Inhibitory <i>KIR3DL1</i>
 alleles are associated with psoriasis

Ahn, Richard; Moslehi, Homayoun; Martin, Maureen P.; Abad-Santos, Matthew; Bowcock, Anne M.; Carrington, Mary; Liao, Wilson

doi:10.1111/bjd.14081

Cited by 32 publications

(30 citation statements)

References 15 publications

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“…However, MHC class I have other important immunoregulatory functions, including binding and regulation of natural killer (NK) cells through killer cell immunoglobulin-like receptors (KIRs) or regulation of antigen presenting cells (APCs) through leukocyte immunoglobulin-like receptors (LILR). We have previously shown that HLA-B can mediate psoriasis risk through interaction with KIRs (Ahn et al, 2016). Here, we demonstrate that HLA-B can also mediate psoriasis susceptibility through differential binding to LILRs.…”

Section: Introductionsupporting

confidence: 51%

“…Similarly, a compound genotype associated with delayed progression of HIV to AIDS (KIR3DS1 plus HLA-B Bw4-80I) also increases psoriasis susceptibly (Chen et al, 2012). Interactions of HLA to certain KIR molecules, such as KIR3DL1, have been shown to be beneficial in control of HIV (Martin et al, 2002), but have also been associated with psoriasis susceptibility (Ahn et al, 2016). Moreover, a variant upstream of HLA-C associated with HLA-C expression was shown to have significant protective effects on the control of HIV; at the same time, this variant was associated with increased susceptibility to Crohn's disease (Apps et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility

Yanovsky

Chen

Leslie

et al. 2019

Preprint

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Genetic variation within the major histocompatibility complex (MHC) class I is a well-known risk factor for psoriasis. While the mechanisms behind this variation are still being fully elucidated, human leukocyte antigen (HLA) presentation of auto-antigens as well as the interaction of HLA-B with killer cell immunoglobulin-like receptors (KIRs) have been shown to contribute to psoriasis susceptibility. Here we demonstrate that the interaction of HLA class I molecules with leukocyte immunoglobulin-like receptors (LILR), a related group of immunomodulatory receptors primarily found on antigen presenting cells, also contributes to psoriasis susceptibility. We used previously characterized binding capacities of HLA-A, HLA-B, and HLA-C allotypes to two inhibitory LILRs, LILRB1 and LILRB2, to investigate the effect of LILRB1/2 binding in two large genome wide association study cohorts of psoriasis patients and controls (N = 10,069). We found that the strength of binding of LILRB2 to HLA-B was inversely associated with psoriasis risk (p = 2.34E-09, OR [95% CI], 0.41 [0.30-0.55]) independent of individual class I or II allelic effects. We thus propose that weak binding of inhibitory LILRB2 to HLA-B may play a role in patient susceptibility to psoriasis via increased activity of antigen presenting cells.

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Section: Introductionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility

Yanovsky

Chen

Leslie

et al. 2019

Preprint

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“…Genetic studies that analyse KIR allelic variation are increasingly common (Ahn et al, 2016; Bari et al, 2013; Martin et al, 2007; Nakimuli et al, 2015; Nemat-Gorgani et al, 2018). Of equal importance, is the need to develop methods that allow us to characterise how these allelic variants contribute to functional differences at the cellular level and ultimately cause pathology.…”

Section: Discussionmentioning

confidence: 99%

High-resolution genetic and phenotypic analysis of KIR2DL1 alleles and their association with pre-eclampsia

Huhn

Chazara

Ivarsson

et al. 2018

Preprint

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Killer-cell immunoglobulin-like receptor (KIR) genes are inherited as haplotypes, expressed by NK cells and linked to outcomes of infectious diseases and pregnancy. Understanding how genotype relates to phenotype is difficult because of the extensive diversity of the KIR family. Indeed, high-resolution KIR genotyping and phenotyping in single NK cells in the context of disease association is lacking. Here, we describe a new method to separate NK cells expressing allotypes of the KIR2DL1 gene carried by the KIR A haplotype (KIR2DL1A) from those expressing KIR2DL1 alleles carried by the KIR B haplotype (KIR2DL1B). We find that in KIR AB heterozygous individuals, different KIR2DL1 allotypes can be detected both in peripheral blood and in uterine single NK cells. Using this new method, we demonstrate that both blood and uterine NK cells co-dominantly express KIR2DL1A and KIR2DL1B allotypes, but with a predominance of KIR2DL1A variants, which associate with enhanced NK cell function. In a case-control study of pre-eclampsia, we show that KIR2DL1A, not KIR2DL1B, associates with increased disease risk. This method will facilitate our understanding of how individual KIR2DL1 allelic variants affect NK cell function and contribute to disease risk.

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“…Similarly, polymorphism in the extracellular domain of KIR2DL1 influences the binding affinity to HLA‐C2 34, 40. Over 200 associations of KIR genes with disease resistance or susceptibility are published,56, 73 and the handful studied at high resolution are proving informative 58, 74, 75, 76. The field is therefore ripe for harvesting new information through in‐depth analyses 68, 77…”

Section: Kir Geneticsmentioning

confidence: 99%

“…34,40 Over 200 associations of KIR genes with disease resistance or susceptibility are published, 56,73 and the handful studied at high resolution are proving informative. 58,[74][75][76] The field is therefore ripe for harvesting new information through in-depth analyses. 68,77 KIR imputation A statistical model that infers KIR genotypes from wholegenome single nucleotide polymorphism data has been developed with about 97% accuracy for the majority of KIR genes, and can distinguish the broad A/B haplotypes.…”

Section: Kir Allelic Variationmentioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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Inhibitory KIR3DL1 alleles are associated with psoriasis

Cited by 32 publications

References 15 publications

The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility

The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility

High-resolution genetic and phenotypic analysis of KIR2DL1 alleles and their association with pre-eclampsia

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

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