Endogenous retroviruses are known to represent 8% of the Human genome. HERV-W family retains elements expressing an envelope protein (Env), which activates a pro-inflammatory and autoimmune cascade through interaction with Toll-Like receptor 4 (TLR4). This Env protein was evidenced in brain lesions, sera and circulating mononuclear cells of patients with Multiple Sclerosis (MS)1. Thus, all the background science from the past two decades that has brought independent confirmations and reproductions of an involvement of HERV-W in MS 2 convinced us to further study its association with other “autoimmune diseases”. If no association was found when testing series of patients with rheumatoid arthritis3 or systemic lupus1, about one-third of sera from patients with T1D revealed positive for the HERV-W Envelope antigen. We therefore further explored whether this immunopathogenic endogenous protein could be expressed in pancreas from T1D versus controls, which revealed positive in about 40% of first pilot series, and are now preparing to extend these analyses to larger number of serum, PBMC and pancreas samples. In parallel, we are developing an HERV-W-Env induce mouse model of diabetes for pre-clinical studies with an anti-Env neutralizing humanized antibody.
