Role of blister fluid soluble HLA-E In SJS/TEN

Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening hypersensitivity reactions to medications characterized by keratinocyte apoptosis, the formation of subepidermal blisters, and skin detachment. Cytotoxic lymphocytes including CTLs and NK cells seem to be the main effectors of keratinocyte killing. Natural killer cytotoxic activity is regulated through the balance of activating and inhibitory signals delivered by innate receptors, some of which recognize HLA class I antigens. Among them, inhibitory CD94/ NKG2A and activating CD94/NKG2C receptors are specific for the non-classical HLA class Ib molecule HLA-E, and are expressed not only in NK cells but also in subsets of T lymphocytes. We have previously reported that the activating receptor CD94/NKG2C is overexpressed in lymphocytes from SJS/TEN patients resulting in net activation and lysis of HLA-E+ targets. Moreover, HLA-E was found to be overexpressed in affected skin, and in agreement with previous reports showing soluble HLA-E (sHLA-E) released in response to cell activation, we found sHLA-E in blister fluids from SJS/TEN patients.