Heat shock protein-derived T-cell epitopes contribute to autoimmune inflammation in pediatric Crohn's disease.

Pediatric Crohn's disease is a chronic auto inflammatory bowel disorder affecting children under the age of 17 years. A putative etiopathogenesis of Crohn's disease (CD) is associated with disregulation of immune response to antigens commonly present in the gut microenvironment. Heat shock proteins (HSP) have been identified as ubiquitous antigens with the ability to modulate inflammatory responses associated with several autoimmune diseases. The present study tested the contribution of immune responses to HSP in the amplification of autoimmune inflammation in chronically inflamed mucosa of pediatric CD patients. Colonic biopsies obtained from normal and CD mucosa were stimulated with pairs of Pan HLA-DR binder HSP60-derived peptides (human/bacterial homologues). The modulation of RNA and protein levels of induced proinflammatory cytokines were measured. We identified two epitopes capable of sustaining proinflammatory responses, specifically TNF< and IFN induction, in the inflamed intestinal mucosa in CD patients. The responses correlated positively with clinical and histological measurements of disease activity, thus suggesting a contribution of immune responses to HSP in pediatric CD site-specific mucosal inflammation.

Aerobic exercise capacity in patients with juvenile dermatomyositis.

OBJECTIVE: To examine the feasibility of maximum exercise testing in patients with juvenile dermatomyositis (JDM), characterize the maximum oxygen consumption (VO2peak) of these patients, and determine if exercise time could be used as an surrogate index for VO2peak. METHODS: Fifteen patients diagnosed with JDM (age 5-14) performed a graded, maximum exercise test using a motor driven treadmill and metabolic cart to volitional exhaustion conforming to the Bruce protocol. RESULTS: All patients were able to perform the exercise test. Ten of the 15 patients performed a maximal effort (heart rate > 180 beats/min or respiratory exchange ratio > 1.0). The patients who had a maximal exercise performance, the mean absolute VO2peak, relative VO2peak (related to body mass), and exercise time were respectively -1.82 (+/- 1.5), -2.83 (+/- 1.9), and -3.65 (+/- 1.9) standard deviations lower compared to age and sex matched reference values (p < 0.05). Z scores for exercise time were significantly lower compared to Z scores for absolute and relative VO2peak, an indication of reduced muscular economy. When exercise time was converted to VO2peak using the equation: VO2peak = 0.1583 (exercise time) + 0.0828, the VO2peak values were not significantly different from the measured VO2peak values. CONCLUSION: Aerobic exercise testing on a treadmill was possible in patients with JDM and revealed an impairment in their maximal aerobic exercise capacity. Exercise time can be used as an indicator of VO2peak, when converted to VO2peak using a regression equation. VO2peak, measured or estimated, has the potential to be a good indicator of muscle function in patients with JDM.