Induction of apoptosis in CD4(+) T-cells is linked with optimal treatment response in patients with relapsing-remitting multiple sclerosis treated with Glatiramer acetate.

ABSTRACT

BACKGROUND: Induction of T-cell apoptosis constitutes a mechanism of action for Glatiramer Acetate (GA). We investigated whether activation of apoptotic T-cell death may be indicative of optimal treatment response in patients with relapsing-remitting Multiple Sclerosis (RRMS), with respect to radiological activity. METHODS: We studied apoptotic markers on blood T-cells of forty patients with RRMS, 19 patients under GA and 21 patients under interferon-ß (IFNß), by flow cytometry. Patients were relapse-free and were further classified into optimal and sub-optimal responders based on radiological activity. Eighteen patients (8 patients under GA and 10 patients under IFNß were additionally evaluated at a 12-month follow-up and were relapse- and radiological activity-free. For these patients, apoptosis was also evaluated by molecular techniques. RESULTS: At inclusion, optimal responders to GA exhibited increased (23.6 ±â€¯1.976) relative % frequency of CD4(+)AnnexinV(+)7AAD(-) T-cells, compared to sub-optimal responders (14.478 ±â€¯1.204, p = 0.001). Similarly, relative % frequency of caspase-3(+) T-cells was 1.517 ±â€¯0.436 versus 0.45 ±â€¯0.149 (p = 0.041), respectively. Anti-apoptotic molecule bcl-2 showed an inverse pattern 4.532 ±â€¯1.321 versus 13.094 ±â€¯3.987, p = 0.044, respectively. These differences were not evident for IFNß-treated patients. CONCLUSIONS: T-cell apoptotic markers may be applied as a biomarker useful in evaluating optimal treatment response under GA, thus allowing for personalized treatment decisions.