treatment, and that of B lymphocytes declined from 0.554 to 0.202 (P<0.01). The telomerase activity of B lymphocytes, but not that of T lymphocytes, was also significantly downregulated 1month after treatment. Abatacept suppressed the telomerase activity of both T and B lymphocytes, although that of B lymphocytes was downregulated before T lymphocytes. These findings imply that the clinical efficacy of abatacept during the early phase depends on the suppression of B lymphocytes.