Intestinal immune activation in juvenile idiopathic arthritis and connective tissue disease

Objectives: To examine the prevalence of immune activation in gastrointestinal ( GI) mucosa in children with juvenile idiopathic arthritis ( JIA) or connective tissue disease ( CTD). Study design: We studied 27 children ( 15 girls, mean age 9.8 +/- 4.8 years) with JIA/ CTD and GI symptoms, including nine with oligoarthritis, nine with polyarthritis, two with systemic arthritis, three with enthesitis-related arthritis, and four with various CTDs. The control group consists of 54 children ( 31 girls, mean age 11.3 +/- 6.3 years) with GI symptoms but shown to have no significant GI or rheumatoid disorder. The subjects were examined by gastroduodenoscopy ( 22 patients, 50 controls) and colonoscopy ( 23 patients, 16 controls). Intraepithelial CD3(+), alpha/beta(+), and gamma/delta(+) lymphocytes were counted from duodenal and ileal biopsies. Results: Five patients with JIA/ CTD ( 19%) had ulcerative colitis. Lymphoid nodular hyperplasia ( LNH) was more common in the patients [ 74% ( 20/ 27)] than in the controls [ 16% ( 8/ 50), p=0.001], as well in the duodenal bulb [ 29% ( 7/ 24) vs. 10% ( 5/ 50)], terminal ileum [ 74% ( 14/ 19) vs. 38% ( 5/ 13)], and the colon [ 50% ( 11/ 22) vs. 14% ( 2/ 14)]. In the duodenum, CD3, alpha/beta(+), and gamma/delta(+) lymphocytes counts were higher in JIA/ CTD ( p < 0.05). In the ileum, gamma/delta(+) cell numbers had increased in JIA/ CTD ( p < 0.05). Either LNH, increased gamma/delta(+) count, or both were more common in JIA/ CTD [ 89% ( 24/ 27)] than in the controls [ 13% ( 7/ 54), p < 0.0001]. Conclusions: The majority of children suffering from JIA or CTD with GI symptoms show abnormalities consistent with activation of the intestinal immune system. The aetiology of this reaction remains unknown, but similar features are seen in delayed- type food allergy.