Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
J Immunol. 2021 Sep 15;207(6):1522-1529. doi: 10.4049/jimmunol.2100379. Epub 2021 Aug 18.
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 (1.51 [1.13, 2.01]), (1.72 [1.26, 2.34]), and 2DS1 (1.41 [1.04, 1.91]). Individuals with or and the HLA-CC2 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 , , , and are more likely to have AD, and the risk increased for and 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 gene allelic variation as well as consider cell-based measurements of KIR and the associated HLA class I epitopes.
特应性皮炎（AD）是一种与免疫失调相关的慢性疾病。NK 细胞功能先前与 AD 相关。NK 细胞直接通过杀伤细胞免疫球蛋白样受体（KIR）与多态性 HLA Ⅰ类配体变体相互作用。本研究旨在通过评估 KIR 基因的存在以及 KIR 基因与适当的 HLA Ⅰ类 KIR 特异性配体的相互作用的变化，来确定 NK 细胞功能与 AD 之间的潜在关联。使用来自 AD 病例对照研究的遗传学人类 DNA 对 HLA Ⅰ类 KIR 特异性配体和 KIR 基因的存在进行基因分型。在全队列中，发现 （1.51 [1.13, 2.01]）、 （1.72 [1.26, 2.34]）和 2DS1（1.41 [1.04, 1.91]）与 AD 风险增加相关。具有 或 且具有 HLA-CC2 表位的个体患 AD 的风险增加（分别为 1.74 [1.21, 2.51]和 1.48 [1.04, 2.12]）。HLA-B-21T（TT）前导序列增加了跨种族的 AD 风险。非裔美国人中具有 、 、 、和 更有可能患 AD，在存在适当的 HLA-C C2 表位的情况下， 与 风险增加。HLA-B*-21T 前导序列的个体患 AD 的风险也增加。未来的研究应集中在 基因等位基因变异上，并考虑 KIR 以及相关的 HLA Ⅰ类表位的细胞测量。
