Inflammatory myopathies and autoimmune gluten-related disorders

Despite modern medical therapies, multiorgan idiopathic inflammatory myopathies (IIM) are associated with reduced quality of life and life expectancy. A systematic review of all published peer-reviewed case reports of patients with concurrent IIM and celiac disease uncovered patients in whom the introduction of a gluten-free diet led to dramatic improvement of myositis. The collected evidence was suggestive of associations between myositis disease activity and gluten exposure.

To follow up on these findings, a scoping review, “Inflammatory myopathies and autoimmune gluten-related disorders: Scoping review of pathophysiological interconnections and hypothesis”, has now been published. It presents for the first time the available evidence on basic pathophysiological interconnections between IIM and the autoimmune gluten-related disorders of celiac disease, dermatitis herpetiformis, and gluten ataxia.

Among the several common traits described are a shared genetic predisposition through HLA-DQ2.5/-DQ8, disease activity-associated autoantibodies, and histopathological parallels with inflammatory cell infiltrates and structural homologous transglutaminase enzymes with what appears to be parallel distribution within diseased tissue. HLA-DQ2.5-restricted gluten-specific CD4+ T cells of a rare, uniform phenotype have been reported in CeD and connective tissue disease, and the presence of expanded T-cell clones with identical phenotypes and CDR3β motifs indicate the presence of a continuous, antigen-driven T-cell response in the inflammatory myopathies as well as the autoimmune gluten-related disorders.

The investigations and collected literature revealed that the major components involved in the adaptive immune response in the gut in celiac disease, have also been reported in muscle in HLA-DQ2.5+/-DQ8+ patients with IIM. The findings support a novel hypothesis, outlined in the article: that in some genetically predisposed patients with IIM, gluten may act as an exogenous antigen driving myositis, perhaps via direct effects in non-gastrointestinal tissue.

The findings may open for new insights into how gluten as exogenous antigen may affect bodily tissues outside the gut. The article suggests ways to move research in this field forward through clinical trials and immunological studies.

Implications for clinical practice

Case reports describe how some patients suffering from the burdens of inflammatory myopathy experienced partial or full long-term recovery after the diagnosis of concomitant celiac disease and the subsequent start of a gluten-free diet, some with a gluten-free diet as their only treatment thereafter. More studies are needed before an estimate can be given on whether such HLA-restricted gluten-sensitive myositis are rare occurrences or whether this affects a larger proportion of patients with IIM. Meanwhile, the inclusion of HLA-DQ typing as part of the workup in these patients may be justified, and in HLA-DQ2.5/8+ patients with IIM, subsequent small-intestinal biopsies may be considered. Current research suggests that patients with IIM who are diagnosed with celiac disease should be encouraged to follow a strict gluten-free diet.

This article is based on a press release from Bentham Science Publishers.