Recognition of heat shock protein 60 epitopes in children with type 1 diabetes

Abstract

Background Treatment with a specific HSP60 epitope in new onset of type 1 diabetes (T1D) patients has been shown to preserve endogenous insulin production. Previously, recognition of pan HLA‐DR‐binding HSP60 epitopes in various autoimmune diseases was found; this study investigated recognition of these epitopes in newly diagnosed T1D patients and correlated findings to the occurrence of a partial remission. Methods Peripheral blood mononuclear cells of 18 children with T1D were prospectively collected at disease onset and a few months after diagnosis. Epitope‐specific T‐cell proliferation and cytokine production (intracellular and in culture supernatants) were measured. Results were compared with 31 longstanding T1D patients and ten healthy controls. Results Although HSP60 epitope‐specific T‐cell proliferative responses were detected, overall proliferative responses were low. At onset, epitope‐specific intracellular IFN‐γ production was higher in T1D patients compared with healthy controls (p < 0.05). At follow‐up, both IL‐10 and IFN‐γ production were higher in those without a partial remission than in those with a partial remission (both p < 0.05). Also, IL‐10 and IFN‐γ production were higher compared with onset for patients without a PR (both p < 0.01). In supernatants of HSP60 epitope‐specific T‐cell cultures, no substantial differences in cytokine production were found between T1D patients with and without a partial remission, either at onset or a few months after onset. As patient numbers were small, results should be interpreted with caution. Conclusions Pan‐DR‐binding HSP60 peptides induced low peptide‐specific proliferative responses and peptide‐specific production of some, mainly intracellular, cytokines in T1D patients. Recognition did not differ significantly between patient groups and various time points. Copyright © 2012 John Wiley & Sons, Ltd.

Does Hsp60 Provide a Link between Mitochondrial Stress and Inflammation in Diabetes Mellitus?

“…Various studies with human patients have shown that treatment of Type 1 diabetes with p277 epitope can preserve part of the endogenous insulin production by arresting the destruction of the β -cell mass in the pancreas [ 25 , 26 ]. The paper by Stuart et al, 2012, states that a number of Hsp60 peptide epitopes that can bind multiple allelic variants of the human major histocompatibility complex molecule HLA-DR are called pan-DR epitopes which can induce low peptide-specific proliferative responses and peptide-specific production of intracellular cytokines such as interleukin-10 (IL-10), an anti-inflammatory cytokine, and interferon- γ (IFN- γ ) in Type 1 diabetes [ 26 ]. This suggests that Hsp60 and peptides derived from the full-length molecule can induce both proinflammatory and anti-inflammatory cytokines.…”

The Role of Heat Shock Proteins in Type 1 Diabetes

“…The research to date on HSPs in the field of diabetes has limitations. A study reporting T-cell proliferative responses and HSP60-derived epitope-specific cytokine production should be interpreted with caution as patient numbers were small ( 111 ). Genetic polymorphism in HSP genes also present a confounding factor for interpretation of both pre-clinical and clinical data in HSPs-T1D studies.…”