Forkhead Box P3 (Foxp3) serum level and Foxp3 Gene-Promoter polymorphisms in Egyptian rheumatoid arthritis patients: A case-control study

Regulatory T (Treg) cells are the chief player in induction of autotolerance and the transcription factor, Forkhead Box P3 (Foxp3), is the master regulator of their development and function. Polymorphisms in Foxp3 locus affect Foxp3 expression and can influence Treg cell function. This study aimed to determine the frequency of -3279C/A and -924A/G polymorphisms in the promoter region of the Foxp3 gene in Egyptian rheumatoid arthritis (RA) patients in comparison to apparently healthy controls, to test their association with Foxp3 serum levels as well as with patients’ clinical and laboratory features. Also, to evaluate Foxp3 serum level as a putative measure of Foxp3+ Treg cells-mediated immune regulation and disease activity. A total of 136 subjects (68 RA patients and 68 controls) were studied for determining the frequency of both -3279 C/A and -924 A/G polymorphisms in the Foxp3 promoter region by PCR-RFLP and measuring their Foxp3 protein serum levels by ELISA. Our results indicated that; -3279 Foxp3 CA and AA genotypes were significantly higher in patients than controls (OR (95% CI) = 2.86 (1.31-6.26) and 2.79 (1.11-7.07), P= 0.008 and p = 0.03, respectively). Similarly, -924 AG genotype was significantly higher in patients than controls (OR (95% CI) = 2.92 (1.35-6.34); P=0.006). A significantly higher risk of RA was associated with the Foxp3 polymorphic variants -3279 A and -924 G. There was a statistically significant elevation in Foxp3 serum levels among patients, which was positively correlated to disease activity score and disease grade. In conclusion, Foxp3 polymorphisms influenced the risk of developing RA, but did not influence disease severity or activity. Serum level of Foxp3 is not a reliable indicator of Treg-mediated immune regulation in RA patients.