The proportion of peripheral regulatory T cells in patients with Multiple Sclerosis: A meta-analysis

Accumulating evidence indicates that regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance. And dysfunction or deficiency of Tregs is thought to be involved in the pathogenesis of Multiple Sclerosis (MS). Nevertheless, previous studies reporting Tregs in patients were controversial due to the different markers adopted to identify Tregs. To clarify the status of Tregs in the pathogenesis of MS patients, we did a meta-analysis of the results published previously to assess the proportion of Tregs in peripheral blood (PB) in patients with MS.

We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in MS patients. Our main endpoints were the proportion of Tregs among CD4⁺ T cells in PB defined by different markers. We assessed pooled data by using a random-effects model. Our meta-analysis had been registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017064906).

Of 885 identified studies, a total 16 studies were selected in our analysis. There was no significant difference between MS patients and control subjects in Tregs identified by all Tregs definition methods [-0.07, (-0.46, 0.31, p = 0.706)] and Tregs defined by "CD4⁺ CD25⁺" [0.24, (-0.18, 0.65), p = 0.263]. Compared with control subjects, MS patients had a lower proportion of Tregs defined by "CD4⁺ CD25⁺ FOXP3⁺" [-0.75, (-0.46,0.31), p = 0.001].

Under random effect model of meta-analysis, the data showed that the results of Tregs in MS were different according to the definition method; and the proportion of Tregs defined by "CD4⁺ CD25⁺ FOXP3⁺" was decreased in MS. That result demonstrates that FOXP3 may be a vital definition of Tregs, and Tregs defined by stricter definition methods should be involved in the pathogenic mechanisms of MS.