CD4+ T cell responses to epitopes of self-heat shock protein 70 in patients with juvenile dermatomyositis. (22nd February 2011)

• Record Type: Journal Article
• Authors: Koffeman, EC; Elst, EF; van Wijk, F; Prakken, B; van Royen-Kerkhof, A
• Is Part Of: Annals of the rheumatic diseases. Volume 70(2011)Supplement 2
• Page Start: A44
• Page End: A45
• Publication Date: 2011-02-22
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2010.148981.6
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background and objectives: Juvenile dermatomyositis (JDM) is a childhood disease characterised by inflammation in the muscle and the skin. In several human chronic inflammatory diseases CD4 T cell responses to epitopes of heat shock proteins (hsp) have been found to play a role, both pathogenic and regulatory. In JDM hsp70 is highly up regulated in the inflamed muscle. Therefore, hsp70 could be a target in the inflammatory process in JDM. Responses to hsp70 epitopes in JDM have not yet been characterised. In HLA elution studies it has become clear that epitopes from self-hsp70 are abundantly bound to HLA. In this study the authors tested whether peripheral blood CD4 T cell responses to hsp70-epitopes can be detected and whether they are different in JDM patients compared to healthy controls (HC). Materials and methods: Hsp70-epitopes were selected based on (1) literature on HLA-elution studies, (2) HLA-class II binding capacity tested with computer models and (3) in vitro responses by CD4 T cells from healthy donors. Proliferation of PBMC from healthy controls (HC, age 2–18) and JDM patients and juvenile idiopathic arthritis patients as disease controls was tested using 3H-thymidine assays and CFSE-staining. Cytokine production was tested by Luminex analysis, flow cytometry and PCR. Results: The following epitopes were selected: aa 38–52, aa 161–175, aa 290–304 and aa 443–457. These peptides were immunogenic in humans, inducing proliferation or cytokine production. The proliferation of CD4 T cells towards aa 443–457 is increased in JDM. Conclusion: The authors identified novel epitopes of hsp70 that are immunogenic in healthy donors and JDM and they found indications that the CD4 T cell response towards H443 is increased in JDM.