Heat shock protein expression is low in intestinal mucosa in juvenile idiopathic arthritis: a defect in immunoregulation?
OBJECTIVE
Heat shock proteins (HSPs) are involved in the regulation of inflammation and in the maintenance of mucosal integrity. Their altered expression may be a marker of mucosal inflammation and also contribute to tissue injury. The small intestinal mucosa in children with juvenile idiopathic arthritis (JIA) shows signs of intestinal immune activation, such as increased intraepithelial cytotoxic lymphocyte counts. To further evaluate the characteristics of this immune activation in JIA, we have studied the expression of several HSPs, major histocompatibility complex (MHC) class I-related chain A (MICA), and the heat shock transcription factor 1 (HSF1) in intestinal biopsies from children with JIA.


METHODS
We studied 15 patients with JIA. Controls included 13 children without JIA, studied for various gastrointestinal (GI) symptoms, but eventually shown not to have any GI disease. The subjects were examined by endoscopy. The expression of HSP60, HSP70, MICA, and HSF1 was analysed in ileal and duodenal biopsies by using immunohistochemistry.


RESULTS
The expression levels of HSP60, MICA, and HSF1 were significantly lower in the duodenal epithelium in the JIA patients compared to the controls. MICA and HSF1 also showed lower expression in the ileal epithelium. The expression of HSP70 did not differ between the groups.


CONCLUSIONS
The downregulation of HSP60, MICA, and HSF1 in small intestinal mucosa may indicate that intestinal epithelial cells show immune aberration in JIA. We speculate that the low heat shock response may play a role in the pathogenesis of JIA, interfering with mucosal integrity and local intestinal immunoregulation.
Department of Paediatrics, University of Oulu, and Oulu University Hospital, Oulu, Finland.
M
M
Arvonen
M
M
Tikanmäki
P
P
Vähäsalo
T J
TJ
Karttunen
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology / Q000378:metabolism*; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D004386:Duodenum / Q000276:immunology / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*
D018834:Chaperonin 60; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D014157:Transcription Factors