title: Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus.
abstract: OBJECTIVE
  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.
  
  
  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-gamma, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hanifi-Moghaddam
authors.forename: S
authors.initials: S
authors.lastname: Kappler
authors.forename: J
authors.initials: J
authors.lastname: Seissler
authors.forename: S
authors.initials: S
authors.lastname: Müller-Scholze
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: K
authors.initials: K
authors.lastname: Strassburger
authors.forename: H
authors.initials: H
authors.lastname: Kolb
authors.forename: N C
authors.initials: NC
authors.lastname: Schloot
mesh_terms: D001323:Autoantibodies / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000097:blood*; D019742:Chemokines, CC / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007515:Islets of Langerhans / Q000737:chemistry; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; C111835:CCL2 protein, human; C066507:CCL4 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D018793:Interleukin-13; D020382:Interleukin-18; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma