Nyborg Gunhild Alvik
Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, 0424, Norway.
Recent Adv Inflamm Allergy Drug Discov. 2025;19(2):221-235. doi: 10.2174/0127722708317244240919113305.
Anecdotal reports describe patients with concurrent idiopathic inflammatory myopathy (IIM) and celiac disease (CeD) in whom the introduction of a gluten-free diet led to dramatic improvement of myositis. We first systematically reviewed all peer-reviewed publications on concomitant IIM and duodenal biopsy-verified CeD. The collected evidence was suggestive of associations between myositis disease activity and gluten exposure in some patients with IIM-CeD.
To investigate possible explanations for the observations, an exploratory review of basic pathophysiological relationships between IIM and gluten-related disorders was performed using a combined strategy of systematic and non-systematic literature searches and forward and backward citation tracking.
The investigations revealed close pathophysiological associations between IIM and the autoimmune gluten-related disorders CeD, dermatitis herpetiformis, and gluten ataxia. Common traits include shared genetic predisposition through HLA-DQ2.5/-DQ8, disease activity-associated autoantibodies, histopathological parallels with inflammatory cell infiltrates, and similarly distributed structural homologous transglutaminases (TGs). HLA-DQ2.5-restricted gluten-specific CD4+ T cells of a rare, uniform phenotype are reported in CeD and connective tissue disease. Expanded T-cell clones with identical phenotypes and CDR3β motifs indicate the presence of a continuous, antigen-driven T-cell response.
The investigations revealed that the main components involved in the adaptive immune response in the CeD gut may be present in HLA-DQ2.5+/-DQ8+ IIM muscle. The collected evidence supports the notion that in some genetically predisposed patients with IIM, gluten may act as an exogenous antigen driving myositis. Further Research/Clinical Implications: To test the above hypothesis, clinical trials combined with immunological studies are needed. Meanwhile, the inclusion of HLA-DQ typing may be justified, and subsequent small-intestinal biopsies in HLA-DQ2.5/8+ individuals with IIM.
有轶事报道称，患有特发性炎性肌病（IIM）和乳糜泻（CeD）的患者在采用无麸质饮食后，肌炎症状显著改善。我们首先系统回顾了所有关于IIM与经十二指肠活检证实的CeD并存的同行评审出版物。收集到的证据表明，在一些IIM-CeD患者中，肌炎疾病活动与麸质暴露之间存在关联。
为探究这些观察结果的可能解释，我们采用系统和非系统文献检索以及前后向引文追踪相结合的策略，对IIM与麸质相关疾病之间基本病理生理关系进行了探索性综述。
研究揭示了IIM与自身免疫性麸质相关疾病CeD、疱疹样皮炎及麸质共济失调之间存在密切的病理生理关联。共同特征包括通过HLA-DQ2.5/-DQ8共享遗传易感性、与疾病活动相关的自身抗体、与炎性细胞浸润的组织病理学相似性以及结构同源转谷氨酰胺酶（TGs）分布相似。在CeD和结缔组织病中报道了具有罕见、一致表型的HLA-DQ2.5限制性麸质特异性CD4 + T细胞。具有相同表型和CDR3β基序的扩增T细胞克隆表明存在持续的、抗原驱动的T细胞反应。
研究表明，CeD肠道适应性免疫反应中的主要成分可能存在于HLA-DQ2.5 + / - DQ8 +的IIM肌肉中。收集到的证据支持这样一种观点，即在一些具有遗传易感性的IIM患者中，麸质可能作为驱动肌炎的外源性抗原。进一步的研究/临床意义：为验证上述假设，需要结合免疫学研究进行临床试验。同时，进行HLA-DQ分型可能是合理的，随后对IIM的HLA-DQ2.5/8 +个体进行小肠活检。
