Background Cytotoxic T-lymphocyte antigen (CTLA) 4 is a molecule that suppresses T-cell activation and is expressed on the surface of regulatory T cells. Abatacept (ABT), a fusion protein fused to CTLA-4, is used in the treatment of rheumatoid arthritis (RA).
Objectives The purpose of this study was to analyze the effect of ABT therapy on the CD4+/CD25+high fraction, which is thought to include regulatory T cells in the peripheral lymphocyte fractions of RA patients, and to elucidate whether this can be correlated to therapeutic outcome.
Methods The subjects were 32 RA patients who were currently being treated with ABT therapy. The patients' background characteristics were as follows: age ranging from 39 to 81 years (mean: 62±12 years.), stage II disease in 8 patients, stage III disease in 14 patients, and stage IV disease in 10 patients. Sixteen patients were switched from other biological preparations, and 16 patients were ABT naive. Changes in CD4+/CD25+ and CD4+/CD25+high expression levels in blood tests prior to ABT administration were determined by using fluorescein isothiocyanate and phycoerythrin double stain, and measured by using flow cytometry in 5 points: 0 (prior to first ABT administration), 4, 12, 24, and 52 weeks.
Results CD4+/CD25+ (%) showed a slight elevation at week 12 with subsequent decline followed by a slight elevation at week 52, although no significant differences were observed. Measured values at weeks 0, 4, 12, 24, and 52 were 26.4±1.6, 26.7±1.5, 28.9±1.7, 26.8±1.6, and 28.1±1.6, respectively. No significant differences in these values were observed between the switched and naive groups. However, our analysis of the CD4+/CD25+high distribution revealed that in the naive group, an interim decline occurred at week 52, but significant elevations were observed in the switched group starting at week 12. Analysis of the responders (10 cases) and non-responders (6 cases) to ABT in the switched group indicated that the responders showed significant declines in CD4+/CD25+high levels between weeks 12 and 52, as did the cases in the naive group. However, the non-responders showed significant elevations in this fraction from initial ABT administration until week 52.
Conclusions Based on the fact that CTLA-4 is expressed on the surface of regulatory T cells, considering that ABT is a fusion protein that fuses CTLA-4 and immunoglobulin and regulatory T cells are present in the CD4+/CD25+high fraction, as well as the results of this study, we believe that in cases in which satisfactory therapeutic effects were obtained through the use of ABT, the expression level of regulatory T cells declined. However, patients who were refractory to ABT therapy experienced CTLA-4 deficiency, which we believe caused regulatory T cells to be expressed. Based on these results, changes in the CD4+/CD25+high fraction can be used to measure the therapeutic efficacy for RA from the perspective of CTLA-4.
Disclosure of Interest None declared
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