Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

Background ankylosing spondylitis (aS) is a complex chronic inflammatory disease strongly associated with the majority of human leucocyte antigen (Hla)-B27 alleles. Hla-e molecules are non-classical major histocompatibility complex (MHc) class i molecules that specifically interact with the natural killer receptors nKg2a (inhibitory) and nKg2c (activating), and have been recently proposed to be involved in aS pathogenesis.‘’ Objective to analyse the expression of Hla-e and the cD94/nKg2 pair of receptors in Hla-B27-positive patients with aS and healthy controls (Hc) bearing the aS-associated B*2705 and the non-aS-associated B*2709 alleles. Methods the level of surface expression of Hla-e molecules on cD14+ peripheral blood mononuclear cell was evaluated in 21 Hla-B*2705 patients with aS, 12 Hla-B*2705 Hc, 12 Hla-B*2709 Hc and 6 Hla-B27- negative Hc using the monoclonal antibody MeM-e/08 by quantitative cytofluorimetric analysis. the percentage and density of expression of Hla-e ligands nKg2a and nKg2c were also measured on cD3−cD56+ nK cells. Results Hla-e expression in cD14+ cells was significantly higher in patients with aS (587.0, iQr 424–830) compared with B*2705 Hc (389, iQr 251.3–440.5; p=0.0007), B*2709 Hc (294.5, iQr 209.5–422; p=0.0004) and Hla-B27-negative Hc (380, iQr 197.3–515.0; p=0.01). a higher number of nK cells expressing nKg2a compared with nKg2c were found in all cohorts analysed, as well as a higher cell surface density. Conclusion the higher surface level of Hla-e molecules in patients with aS compared with Hc, concurrently with a prevalent expression of nKg2a, suggests that the crosstalk between these two molecules might play a role in aS pathogenesis, accounting for the previously reported association between Hla-e and aS.