Baseline Expression of Immune Gene Modules in Blood is Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease Patients.
Baseline Expression of Immune Gene Modules in Blood is Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease Patients.
复制标题
血液中免疫基因模块的基线表达与克罗恩病患者对抗 TNF 治疗的主要反应相关。
DOI：
10.1093/ecco-jcc/jjad166
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Bai BYH
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文献类型：
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作者：
Bai BYH
背景与目的抗肿瘤坏死因子治疗被广泛应用于炎症性肠病的治疗，但许多患者对诱导治疗无反应。我们的目的是确定抗肿瘤坏死因子单抗[英夫利昔单抗和阿达莫单抗]的主要应答者和主要无应答者之间的血液基因表达差异，并根据血液基因表达和临床数据预测应答状态。方法克罗恩病个体化抗肿瘤坏死因子治疗[PANS]研究是一项针对抗肿瘤坏死因子初治克罗恩病患者抗肿瘤坏死因子治疗结果的前瞻性观察队列研究[ClinicalTrials.gov ID：NCT03088449]。结果在调整临床变量和估计血细胞组成后，抗 = 应答者的主要组织相容性复合体、抗原提呈、髓系细胞富集型受体和其他天然免疫基因模块的基线表达显著高于无应答者。从基线到第14周的表达变化通常方向一致，但在应答者中幅度更大[即放大]，但干扰素相关基因在无应答者中唯一上调。在第14周观察到的应答者和无应答者之间的表达差异在30周和54周保持不变。从基线临床数据、细胞组成和模块表达预测应答状态不佳。结论基线基因模块表达与裤子患者对抗肿瘤坏死因子治疗的初始应答相关。然而，这些基线表达差异并不能预测临床使用的足够敏感性的反应。
Background and AimsAnti-tumour necrosis factor [anti-TNF] therapy is widely used for the treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies [infliximab and adalimumab], and to predict response status from blood gene expression and clinical data.MethodsThe Personalised Anti-TNF Therapy in Crohn’s Disease [PANTS] study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF-naive Crohn’s disease patients [ClinicalTrials.gov identifier: NCT03088449]. Blood gene expression in 324 unique patients was measured by RNA-sequencing at baseline [week 0], and at weeks 14, 30, and 54 after treatment initiation [total sample size = 814].ResultsAfter adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders vs non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude [i.e. amplified] in responders, but interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at weeks 30 and 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor.ConclusionsBaseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.