HLA-A Bw4-80I KIR 配体的银屑病患者生物药物疗效降低。

Reduced Efficacy of Biological Drugs in Psoriatic Patients with HLA-A Bw4-80I KIR Ligands.

机构信息

Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.

Immunogenetics Laboratory, Immunohematology and Transfusion Centre, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.

出版信息

Mol Diagn Ther. 2020 Jun;24(3):311-314. doi: 10.1007/s40291-020-00457-8.

DOI:10.1007/s40291-020-00457-8

PMID:32189206

Abstract

BACKGROUND

Biological drugs (biologics) are a highly effective therapy for the moderate to severe form of psoriasis, an immune-mediated dermatosis with a strong immunogenetic component. The interaction between human leukocyte antigen (HLA) class I ligands and killer immunoglobulin-like receptors (KIR) has a functional significance in the education of natural killer (NK) cells, and can thus influence the response to biologics.

OBJECTIVE

In this study, we investigated the impact of HLA-A and -B KIR ligands in the response to biologics in a cohort of psoriatic patients.

METHODS

Eighty-five patients with moderate to severe psoriasis treated with biologics (adalimumab, etanercept, infliximab, ustekinumab and secukinumab) were enrolled in the study. Clinical response was evaluated as patients attaining 50%, 75% or 90% reduction in the Psoriasis Area and Severity Index (PASI) (PASI 50, 75 or 90, respectively) over 6 months' follow-up. Poor response was defined as PASI 50, and in this case patients shifted to treatment with a different biologic. Fifty-two patients (61.2%) showed excellent response (PASI 90) to the first biologic, while 33 patients (38.8%), needed two or more biologics before reaching an excellent response (PASI 90) and were considered difficult to treat.

RESULTS

Only HLA-A Bw4-80I ligands were associated with the response to biologics; in particular, they were linked with reduced response both at univariable analysis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.19-8.07; p = 0.019) and multivariable analysis (OR 5.02, 95% CI 1.40-17.97; p = 0.013).

CONCLUSION

We suggest that the HLA-A Bw4-80I epitope could be a marker of reduced responsiveness to biologics. The possible reason for this is an increase of tumour necrosis factor (TNF)-α and the silencing of NK cells through the predominant interaction with the KIR3DL/S pair. HLA-KIR affinities might lead to a more efficient way to prescribe biologics.

摘要

背景

生物制剂（biologics）是中度至重度银屑病的一种非常有效的治疗方法，银屑病是一种具有强烈免疫遗传成分的免疫介导性皮肤病。人类白细胞抗原（HLA）I 类配体与杀伤细胞免疫球蛋白样受体（KIR）之间的相互作用在自然杀伤（NK）细胞的教育中具有功能意义，因此可以影响对生物制剂的反应。

目的

本研究旨在探讨 HLA-A 和 -B KIR 配体在银屑病患者对生物制剂反应中的作用。

方法

本研究纳入了 85 例接受生物制剂（阿达木单抗、依那西普、英夫利昔单抗、乌司奴单抗和司库奇尤单抗）治疗的中度至重度银屑病患者。通过评估患者在 6 个月随访期间达到银屑病面积和严重程度指数（PASI）降低 50%、75%或 90%（分别为 PASI50、75 和 90）的情况来评价临床反应。不良反应定义为 PASI50，在这种情况下，患者转为使用另一种生物制剂。52 例（61.2%）患者对第一种生物制剂有极好的反应（PASI90），而 33 例（38.8%）患者需要使用两种或更多种生物制剂才能达到极好的反应（PASI90），被认为难以治疗。

结果

只有 HLA-A Bw4-80I 配体与生物制剂的反应相关；特别是，在单变量分析（比值比 [OR] 3.11，95%置信区间 [CI] 1.19-8.07；p=0.019）和多变量分析（OR 5.02，95% CI 1.40-17.97；p=0.013）中，HLA-A Bw4-80I 配体与反应降低相关。造成这种情况的可能原因是肿瘤坏死因子（TNF）-α的增加和通过与 KIR3DL/S 对的主要相互作用导致 NK 细胞沉默。HLA-KIR 亲和力可能会导致一种更有效的生物制剂处方方法。