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2000
Volume 19, Issue 2
  • ISSN: 2772-2708
  • E-ISSN: 2772-2716
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Abstract

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.

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.

© 2025 The Author(s). Published by Bentham Science Publisher.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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Inflammatory Myopathies and Autoimmune Gluten-related Disorders: A Scoping Review of Pathophysiological Interconnections and Hypothesis
Rec Adv Inflamm Allergy Drug Discov 19, 221 (2025); https://doi.org/10.2174/0127722708317244240919113305
/content/journals/raiad/10.2174/0127722708317244240919113305
/content/journals/raiad/10.2174/0127722708317244240919113305
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  • Article Type:     Review Article
Keyword(s): autoimmunity; environmental risk factors; extraintestinal manifestations; gluten-related autoimmune disorders; Idiopathic inflammatory myopathies; pathophysiology

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