PMID- 31525196 OWN - NLM STAT- MEDLINE DCOM- 20200110 LR - 20200110 IS - 1935-2735 (Electronic) IS - 1935-2727 (Print) IS - 1935-2727 (Linking) VI - 13 IP - 9 DP - 2019 Sep TI - The impact of KIR/HLA genes on the risk of developing multibacillary leprosy. PG - e0007696 LID - 10.1371/journal.pntd.0007696 [doi] LID - e0007696 AB - BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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. FAU - Alves, Hugo Vicentin AU - Alves HV AUID- ORCID: 0000-0002-3106-8820 AD - Laboratory of Immunogenetics, Department of Basic Health Sciences, Maringa State University (UEM), Parana, Brazil. AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - de Moraes, Amarilis Giaretta AU - de Moraes AG AD - Laboratory of Immunogenetics, Department of Basic Health Sciences, Maringa State University (UEM), Parana, Brazil. AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - Pepineli, Afonso Carrasco AU - Pepineli AC AD - Laboratory of Immunogenetics, Department of Basic Health Sciences, Maringa State University (UEM), Parana, Brazil. AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - Tiyo, Bruna Tiaki AU - Tiyo BT AD - Laboratory of Immunogenetics, Department of Basic Health Sciences, Maringa State University (UEM), Parana, Brazil. AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - de Lima Neto, Quirino Alves AU - de Lima Neto QA AUID- ORCID: 0000-0003-3313-7567 AD - Laboratory of Immunogenetics, Department of Basic Health Sciences, Maringa State University (UEM), Parana, Brazil. AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - Santos, Thais da Silva AU - Santos TDS AUID- ORCID: 0000-0002-0227-131X AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - Teixeira, Jorge Juarez Vieira AU - Teixeira JJV AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - Ambrosio-Albuquerque, Eliane P AU - Ambrosio-Albuquerque EP AD - Department of Biotechnology, Cell Biology and Genetics, Maringa State University (UEM), Parana, Brazil. FAU - Sell, Ana Maria AU - Sell AM AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. FAU - Visentainer, Jeane Eliete Laguila AU - Visentainer JEL AD - Laboratory of Immunogenetics, Department of Basic Health Sciences, Maringa State University (UEM), Parana, Brazil. AD - Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, Maringa State University (UEM), Parana, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190916 PL - United States TA - PLoS Negl Trop Dis JT - PLoS neglected tropical diseases JID - 101291488 RN - 0 (HLA Antigens) RN - 0 (Receptors, KIR) SB - IM MH - Adult MH - Aged MH - Brazil/epidemiology MH - Case-Control Studies MH - Female MH - *Genetic Predisposition to Disease MH - Genotype MH - HLA Antigens/*genetics MH - Humans MH - Leprosy, Multibacillary/epidemiology/*genetics MH - Male MH - Middle Aged MH - Neglected Diseases MH - Receptors, KIR/*genetics PMC - PMC6762192 COIS- The authors have declared that no competing interests exist. EDAT- 2019/09/17 06:00 MHDA- 2020/01/11 06:00 PMCR- 2019/09/16 CRDT- 2019/09/17 06:00 PHST- 2019/04/03 00:00 [received] PHST- 2019/08/08 00:00 [accepted] PHST- 2019/09/26 00:00 [revised] PHST- 2019/09/17 06:00 [pubmed] PHST- 2020/01/11 06:00 [medline] PHST- 2019/09/17 06:00 [entrez] PHST- 2019/09/16 00:00 [pmc-release] AID - PNTD-D-19-00474 [pii] AID - 10.1371/journal.pntd.0007696 [doi] PST - epublish SO - PLoS Negl Trop Dis. 2019 Sep 16;13(9):e0007696. doi: 10.1371/journal.pntd.0007696. eCollection 2019 Sep.