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

Abstract

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.

High-Resolution Characterization of KIR Genes in a Large North American Cohort Reveals Novel Details of Structural and Sequence Diversity

“…Transduction of NK cell activating and inhibitory signals is achieved by a subset of human leukocyte antigen (HLA) class I molecules, which serve as KIR ligands (22)(23)(24). These two interacting molecule families evolve as a unique and integrated system (25)(26)(27)(28), and combinations of KIR and HLA have been associated with numerous diseases (29)(30)(31)(32), including autoimmune disorders (33)(34)(35)(36), malignancies (37)(38)(39) and infections (40)(41)(42)(43). Combinations of KIR and HLA class I also affect placentation and the success of reproduction (44)(45)(46)(47).…”

Recombinant polypeptide of Mycobacterium leprae as a potential tool for serological detection of leprosy

“…The clinical course of disease progression in leprosy depends on the individual immune system (Alves et al 2019). Genetic predisposition has been implicated to play a role in both disease susceptibility and host immune responses (Shankarkumar et al 2003).…”

An immunogenetic view of COVID-19

“…Among all HLA class Ia molecules, HLA-C originated more recently and evolved to primarily bind KIR and regulate NK cell response, while HLA-A and HLA-B retained their primary function as T cell ligands ( Older Aguilar et al, 2010 ). Combinations of KIR-HLA have been associated with diseases ( Williams et al, 2005 ; Kulkarni et al, 2008 ; Augusto, 2016 ; Boudreau and Hsu, 2018 ), including infection ( Martin et al, 2007 ; Podhorzer et al, 2017 ; Alves et al, 2019 ; Auer et al, 2020 ), cancer ( Middleton et al, 2007 ; Al Omar et al, 2010 ; Kim et al, 2014 ), and autoimmunity ( Suzuki et al, 2004 ; Augusto et al, 2012 ; Hollenbach et al, 2016 ; Anderson et al, 2020 ).…”