Rheumatoid arthritis–celiac disease relationship: Joints get that gut feeling

• Inflammation and autoimmunity reside in the intestinal mucosa, years prior to the onset of detectable joint inflammation.
• RA and CD share clinical, epidemiological, serologic, environmental, genetic, dysbiotic and gut permeability manifestations.
• The intestine have all the necessary tools to produce neo-epitopes, initiating autoimmunity and autoantibody generation in RA.
• Exploring the intestinal routs of RA can lead to intestinal-targeted strategies to prevent, early diagnose or treat RA.

Rheumatoid arthritis (RA) and celiac disease (CD) belong to the autoimmune disease family. Despite being separate entities they share multiple aspects. Epidemiologically they share comparable incidence environmental influences, associated antibodies and a recent incidental surge. They differ in their HLA pre-dispositions and specific predictive and diagnostic biomarkers. At the clinical level, celiac disease exhibits extra-intestinal rheumatic manifestations and RA gastrointestinal ones. Small bowel pathology exists in rheumatic patients. A trend towards responsiveness to a gluten free diet has been observed, ameliorating celiac rheumatic manifestations, whereas dietary interventions for rheumatoid arthritis remain controversial.Pathophysiologically, both diseases are mediated by endogenous enzymes in the target organs. The infectious, dysbiotic and increased intestinal permeability theories, as drivers of the autoimmune cascade, apply to both diseases.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.