Increased levels of sCD40L have been reported in pSS [4, 5]. As compared with controls, patients with SLE showed increased proportion of CD40L-expressing CD4+ T cells after T cell mitogenic stimulation or PMA and ionomycin activation, which suggests defective regulation of CD40L expression in SLE [13, 14]. The mechanisms leading to such CD40L superinduction of mitogenic stimulation in SLE are still poorly understood. In this study, induced membrane-bound CD40L of CD4+ T cell was higher in patients with pSS than in controls,

as previously reported in SLE. This finding was not due to a difference in DNA methylation patterns of key regulatory regions of Selleck IDH inhibitor CD40L among patients with pSS as confirmed by 2 different methods: pyrosequencing and functional analyses with a demethylating agent. Epigenetic Ibrutinib mouse deregulation of CD40L was proposed to explain CD40L overexpression in SLE [2] and SSc [3]. In these latter studies, the mean methylation level of the promoter differed between patients and controls possibly because of different CD40L mRNA levels between patients and controls. The regulatory regions of the promoter we analysed were identical to those assessed in the SLE and SSc studies, which suggests different mechanisms of CD40L membrane overexpression in pSS and SSc or SLE. Further,

using a genome-wide DNA methylome approach that is currently been undertaken in the laboratory, we studied 6 probes within the CD40L gene and 4 in the proximal promoter region and found no difference in methylation pattern in cell sorted T cells between patients and controls (data not shown) in any of these 10 analysed CpGs. An alternative epigenetic deregulation through Glycogen branching enzyme microRNA (miRNA) could

be involved in the increased CD40L level in pSS. MiRNA are small non-coding RNAs (fragments of single-stranded RNA) that regulate gene expression via mRNA degradation or, more rarely, translational repression. MiR-146a expression was found repressed in SLE and negatively associated with clinical disease activity and IFN values [15]. As miR-146a targets CD40L, down-regulation of miR-146a could lead to an overexpression of the CD40L protein. In this hypothesis, we could also expect an overexpression of CD40L mRNA as it has been shown in the literature [16]. Thus, we can hypothesize either an inhibitory action of miR-146a on CD40L translation without any decrease in the target CD40L mRNA or a down-regulation of membrane-bound CD40L due to differences in its intracellular trafficking between patients with pSS and controls. Our study demonstrates an overexpression of inducible membrane-bound CD40L on CD4+ T cells in patients with pSS but was not related to epigenetic deregulation by demethylation patterns of the regulatory regions of CD40L, as previously reported in SLE. Such overexpression suggests that CD40L could be an interesting target in autoimmune disease. The authors declare no competing interests.