Article
Rheumatoid arthritis–celiac disease are related: The gut feeling of the joints
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Published: | August 29, 2016 |
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Background: Rheumatoid arthritis (RA) and celiac disease (CD) belong to the autoimmune disease family. Despite being separate entities they share aspects. The objectives were to compare these for epidemiological, clinical, pathophysiological, diagnostic serology and genetic aspects.
Medline, Google, and Cochrane Library databases were reviewed to identify publications of the last 35 years on RA and CD on above mentioned aspects.
Methods: Epidemiologically they share comparable incidences, environmental influences, associated antibodies and a recent incidental surge. They differ in HLA pre-dispositions and specific predictive/diagnostic biomarkers. At clinical level, CD exhibits extra-intestinal rheumatic and RA gastrointestinal manifestations. Small bowel pathology precede joint manifestations of rheumatic patients.
A trend towards responsiveness to a gluten free diet has been observed, ameliorating celiac rheumatic manifestations, whereas dietary interventions for RA remain controversial.
Results: Pathophysiologically, both diseases are mediated by endogenous enzymes in target organs. Peptidylargenine deiminase and tissue transglutaminase are active in the intestine and joints, respectively. The infectious, enzymatic dysbiotic post translational modification of proteins and increased intestinal permeability theories, as drivers of the autoimmune cascade, apply to both diseases.
Conclusion: Contrary to their specific HLA pre-disposition, the diseases share multiple non-HLA loci. Those genes are crucial for activation and regulation of adaptive and innate immunity. Recently, light was shed on the interaction between host genetics and microbiota composition in relation to CD and RA susceptibility, connecting bugs and us and autoimmunity.
A better understanding of the above mentioned similarities in the gut–joint inter-relationship, may elucidate additional facets in the mosaic of autoimmunity, relating CD to RA.