Changes in the composition of certain immune system cells may be associated with relapses in multiple sclerosis (MS) patients being treated with Gilenya (fingolimod), according to a study published in the journal Scientific Reports.
The study, “Altered T Cell Phenotypes Associated With Clinical Relapse Of Multiple Sclerosis Patients Receiving Fingolimod Therapy,” was conducted by researchers in Japan.
In MS patients, immune cells called T-cells penetrate the brain and react against the myelin coating that protects and supports neurons. But before this autoimmune response occurs, T-cells undergo certain migratory steps.
Gilenya acts by inhibiting the movement of T-cells from secondary lymphoid organs, and by decreasing the number of central memory T-cells (TCM), which are mediators of inflammation. Clinical trials have demonstrated its effectiveness in reducing clinical relapses.
But certain studies suggest that Gilenya does not lower the number of TCM cells in the peripheral blood (blood that flows to the extremities) sufficiently, and the medication is associated with relapses during treatment. But whether these relapses are caused by peripheral blood levels of TCM cells or other mechanisms is still unclear.
Researchers analyzed the T-cells present in blood samples from patients undergoing Gilenya therapy, in remission and at relapse, and compared their findings with Gilenya-untreated MS patients and healthy subjects.
A total of 33 patients with relapsing-remitting MS and 10 controls were included in the study. Gilenya was administered to 16 patients (F-MS group). Of these, 11 did not experience relapses (relapse-free F-MS), and five did (relapse-experienced F-MS). Patients considered in remission were clinically stable for more than 30 days, while relapse was considered the period within 14 days after the start of a flare, with neurological episodes lasting more than 24 hours.
The analysis indicated that T-cell composition was altered in patients under Gilenya treatment, changes not found in the other groups, and that these changes increased markedly during relapse. In particular, patients receiving Gilenya at relapse had increased levels of CD56+-expressing T cells, which have been associated with MS pathology.
“The first striking finding in this study is that the frequency of CD56+ T cells increased in [Gilenya]-treated patients, which was not observed in patients [receiving other therapies],” the authors wrote. “Notably, these T cell populations appeared to be related to relapse under [Gilenya] therapy, because they further increased during relapse.”
“In contrast, TCM [cells] rather decreased in relapsed F-MS patients more than those in relapse-free F-MS patients, indicating that an insufficient reduction in TCM in the peripheral blood cannot fully explain relapse on [Gilenya] in this study.”
A clinically important finding, they added, was that “the CD56+ population was increased 6 months before relapse in one patient. Relapse-experienced F-MS patients retained a high frequency of CD56+ T cells even during remission. Our data has raised a possibility that the frequency of CD56+ T cells is a useful biomarker for predicting relapses, although further confirmation of this measure is required.”
Based on the results, the team concluded, “Fingolimod [Gilenya] therapy may place MS patients in different immune situations although fingolimod itself does not necessarily exert a direct effect on upregulation of CD56 on T cells.” An increase in the frequency of T-cells expressing CD56+, particularly during relapses, seems to exacerbate the pathology of MS in patients receiving Gilenya.
Further studies are required to understand the role of CD56+ T-cells in MS relapses in people under Gilenya treatment.
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