Induction of apoptosis in CD4(+) T-cells is linked with optimal treatment response in patients with relapsing-remitting multiple sclerosis treated with Glatiramer acetate.
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-β (IFNβ), 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 IFNβ 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 ± 1.976) relative % frequency of CD4(+)AnnexinV(+)7AAD(-) T-cells, compared to sub-optimal responders (14.478 ± 1.204, p = 0.001). Similarly, relative % frequency of caspase-3(+) T-cells was 1.517 ± 0.436 versus 0.45 ± 0.149 (p = 0.041), respectively. Anti-apoptotic molecule bcl-2 showed an inverse pattern 4.532 ± 1.321 versus 13.094 ± 3.987, p = 0.044, respectively. These differences were not evident for IFNβ-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.
['Boziki|Marina|M|', 'Lagoudaki|Roza|R|', 'Melo|Pamela|P|', 'Kanidou|Foteini|F|', 'Bakirtzis|Christos|C|', 'Nikolaidis|Ioannis|I|', 'Grigoriadou|Eleni|E|', 'Afrantou|Theodora|T|', 'Tatsi|Theano|T|', 'Matsi|Stavroula|S|', 'Grigoriadis|Nikolaos|N|']
D000328:Adult D017209:Apoptosis D015496:CD4-Positive T-Lymphocytes D005260:Female D005434:Flow Cytometry D005500:Follow-Up Studies D000068717:Glatiramer Acetate D006801:Humans D007166:Immunosuppressive Agents D016899:Interferon-beta D008297:Male D008875:Middle Aged D020529:Multiple Sclerosis, Relapsing-Remitting D016896:Treatment Outcome
Apoptosis Multiple sclerosis Glatiramer acetate Radiological activity Interferon-β Disease modifying treatment