Influence of KIR genes and their HLA ligands in the pathogenesis of leprosy in a hyperendemic population of Rondonópolis, Southern Brazil.

Luciana Ribeiro Jarduli,Marcos Da Cunha Lopes Virmond,Ida Maria Foschiani Dias-Baptista,Jeane Eliete Laguila Visentainer,Elaine Valim Camarinha Marcos,Ana Carla Pereira,Milton Ozório Moraes,Vinícius Medeiros Fava,Hugo Vicentin Alves,Fabiana Covolo De Souza-Santana,Marcelo Távora Mira

doi:10.1186/1471-2334-14-438

Abstract

BackgroundThe objective of this study was to investigate the association between KIR genes and the immunopathogenesis of leprosy.MethodsThe types of KIR and HLA genes were evaluated by PCR-SSOP-Luminex in 408 patients with leprosy and 413 healthy individuals. Statistical analysis was performed using the Chi-square or Fisher’s exact test and stepwise multivariate analysis.ResultsThere was a higher frequency of activating KIR genes (KIR2DS1, 2DS2 and 3DS1) together with their HLA ligands in the tuberculoid (TT) group as compared to the lepromatous leprosy (LL) group. KIR2DL2/2DL2-C1 was more frequent in the patient, TT and LL groups than in the control group. Borderline patients presented a higher frequency of inhibitory pairs when compared to the control group, and a higher frequency of activating pairs as compared to the LL group. Multivariate analysis confirmed the associations and demonstrated that being a female is a protective factor against the development of the disease per se and the more severe clinical form.ConclusionsThis study showed that activating and inhibitory KIR genes may influence the development of leprosy – in particular, activating genes may protect against the more aggressive form of the disease – thereby demonstrating the role of NK cells in the immunopathology of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-438) contains supplementary material, which is available to authorized users.

Highlights

The objective of this study was to investigate the association between KIR genes and the immunopathogenesis of leprosy
The most widely used classification model for the disease is that of Ridley-Jopling, which divides the disease into five polar and interpolar forms: Tuberculoid (TT), Borderline-Tuberculoid (BT), Borderline-Borderline (BB), Borderline-lepromatous leprosy (BL) and Lepromatous leprosy (LL) [3]
Both the mean and median ages were similar among all groups (Total Patients, LL, Borderline, the tuberculoid (TT) and Control), demonstrating a good match between cases and controls

Summary

Introduction

The objective of this study was to investigate the association between KIR genes and the immunopathogenesis of leprosy. Research has been aimed at better understanding the genetics of susceptibility to the different clinical forms of leprosy. While some loci affect the intrinsic susceptibility to leprosy itself, others modify the clinical form of the disease [5]. Among the candidate genes for an individual’s susceptibility or resistance to leprosy are the KIR (Killer Immunoglobulin-Like Receptor) genes. These genes span over approximately 150 Kb of the LCR (Leukocyte Receptor Complex) region of chromosome 19q13.4, which encodes KIRs, members of a group of regulatory molecules present on the surface of NK (Natural Killer) cells [6]

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