Human intestinal flora and the induction of chronic arthritis : studies in an animal model.

The etiology of rheumatoid arthritis (RA), a chronic joint inflammation, is unknown. A microbial involvement is suspected, but no particular microorganism has been incriminated. The human intestinal microflora is an abundant and continuous source of bacterial antigens and may be involved in the induction or maintenance of chronic joint inflammation. In this introductory chapter I shall describe the possible relationship between joint inflammation, bowel flora and intestinal disease. Clinical syndromes which suggest this relationship are presented. Characteristics of the human intestinal flora are described, together with bacterial cell wall structures and their immunological properties. Several aspects of the hypothesis that intestinal bacterial antigens may pass the intestinal wall and give rise to inflammatory symptoms at distant locations are discussed. Animal models developed to study joint inflammation, including two models which use bacterial antigens to elicit arthritis, are presented. Finally, the experimental work of this thesis is introduced

Arthritis by autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments

__Abstract__ T cell lines (B13, B19) were isolated from the lymph nodes of Lewis rats 12 days after an arthritogenic injection of cell wall fragments of Eubacterium aerofaciens (ECW), a major resident of the human intestinal flora. These cell wall fragments consist of peptidoglycan polysaccharide complexes (PPC). The cell lines that bear the helper phenotype were arthritogenic in knee or ankle joints upon intravenous injection into irradiated Lewis recipients. B13 was, however, not arthritogenic in irradiated F344 recipients that are largely RT1 identical. The arthritis induced in the knee joints of the irradiated Lewis rats was clearly shown by a 99mtechnetium-pertechnetate scanning technique and was confirmed histologically. In vitro the cell lines showed a proliferative response after stimulation with syngeneic spleen cells alone. The proliferation was significantly higher when bacterial PPC, isolated in soluble form from normal feces or ileostomy fluid were added. Recognition by B13 appeared to be MHC class II restricted. These results show that autoreactive T cell lines can be isolated from rats after injection of bacterial cell wall antigens and that these cell lines can be arthritogenic. This suggests a role for autoreactive T cells in the induction of bacterial cell wall arthritis and might give a clue for the arthritogenic properties of the normal human intestinal flora

PRKAR1B mutation associated with a new neurodegenerative disorder with unique pathology

Genetics of disease, diagnosis and treatmen

Social position of adolescents with chronic digestive disorders

Objective: To investigate the consequences of having a chronic digestive disorder on the social position of adolescents. Methods: Five diagnostic groups, including inflammatory bowel disease (IBD), chronic liver diseases, congenital digestive disorders, coeliac disease and food allergy (total n = 758, ages 12-25 years), were each compared with a population-based control group in a multicentre study using a cross-sectional design. Social position was assessed by a mailed questionnaire measuring 24 aspects, categorized as education, leisure activities, friendship, labour participation, financial situation, partnership and sexuality. Results: Eight aspects of social position were found to be affected negatively by one or more chronic digestive diseases: absence from school due to illness, going out, having a paid job, needing re-education in order to get a job, getting benefits as main income source, encountering bottlenecks in establishing financial commitments, having self-confidence in making a pass at someone, and restrictions in making love. Adolescents with chronic liver disease and IBD were found to experience more restrictions in social position. Adolescents with food allergy and congenital digestive disorders appear to experience some restrictions, but to a lesser degree, and adolescents with coeliac disease do not appear to have any problems regarding social position compared with controls. Conclusion: The social position of adolescents is affected negatively by having a chronic digestive disease, in particular chronic liver disease and IBD. Negative consequences occur in education, leisure activities, labour participation, financial situation, partnership and sexuality