The role of KIR2DS1 in multiple sclerosis - KIR in Portuguese MS patients

•NK cells contribute to effector and regulatory functions of innate immune system.•The role of NK cells in the pathogenesis of MS is still unclear.•NK cells interact with HLA class I antigens through KIR receptors.•We studied the influence of KIR genes on MS susceptibility in Portuguese patients.•The activating KIR2DS1 receptor seems to confer protection against MS.

Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. We observed a negative association between the activating KIR2DS1 gene and MS (adjusted OR = 0.450, p = 0.030) independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells.