Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Inflammatory cytokines and cell-mediated immunity function of mainly lymphocytes are complicatedly involved in disease onset of rheumatoid arthritis (RA). Recently, together with biologicals such as tumor necrosis factor-alpha (TNF-α) inhibitor and interleukin-6 (IL-6) inhibitor, which block the signal transduction into cells via cytokine, T-cell costimulatory modulator (Abatacept, ABT), which uses mechanism of cytotoxic T-Lymphocyte Antigen 4 (CTLA4) as cell auxiliary signal molecule that frequently develops on the membrane with activated T lymphocytes, has been used to treat RA. In this study, we examined the impact of treatment with ABT on a subfraction of natural killer (NK) cells (CD57) in peripheral blood.
The subjects were 32 RA patients treated with ABT (6 men and 26 women; aged 39 to 81 years, mean 62). The duration of disease was 10.0 ± 7.9 years (1 to 30 years). Eight, 14, and 10 patients had stage II, III, and IV RA, respectively. Of these, 16 biological-naïve patients and 16 patients who had received other biologicals were included. Blood samples were collected before each administration at 0 week (before treatment), and at 4, 12, 24, and 52 weeks. The changes in CD8+/CD57, CD8+/CD11b+, and CD4+/CD25+, which were demonstrated by double-staining with fluorescein isothiocyanate and phycoerythrin, were assessed by flow cytometry.
Lymphocyte subset (%) according to the stage at the induction of ABT was as follows (mean ± SE). For CD8+/CD11b+, 13.2 ± 1.8, 15.7 ± 2.2, and 22.0 ± 3.1 in patients with stage II, III, and IV, respectively. For CD8+/CD57+, 12.9 ± 1.9, 18.0 ± 3.1, and 19.5 ± 3.9 in patients with stage II, III, and IV, respectively; higher values were observed in patients with advanced stage, although there was no statistically significant difference among the stages. For CD8+/CD57+, 26.9 ± 2.9, 25.4 ± 2.5, and 26.3 ± 3.1 in the patients with stage II, III, and IV, respectively; there was no substantial difference among the stages. The change between the value before treatment with ABT and that at the 52nd week was as follows: for CD8+/CD11b+, 16.7 ± 1.6 and 12.1 ± 1.1, p < 0.02; for CD8+/CD57+, 16.9 ± 1.9 and 10.2 ± 1.1, p < 0.004; both values were significantly decreased after 52 weeks. For CD4+/CD25+, 26.4 ± 1.6 and 28.1 ± 1.6; although the value increased at 52 week, there was no significant difference. However, CD4+/CD25+high cells were decreased gradually until the 52nd week in the biological-naïve patients, but were increased from the 12th week after administration in patients receiving ABT switched from other biologicals.
In this study, CD8+/CD57 and CD8+/CD11b+ before treatment tended to be higher as the stage of RA advanced. This tendency was maintained after 52 weeks. The values were decreased for 52 weeks in each patient. The proportion of D8+/CD57 and CD8+/CD11b may reflect the therapeutic effect of ABT. It is not known whether the changes in CD4+/CD25+high cells observed in the patients receiving ABT switched from other biologicals indicated cell activation or showed the dynamics of auto-regulatory cells such as regulatory T cells.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-study-of-natural-killer-cell-subfractions-in-abatacept-therapy-for-rheumatoid-arthritis/