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Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus
Author(s) -
HanifiMoghaddam P.,
Kappler S.,
Seissler J.,
MüllerScholze S.,
Martin S.,
Roep B. O.,
Strassburger K.,
Kolb H.,
Schloot N. C.
Publication year - 2006
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2005.01743.x
Subject(s) - medicine , chemokine , autoantibody , diabetes mellitus , ccl3 , immunology , ccl5 , type 1 diabetes , islet , endocrinology , antibody , immune system , ccl2 , t cell , il 2 receptor
Aims The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines. Subjects and methods Forty‐two non‐diabetic first‐degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA‐2 antibody). Follow‐up for 9–11 years confirmed high vs. moderate diabetes risk in islet autoantibody‐positive vs. ‐negative relatives. Cytokines and chemokines were determined by enzyme‐linked immunosorbent assay (ELISA). Results Serum concentrations of classic Th1‐associated cytokines (IFN‐γ, IL‐12, IL‐18) or Th2/Treg‐associated cytokines (IL‐5, IL‐10, IL‐13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased ( P = 0.0442 and P = 0.0334) while CCL2 was decreased ( P = 0.0318) in the multiple islet autoantibody‐positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk ( r = 0.84, P = 0.00005), but not in the autoantibody‐negative group. Conclusion Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up‐regulation of CCL3 and CCL4 vs. down‐regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.