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

M Hvatum^1,

¹ Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway
² Department of Rheumatology, Karolinska Institute, Stockholm Söder Hospital, Stockholm (current address: Rheumatology Unit, Karolinska Institute, Farsta Läkarhus, Farsta), Sweden
³ Department of Medical Sciences, University Hospital, Uppsala, Sweden

Correspondence to:
Correspondence to:
Professor P Brandtzaeg
Institute of Pathology, Rikshospitalet, N-0027 Oslo, Norway; per.brandtzaeg{at}medisin.uio.no

ABSTRACT
Background and aims: Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response.

Methods: IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow’s milk (-lactalbumin, ß-lactoglobulin, casein), cereals, hen’s egg (ovalbumin), cod fish, and pork meat.

Results: In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against ß-lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, 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 normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate.

Conclusions: The production of cross reactive antibodies is strikingly increased 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.

Abbreviations: RA, rheumatoid arthritis; RF, rheumatoid factor; NSAID, non-steroidal anti-inflammatory drug; ELISA, enzyme linked immunosorbent assay; BSA, bovine serum albumin; OD, optical density; SIgA, secretory IgA

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

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