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Published on: January 31, 2020
Intestinal immune activation in juvenile idiopathic arthritis and connective tissue disease
J Kokkonen1, M Arvonen, P Vähäsalo
1Department of Paediatrics, University of Oulu, Oulu, Finland.
Insights
Children with juvenile idiopathic arthritis (JIA) or connective tissue disease (CTD) often show gastrointestinal immune system activation. Further research is needed to understand the unknown causes of this reaction.
Area of Science:
- Pediatric Rheumatology
- Gastroenterology
- Immunology
Background:
- Juvenile idiopathic arthritis (JIA) and connective tissue diseases (CTD) can manifest with gastrointestinal (GI) symptoms.
- The prevalence of intestinal immune activation in pediatric patients with JIA/CTD and GI issues is not well-understood.
Purpose of the Study:
- To investigate the occurrence of immune system activation within the GI mucosa of children diagnosed with JIA or CTD.
- To compare immune cell populations and histological findings in the GI tract between JIA/CTD patients and a control group.
Main Methods:
- A cohort of 27 children with JIA/CTD and GI symptoms was compared to 54 healthy children with GI symptoms.
- Gastroduodenoscopy and colonoscopy were performed, with biopsies analyzed for intraepithelial lymphocyte populations (CD3+, alpha/beta+, gamma/delta+) and lymphoid nodular hyperplasia (LNH).
Main Results:
- Lymphoid nodular hyperplasia (LNH) was significantly more prevalent in JIA/CTD patients (74%) compared to controls (16%).
- Increased counts of CD3+, alpha/beta+, and gamma/delta+ lymphocytes were observed in the duodenum of JIA/CTD patients.
- Elevated gamma/delta+ cell numbers were found in the ileum of JIA/CTD patients, with 89% of patients showing LNH, increased gamma/delta+ cells, or both, versus 13% of controls.
Conclusions:
- A majority of children with JIA or CTD experiencing GI symptoms exhibit signs of intestinal immune system activation.
- The underlying cause of this immune activation is currently unknown, though it shares similarities with reactions seen in delayed-type food allergies.
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.
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