The gut-joint axis: cross-reactive food antibodies in rheumatoid arthritis

Mette Hvatum ¹, Lars Kanerud ², Roger Hällgren ³ and Per Brandtzaeg ^1*

¹ LIIPAT, Institute of Pathology, University of Oslo, Norway
² Department of Rheumatology, Södersjukhuset Stockholm, Sweden
³ Department of Internal Medicine, University Hospital, Uppsala, Sweden

^* To whom correspondence should be addressed. E-mail: per.brandtzaeg{at}medisin.uio.no.

Accepted 1 February 2006

Abstract

Background: Patients with rheumatoid arthritis (RA) often feel an association between food intake and their disease severity.

Methods: To substantiate immunologically a connection between RA and intestinal immunity, we measured IgG, IgA, and IgM antibodies to dietary antigens in serum and jejunal perfusion fluid from 17 RA patients and 20 healthy subjects. The antigens originated from cow's milk (-lactalbumin, -lactoglobulin, casein), cereals, hen's egg (ovalbumin), cod fish, and pork meat.

Results: In intestinal fluid of many RA patients, all three Ig classes showed elevated food-specific activities. Except for IgM activity against - lactoglobulin, all other IgM activities were highly significantly increased unrelated to the elevation of total IgM. The RA-associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently elevated, with no significant increase against gliadin and casein. Considerable cross-reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalized after treatment but clinical improvement was rather reflected in a reduced erythrocyte sedimentation rate.

Conclusion: The production of cross-reactive antibodies is strikingly elevated in the gut of many RA patients. Their food-related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.

Keywords: food antibodies, inflammation, intestinal mucosa, rheumatoid arthritis

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