Association of TNFRSF1B Promoter Polymorphisms with Human Disease: Further Studies Examining T-Regulatory Cells Are Required

The TNFR2 receptor is expressed by highly active regulatory T cells, and thus constitutes an important therapeutic target for the treatment of autoimmune disease and cancer. Disease susceptibility as well as the potential response to therapies directed at TNFR2 could be significantly impacted by genetic variation in the promoter of the TNFRSF1B gene that codes for the TNFR2 protein. To date, only a few studies have examined the association of TNFRSF1B promoter variation with disease, and the potential impact on T-regulatory cell (Treg) number and function has not been examined. We propose that copy number variation of a key transcription factor binding site has a significant effect on TNFRSF1B promoter activity, and should be considered in studies of disease susceptibility and especially with regard to variation in the level of TNFR2 expression on Tregs.