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KIR 等位基因变异与特应性皮炎随时间的缓解。

KIR Allelic Variation and the Remission of Atopic Dermatitis Over Time.

机构信息

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.

出版信息

Immunohorizons. 2023 Jan 1;7(1):30-40. doi: 10.4049/immunohorizons.2200095.

Abstract

Atopic dermatitis (AD) is a common chronic skin disease. Although generally thought to be a disease of T-cell dysregulation, recent studies have suggested that immune dysregulation of NK cells is also important. Killer cell Ig-like receptors (KIRs) are involved with NK cell regulation. The Pediatric Eczema Elective Registry is a U.S. nationwide longitudinal cohort with up to 10 y of follow-up in which 655 children had DNA available for full allelic KIR sequencing. Every 6 mo, AD activity was reported by Pediatric Eczema Elective Registry children. Using generalized estimating equations, we evaluated the association of KIR allelic variation in concert with known HLA binding ligands and whether the child reported AD in "remission" (no skin lesions and not using AD medication). KIR2DS4001:01 (odds ratio 0.53, 95% CI [0.32, 0.88]) and KIR2DL4001:02 (0.54, [0.33, 0.89]) in the presence of C04:01 had the largest effect on decreasing the likelihood of AD remission. The haplotype KIR 2DL4001:02 ∼ 2DS4001:01 ∼ 3DL2002:01 (0.77, [0.60, 0.99]) was also associated with a decreased likelihood of AD remission. Our findings add to the general body of evidence of a growing literature on the importance of NK cells with respect to the immunopathogenesis and natural history of AD.

摘要

特应性皮炎(AD)是一种常见的慢性皮肤病。虽然一般认为它是一种 T 细胞失调疾病,但最近的研究表明 NK 细胞的免疫失调也很重要。杀伤细胞免疫球蛋白样受体(KIRs)参与 NK 细胞的调节。儿科特应性皮炎选择登记处是一个美国全国性的纵向队列,最多有 10 年的随访时间,其中 655 名儿童有可供全等位基因 KIR 测序的 DNA。每 6 个月,儿科特应性皮炎选择登记处的儿童报告 AD 活动情况。我们使用广义估计方程,评估了 KIR 等位基因变异与已知 HLA 结合配体的协同作用,以及儿童是否报告 AD 处于“缓解”(无皮肤损伤且不使用 AD 药物)。在 C04:01 存在的情况下,KIR2DS4001:01(比值比 0.53,95%置信区间 [0.32, 0.88])和 KIR2DL4001:02(0.54,[0.33, 0.89])对降低 AD 缓解的可能性影响最大。KIR 2DL4001:02 ∼ 2DS4001:01 ∼ 3DL2002:01(0.77,[0.60, 0.99])的单倍型也与 AD 缓解可能性降低相关。我们的发现增加了越来越多的关于 NK 细胞在 AD 的免疫发病机制和自然史中的重要性的文献的一般证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1235/10563438/ed5a102e8d17/ih2200095f1.jpg

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