02028nas a2200229   4500000000100000008004100001100001300042700001400055700001600069700001200085700001300097700001400110700001700124700002800141700001200169700002000181245008200201300001300283490000700296520148100303022001401784       2019                            d1 aAlves HV1 aMoraes AG1 aPepineli AC1 aTiyo BT1 aNeto QAL1 aSantos TS1 aTeixeira JJV1 aAmbrosio-Albuquerque EP1 aSell AM1 aVisentainer JEL00aThe impact of KIR/HLA genes on the risk of developing multibacillary leprosy.  ae00076960 v133 a<p><strong>BACKGROUND: </strong>Killer-cell immunoglobulin-like receptors (KIRs) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen (HLA) class I molecules. Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical responses to infectious diseases. Leprosy is a chronic neglected disease, both disabling and disfiguring, caused mainly by Mycobacterium leprae. In this case-control study, we examined the influence of KIRs and HLA ligands on the development of multibacillary leprosy.</p>

<p><strong>METHODOLOGY/PRINCIPAL FINDINGS: </strong>Genotyping of KIR and HLA genes was performed in 264 multibacillary leprosy patients and 518 healthy unrelated controls (238 healthy household contacts and 280 healthy subjects). These are unprecedented results in which KIR2DL2/KIR2DL2/C1/C2 and KIR2DL3/2DL3/C1/C1 indicated a risk for developing lepromatous and borderline leprosy, respectively. Concerning to 3DL2/A3/A11+, our study demonstrated that independent of control group (contacts or healthy subjects), this KIR receptor and its ligand act as a risk factor for the borderline clinical form.</p>

<p><strong>CONCLUSIONS/SIGNIFICANCE: </strong>Our finding suggests that synergetic associations of activating and inhibitory KIR genes may alter the balance between these receptors and thus interfere in the progression of multibacillary leprosy.</p>
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