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目前可用的生物标志物在犬炎症性肠病中的临床应用

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs.

作者信息

Heilmann Romy M, Steiner Jörg M

机构信息

Small Animal Clinic, College of Veterinary Medicine, University of Leipzig, Leipzig, Saxony, Germany.

Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX.

出版信息

J Vet Intern Med. 2018 Sep;32(5):1495-1508. doi: 10.1111/jvim.15247. Epub 2018 Sep 17.

Abstract

Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food-responsive, antibiotic-responsive, or immunosuppressant-responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein-losing enteropathy. Disease-independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α -proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C-reactive protein, perinuclear anti-neutrophilic cytoplasmic antibodies, 3-bromotyrosine, N-methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

摘要

犬慢性炎症性肠病(CIE)是一组以胃肠道疾病的慢性持续性或复发性体征以及黏膜炎症的组织学证据为特征的疾病。这些CIE被分类为食物反应性、抗生素反应性或免疫抑制剂反应性肠病。对免疫调节治疗无临床反应的患者归为无反应性肠病,而有肠道蛋白丢失的犬归为蛋白丢失性肠病。在犬中建立了与疾病无关的临床评分系统,用于评估临床疾病严重程度和治疗期间的患者监测。组织病理学和常规临床病理检查结果通常无法区分CIE的亚组。治疗试验通常耗时较长,进一步的诊断测试通常至少具有最小程度的侵入性。能够有助于确定疾病的存在、起源部位、疾病进程的严重程度、对治疗的反应或这些因素组合的生物标志物,对于患有CIE的犬在临床上将是有用的。本文总结了过去十年中在患有CIE的犬中评估的以下生物标志物,并严格评估了它们在患有CIE的犬中的潜在临床应用价值:功能生物标志物(钴胺素、甲基丙二酸、叶酸、α-蛋白酶抑制剂、免疫球蛋白A)、生化生物标志物(C反应蛋白、核周抗中性粒细胞胞浆抗体、3-溴酪氨酸、N-甲基组胺、钙卫蛋白、S100A12、晚期糖基化终产物可溶性受体、细胞因子和趋化因子、碱性磷酸酶)、微生物组生物标志物(微生物组变化、生态失调指数)、代谢组生物标志物(血清代谢组)、遗传生物标志物(基因组标记物、基因表达变化)和细胞生物标志物(调节性T细胞)。此外,还简要回顾了诊断测试的重要性能标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bae/6189362/9bc1cb285316/JVIM-32-1495-g001.jpg

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