Polimorfismos do complexo de genes KIR predispõem à hanseníase e modulam seu desenvolvimento para a forma paucibacilar

Abstract

Leprosy is a chronic and granulomatous disease of the skin and peripheral nerves, that infects mainly macrophages and Schwann cells. The World Health Organization classifies leprosy in two polar forms: multibacillary and paucibacillary, according to the bacillary index and the immune response from the host. Natural killer (NK) cells play an important role during infection, since it constitutes the first defense against intracellular organisms. NK cells utilize many types of cellular surface receptors, as killer immunoglobulin-like receptors (KIR) that may inhibit or activate NK cytolytic response, through recognizing major histocompatibility complex (MHC) class I molecules on the target cell. In this case-control study, the presence o absence of 15 KIR genes and their HLA-C ligands were investigated, aiming to describe their genotypic variability, association with leprosy infection and clinical progression. Genotyping of KIR repertoire and HLA-C NK1 and NK2 groups was performed by PCR-SSP in 105 patients and 104 controls. KIR2DL2 and KIR2DL3, in the presence of its HLA-Cw ligand, may predispose to leprosy (p=0,046; X²= 3,97; OR=1.99; 95% CI=1.00-3.97). Additionally, worldwide leprosy prevalence and KIR2DL2 frequencies were positively correlated. This find, along with the association between KIR2DL3 and tuberculosis described by other authors, suggests that these inhibitory receptor genes predispose to the disease. Besides, KIR2DS2 was associated with the development paucibacillary leprosy (p=0,009; X²= 7,23; OR=3,7; 95% CI=1,37-9,96), possibly modulating the development toward the mild form of the disease.