Wesley Medical Research, Toowong, Australia.
Expert Rev Clin Immunol. 2022 Jan;18(1):75-91. doi: 10.1080/1744666X.2021.2006636.
Recent patient studies have shown that gluten-free diet is less effective in treating celiac disease than previously believed, and additionally patients remain vulnerable to gluten-induced acute symptoms and systemic cytokine release. Safe and effective pharmacological adjuncts to gluten-free diet are in preclinical and clinical development. Clear understanding of the pathogenesis of celiac disease is critical for drug target identification, establishing efficacy endpoints and to develop noninvasive biomarkers suitable to monitor and potentially diagnose celiac disease.
The role and clinical effects of CD4+ T cells directed against deamidated gluten in the context of an 'adaptive immune paradigm' are reviewed. Alternative hypotheses of gluten toxicity are discussed and contrasted. In the context of recent patient studies, implications of the adaptive immune paradigm for future strategies to prevent, diagnose, and treat celiac disease are outlined.
Effective therapeutics for celiac disease are likely to be approved and necessitate a variety of new clinical instruments and tests to stratify patient need, monitor remission, and confirm diagnosis in uncertain cases. Sensitive assessments of CD4+ T cells specific for deamidated gluten are likely to play a central role in clinical management, and to facilitate research and pharmaceutical development.
最近的患者研究表明，与之前的认知相比，无麸质饮食在治疗乳糜泻方面的效果较差，此外，患者仍然容易受到麸质诱导的急性症状和全身细胞因子释放的影响。安全有效的无麸质饮食辅助药物正在临床前和临床开发中。对乳糜泻发病机制的清晰理解对于药物靶点的识别、建立疗效终点以及开发适合监测和潜在诊断乳糜泻的非侵入性生物标志物至关重要。
本文回顾了针对脱酰胺麸质的 CD4+T 细胞在“适应性免疫范式”背景下的作用和临床效果。讨论并对比了麸质毒性的替代假说。在最近的患者研究背景下，概述了适应性免疫范式对未来预防、诊断和治疗乳糜泻的策略的影响。
有效的乳糜泻治疗药物很可能获得批准，并需要各种新的临床仪器和测试来对患者的需求进行分层，监测缓解情况，并在不确定的情况下确认诊断。针对脱酰胺麸质的 CD4+T 细胞的敏感评估可能在临床管理中发挥核心作用，并促进研究和药物开发。
