维生素 D 与 α4β7+免疫表型相关，并可预测炎症性肠病患者接受 vedolizumab 治疗失败。
Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.
机构信息
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.
Chan Zuckerberg Biohub, San Francisco, CA, USA.
出版信息
J Crohns Colitis. 2021 Dec 18;15(12):1980-1990. doi: 10.1093/ecco-jcc/jjab114.
BACKGROUND AND AIMS
Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4β7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4β7 immunophenotypes and risk of vedolizumab [anti-α4β7] failure in IBD.
METHODS
We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizumab-naïve patients with IBD [N = 48]. We analysed whole-genome mucosal gene expression [GSE73661] from GEMINI I and GEMINI long-term safety [LTS] to determine the association between vitamin D receptor [VDR] and integrin alpha-4 [ITGA4] and beta-7 [ITGB7] genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort [N = 252] with logistic regression.
RESULTS
Immunophenotyping revealed that higher 25[OH]D was associated with decreased α4β7+ peripheral blood mononuclear cells [R = -0.400, p <0.01] and α4β7+ intestinal leukocytes [R = -0.538, p = 0.03]. Serum 25[OH]D was inversely associated with α4β7+ peripheral B cells and natural killer [NK] cells and α4β7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25[OH]D <25 ng/mL was associated with increased vedolizumab primary non-response during induction (odds ratio [OR] 26.10, 95% confidence interval [CI] 14.30-48.90, p <0.001) and failure at 1-year follow-up [OR 6.10, 95% CI 3.06-12.17, p <0.001].
CONCLUSIONS
Low serum 25[OH]D is associated with α4β7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD.
PODCAST
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背景与目的
维生素 D 可下调免疫细胞上肠道趋向性整合素 α4β7 的体外表达。其在炎症性肠病（IBD）患者中的临床相关性尚不清楚。我们检验了如下假设，即维生素 D 与 α4β7 免疫表型和 vedolizumab（抗-α4β7）治疗失败风险相关。
方法
我们对 vedolizumab 初治 IBD 患者[共 48 例]的外周血和肠道免疫细胞进行单细胞免疫表型分析，采用质谱流式细胞术（CyTOF）。我们分析了 GEMINI I 和 GEMINI 长期安全性（LTS）中的全基因组黏膜基因表达[GSE73661]，以确定维生素 D 受体（VDR）与整合素 α-4（ITGA4）和 β-7（ITGB7）基因之间的关联。我们采用逻辑回归，对 252 例回顾性和前瞻性 IBD 队列（均接受 vedolizumab 治疗）的患者进行低治疗前维生素 D 与 vedolizumab 治疗失败的相关性分析。
结果
免疫表型分析显示，25（OH）D 水平越高，外周血单个核细胞中 α4β7+细胞[R = -0.400，p <0.01]和肠道白细胞中 α4β7+细胞[R = -0.538，p = 0.03]越少。血清 25（OH）D 与外周血 B 细胞和自然杀伤（NK）细胞以及肠道 B 细胞、NK 细胞、单核细胞和巨噬细胞中的 α4β7+细胞呈负相关。黏膜 VDR 表达与 ITGA4 和 ITGB7 表达呈负相关。多变量分析显示，25（OH）D <25 ng/mL 与诱导期 vedolizumab 原发性无应答增加（比值比[OR] 26.10，95%置信区间[CI] 14.30-48.90，p <0.001）和 1 年随访时治疗失败（OR 6.10，95% CI 3.06-12.17，p <0.001）相关。
结论
低血清 25（OH）D 与 α4β7+免疫表型相关，并可预测 IBD 患者 vedolizumab 治疗失败的未来风险。
播客
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