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Psoriatic arthritis: review of potential biomarkers predicting response to TNF inhibitors

机译:银屑病关节炎:预测对TNF抑制剂反应的潜在生物标志物的回顾

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Abstract Psoriatic arthritis (PsA) is a chronic and painful inflammatory immune-mediated disease. It affects up to 40 of people with psoriasis and it is associated with several comorbidities such as obesity, diabetes, metabolic syndrome, and hypertension. PsA is difficult to diagnose because of its diverse symptoms, namely axial and peripheral arthritis, enthesitis, dactylitis, skin changes, and nail dystrophy. Different drugs exist to treat the inflammation and pain. When patients do not respond to conventional drugs, they are treated with biologic drugs. Tumour necrosis factor inhibitors (TNFi’s) are commonly given as the first biologic drug; beside being expensive, they also lack efficacy in 50 of patients. A biomarker predicting individual patient’s response to TNFi would help treating them earlier with an appropriate biologic drug. This study aimed to review the literature to identify potential biomarkers that should be investigated for their predictive ability. Several such biomarkers were identified, namely transmembrane TNFα (tmTNF), human serum albumin (HSA) and its half-life receptor, the neonatal Fc receptor (FcRn) which is also involved in IgG lifespan; calprotectin, high mobility group protein B1 (HMGB1) and advanced glycation end products (AGEs) whose overexpression lead to excessive production of pro-inflammatory cytokines; lymphotoxin α (LTα) which induces inflammation by binding to TNF receptor (TNFR); and T helper 17 (Th17) cells which induce inflammation by IL-17A secretion.
机译:摘要 银屑病关节炎(PsA)是一种慢性疼痛的炎症性免疫介导性疾病。它影响多达 40% 的银屑病患者,并与肥胖、糖尿病、代谢综合征和高血压等多种合并症有关。PsA 因其多种症状而难以诊断,即轴向和外周关节炎、附着点炎、指趾炎、皮肤变化和指甲营养不良。存在不同的药物来治疗炎症和疼痛。当患者对常规药物无反应时,他们接受生物药物治疗。肿瘤坏死因子抑制剂 (TNFi) 通常作为第一种生物药物;除了价格昂贵外,它们还缺乏对 50% 患者的疗效。预测个体患者对TNFi反应的生物标志物将有助于早期使用适当的生物药物进行治疗。本研究旨在回顾文献,以确定应研究其预测能力的潜在生物标志物。鉴定了几种这样的生物标志物,即跨膜TNFα(tmTNF)、人血清白蛋白(HSA)及其半衰期受体,新生儿Fc受体(FcRn),其也参与IgG寿命;钙卫蛋白、高迁移率组蛋白 B1 (HMGB1) 和晚期糖基化终产物 (AGEs),其过表达导致促炎细胞因子的过量产生;淋巴毒素α(LTα)通过与TNF受体(TNFR)结合诱导炎症;和辅助性 T 细胞 17 (Th17) 通过 IL-17A 分泌诱导炎症。

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