FOXP3rs3761548 gene variant and interleukin-35 serum levels as biomarkers in patients with multiple sclerosis.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). Aberrant expression of transcription factor forkhead box P3 (FoxP3) has been suggested to underlie different immunological disorders as FOXP3 expression is essential for T regulatory cells (Tregs) to maintain their suppressive and anti-inflammatory functions and exert immunologic self-tolerance. Interleukin-35 (IL-35) is an important immunosuppressive cytokine that is produced mainly by CD4+ FOXP3+ Tregs. To assess the possible role of the FOXP3 rs3761548 (C/A) single-nucleotide variation (SNV) in relapsing-remitting multiple sclerosis (RRMS). Also, measurement of the serum IL-35 concentration and study its relation to different genotypes and the degree of disease-related disability. A total of 100 RRMS patients and 90 healthy control subjects were subjected to genotyping for the FOXP3 (rs3761548) variant by TaqMan real-time PCR, and measurement of the IL-35 level in their sera by Elisa. The frequencies of the AA genotype and A allele were significantly higher in the MS patients than in the healthy controls (P=0.008, OR=2.53, 95% CI=1.27-5.04; P=0.001, OR=1.98, 95% CI=1.31-3.00, respectively). There was a significant association between FOXP3 rs3761548 variant and female MS patients. The serum IL-35 level was significantly higher in MS patients (1372 [575-2192] pg/mL) compared to healthy controls (604 [454-696] pg/mL) (P<0.0001). No significant differences were found between the different FOXP3 genotypes and EDSS score (P=0.730). The FOXP3rs3761548 gene variant may influence the genetic susceptibility to MS rather than affecting its course, severity or progression. The serum IL-35 level might have a role in the development of the disease, however its role in disease-related disability is questionable.