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

Jarduli, Luciana Ribeiro; Alves, Hugo Vicentin; Souza-Santana, Fabiana Covolo de; Marcos, Elaine Valim Camarinha; Pereira, Ana Carla; Dias-Baptista, Ida Maria Foschiani; Fava, Vinicius M.; Mira, Marcelo Távora; Moraes, Milton Ozório; Virmond, Marcos da Cunha Lopes; Visentainer, Jeane Eliete Laguila

doi:10.1186/1471-2334-14-438

Cited by 15 publications

(12 citation statements)

References 18 publications

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“…Although Jarduli et al (2014) [19] have not found an association of the homozygous KIR2DL2 gene in the presence of the heterozygous HLA-C group C1/C2 ( KIR2DL2 / KIR2DL2/C1/C2 ) with leprosy, our analysis has shown a risk to the clinical form LL compared to the healthy subjects. We also showed that KIR2DL3/KIR2DL3/C1/C1 is strongly increased in BL patients over the contacts, but previous studies in Southern Brazil [20] and the Mid-West [19] did not show a significant association between KIR2DL3/KIR2DL3/C1/C1 and the susceptibility of BL.…”

Section: Discussioncontrasting

confidence: 86%

“…The cytotoxic function of NK cells on target cells is regulated through the balance between activating and inhibitory signals that results from the interaction of KIRs and their HLA class I ligands [15,16]. Thus, it is possible that KIR molecules play a significant role in controlling the immune response during infections, which would explain the associations observed between certain KIR genes and ankylosing spondylitis [17], Chagas disease [18] and leprosy [19,20].…”

Section: Introductionmentioning

confidence: 99%

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The impact of KIR/HLA genes on the risk of developing multibacillary leprosy

et al. 2019

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BackgroundKiller-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 findingsGenotyping 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/SignificanceOur 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.

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Section: Discussioncontrasting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The impact of KIR/HLA genes on the risk of developing multibacillary leprosy

et al. 2019

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“…KIR receptors of NK cells may contribute to the occurrence of different immunological and clinical responses to the same disease in a specific population [ 16 ]. Several studies have described the participation of KIR (and their ligands) in infectious diseases, such as AIDS [ 17 , 18 ], hepatitis C [ 19 , 20 ], tuberculosis [ 21 , 22 ], leprosy [ 23 , 24 ] and malaria [ 25 , 26 , 27 ]. KIR are also involved in autoimmune and inflammatory diseases such as pemphigus foliaceus, psoriasis, scleroderma, rheumatoid vasculitis and Crohn’s disease [ 28 , 29 , 30 , 31 , 32 ], as well as in many types of cancer [ 33 – 36 ] and the survival of transplant patients [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease

et al. 2015

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The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy—CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30–18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy.

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“…Higher frequency of inhibitory pairs it was present in Borderline patients when compared to the control group, and a higher frequency of activating pairs as compared to the LL group. It was realized multivariate analysis and 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 ( 66 ).…”

Section: Response Innate Immune In Leprosymentioning

confidence: 70%

Gene Association with Leprosy: A Review of Published Data

et al. 2016

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Leprosy is a chronic infectious disease caused by an obligate intracellular bacterium known as Mycobacterium leprae. Exposure to the bacillus is necessary, but this alone does not mean an individual will develop clinical symptoms of the disease. In recent years, several genes have been associated with leprosy and the innate immune response pathways converge on the main hypothesis that genes are involved in the susceptibility for the disease in two distinct steps: for leprosy per se and in the development of the different clinical forms. These genes participate in the sensing, main metabolic pathway of immune response activation and, subsequently, on the evolution of the disease into its clinical forms. The aim of this review is to highlight the role of innate immune response in the context of leprosy, stressing their participation in the signaling and targeting processes in response to bacillus infection and on the evolution to the clinical forms of the disease.

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

Cited by 15 publications

References 18 publications

The impact of KIR/HLA genes on the risk of developing multibacillary leprosy

The impact of KIR/HLA genes on the risk of developing multibacillary leprosy

Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease

Gene Association with Leprosy: A Review of Published Data

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