Killer Immunoglobulin-like Receptors (KIR) and their HLA-ligands in Italian Paroxysmal Nocturnal Haemoglobinuria (PNH) patients

PNH is a haematopoietic disorder characterized by expansion of PIG-A-defective progenitor(s). Immune-dependent mechanisms, likely involving a deranged T-cell-dependent autoimmune response have been consistently associated with the selection/dominance of PNH precursors. Natural Killer (NK) lymphocytes might participate in PNH pathogenesis, but their role is still controversial. NK activity is dependent on the balance between activating and inhibiting signals. Key component in such regulatory network is represented by Killer Immunoglobulin-like Receptors (KIR). KIR are also involved in the regulation of adaptive cytotoxic T cell response and associated with autoimmunity. This study investigated on the frequency of KIR genes and their known HLA ligands in 53 PNH Italian patients. We observed increased frequency of genotypes characterised by ≤2 activating KIR as well as by the presence of an inhibitory/activating gene ratio ≥3.5. In addition, an increased matching between KIR-3DL1 and its ligand HLA-Bw4 was found. These genotypes might be associated with lower NK-dependent recognition of stress-related self-molecules; this is conceivable with the hypothesis that an increased availability of specific T-cell targets, not cleared by NK cells, could be involved in PNH pathogenesis. These data may provide new insights into autoimmune PNH pathogenesis.