92-P: KIR2DS2 GENE CONFERS SUSCEPTIBILITY TO LEPROMATOUS LEPROSY (LL) IN MEXICAN PATIENTS

Aim Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae that occurs primarily in developing countries in tropical and warm temperate regions. The disease displays an immunological spectrum ranging from tuberculoid leprosy (TT) to LL, showing a complete absence of a specific cellular immune response. We and others have published the contribution of HLA Class II genes in LL expression and the participation of HLA-DQ alleles as Is genes. The goal of this study was to investigate the role of KIR genes in the expression of leprosy in Mexican LL patients. Methods One hundred and six LL patients and 124 healthy controls from the same endemic area were included. LL was diagnosed according to clinical, immunologic and histological criteria. DNA was extracted from peripheral blood. Typing of 14 KIR genes was done using a SSP system with four multiplex reactions. HLA typing was performed using a Luminex PCR-SSOP method. The frequency of each KIR gene was determined by direct counting. A & B haplotypes were deduced from the genotype data. The statistical comparison was done using the X2Y. Results The presence of the activating gene 2DS2 was found associated with susceptibility to LL (Gf = 59.43% in P. Vs. 43.54% in C., p = 0.02, OR = 1.89). No differences were found in the A or B haplotype groups or their combinations. The KIR-HLA gene combinations were not found deviated; the C4 and T4 cluster depicted no differences either. Conclusions Our results confirm the involvement of KIR genes in susceptibility to LL, with a variable contribution depending on ethnicity. In a study done in Brazilian patients, 2DS2 was found significantly increased in TT; the authors suggested a possible protective role against the severe form of leprosy. Nonetheless, in Mexicans, 2DS2 is associated with LL. An enhanced NK and T cells activation may promote bacilli dissemination and contribute to the severity in LL, due to the release of cytokines that suppress the CMI and the innate response to the infection.