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- Title
Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus.
- Authors
Hanifi-Moghaddam, P.; Kappler, S.; Seissler, J.; Müller-Scholze, S.; Martin, S.; Roep, B. O.; Strassburger, K.; Kolb, H.; Schloot, N. C.
- Abstract
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.
- Subjects
CHEMOKINES; CYTOKINES; DIABETES; PEOPLE with diabetes; SERUM; AUTOANTIBODIES
- Publication
Diabetic Medicine, 2006, Vol 23, Issue 2, p156
- ISSN
0742-3071
- Publication type
Article
- DOI
10.1111/j.1464-5491.2005.01743.x