Human leukocyte antigen class-I variation is associated with atopic dermatitis: A case-control study

Margolis, David J.; Mitra, Nandita; Duke, Jamie L.; Berna, Ronald; Margolis, J.D.; Hoffstad, Ole; Kim, Brian; Yan, Albert C.; Zaenglein, Andrea L.; Fuxench, Zelma C. Chiesa; Dinou, Amalia; Wasserman, Jenna R.; Tairis, Nikolaos; Mosbruger, Timothy; Ferriola, Deborah; Damianos, Georgios; Kotsopoulou, Ioanna; Monos, D.

doi:10.1016/j.humimm.2021.04.001

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…The primary source of subjects for this study was the genetics of AD (GAD) cohort and details of this study were recently published (28,29). All subjects were examined and diagnosed by dermatologists with expertise in the diagnosis of AD.…”

Section: Primary Study Populationmentioning

confidence: 99%

“…HLA genotyping. DNA was collected using Oragene DNA collection kits (DNA Genotek, Ottawa, Canada) as previously reported (17,29,30,31). The three classic HLA class I genes (A, B, and C) were sequenced using targeted, amplicon-based next-generation sequencing (NGS) with Omixon Holotype HLA V2 kits (Budapest, Hungary) using Illumina MiSeq (San Diego, CA) using paired-end 2 Â 150 V2 chemistry.…”

Section: Dna Analysismentioning

confidence: 99%

“…The three classic HLA class I genes (A, B, and C) were sequenced using targeted, amplicon-based next-generation sequencing (NGS) with Omixon Holotype HLA V2 kits (Budapest, Hungary) using Illumina MiSeq (San Diego, CA) using paired-end 2 Â 150 V2 chemistry. Omixon Twin (7000 pairs per locus, v, 2.5.1) and GenDx NGSengine (300,000 pairs per sample) analyzed each set of Fastq files (17,29,31).…”

Section: Dna Analysismentioning

confidence: 99%

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Association of KIR Genes and MHC Class I Ligands with Atopic Dermatitis

Margolis

Mitra

Hoffstad

et al. 2021

The Journal of Immunology

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Atopic dermatitis (AD) is a chronic illness that is associated with immune dysregulation. NK cell function has previously been associated with AD. NK cells directly interact with polymorphic HLA class I ligand variants using killer cell Ig-like receptors (KIRs). The purpose of this study was to identify potential associations between NK cell function and AD by evaluating variation in the presence of KIR genes as well as KIR gene interactions with the appropriate HLA class I KIR–specific ligands. Human DNA from the genetics of AD case–control study was used to genotype HLA class I KIR–specific ligands and the presence of KIR genes. In the full cohort, an increased risk of AD was noted for KIR2DL5 (1.51 [1.13, 2.01]), KIR2DS5 (1.72 [1.26, 2.34]), and KIR2DS1 (1.41 [1.04, 1.91]). Individuals with KIR2DS5 or KIR2DS1 and the HLA-C*C2 epitope were at an increased risk of AD (1.74 [1.21, 2.51] and 1.48 [1.04, 2.12], respectively). The HLA-B*-21T (TT) leader sequence increased the risk of AD across ethnicity. African Americans with KIR2DL2, KIR2DS1, KIR2DL5, and KIR2DS5 are more likely to have AD, and the risk increased for KIR2DS1 and KIR2DS5 in the presence of appropriate HLA-C C2 epitope. The risk of AD also increased for individuals with the HLA-B*-21T leader sequence. Future studies should focus on KIR gene allelic variation as well as consider cell-based measurements of KIR and the associated HLA class I epitopes.

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Section: Primary Study Populationmentioning

confidence: 99%

Section: Dna Analysismentioning

confidence: 99%

Section: Dna Analysismentioning

confidence: 99%

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Association of KIR Genes and MHC Class I Ligands with Atopic Dermatitis

Margolis

Mitra

Hoffstad

et al. 2021

The Journal of Immunology

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“…DNA was collected using Oragene DNA collection kits (DNA Genotek, Ottawa Canada) as previously reported. [70][71][72][73] HLA Class I genes (-A, -B, and -C) were sequenced using targeted amplicon-based NGS as previously described. [71][72][73] We focused on HLA ligands known to interact with KIR genes studied.…”

Section: Discussionmentioning

confidence: 99%

“…[70][71][72][73] HLA Class I genes (-A, -B, and -C) were sequenced using targeted amplicon-based NGS as previously described. [71][72][73] We focused on HLA ligands known to interact with KIR genes studied. HLA-B leader sequence is de ned at location − 21 (amino acids T or M) of HLA-B.…”

Section: Discussionmentioning

confidence: 99%

Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and Atopic Dermatitis

Margolis

Mitra

Hoffstad

et al. 2022

Preprint

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Natural killer cells (NK) have been associated with the pathophysiology of atopic dermatitis (AD). NK function is regulated by killer cell Ig-like receptor family (KIR) receptors that interact with HLA ligands. The goal of this study was to focus on allelic variation in genes KIR2DL5, KIR2DS5, and KIR2DS1 with respect to AD. This was a case-control study of individuals with (n = 313) and without (n = 176) AD. Associations were estimated using logistic regression. Evaluations included interactions between KIR and known HLA ligand pairs. The prevalence of KIR2DL5 was 52.5% (95% CI: 48.0,57.0), KIR2DS5 was 33.0% (28.8,37.3), and KIR2DS1 was 33.6% (29.4,38.0). When compared to those who did not have KIR2DL5, homozygote individuals for KIR2DL5*001:01 were more likely to have AD (OR: 2.16 (95% CI:1.31,3.53) p = 0.0023). The effect of KIR2DL5*001:01 was similar in Whites and Blacks. The alleles from the other KIR genes of interest were not associated with AD. There is no known HLA ligand for KIR2DL5. However, the effect of KIR2DL5*001:01 increases in the presence of HLA-B *-21TT leader sequence (2.46(1.37,4.41) p = 0.0025) and HLA-C2 ligand (2.07 (1.37,4.41, p = 0.000002). This is the first study to explore KIR allelic variation in AD. KIR2DL5*001:01 allele is independently associated with an increased risk of AD.

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