Elevated serum IP-10 levels observed in type 1 diabetes.
OBJECTIVE
Although most patients with type 1 diabetes are considered to have T-cell-mediated autoimmune disease, a method of measuring of pancreatic beta-cell-specific T-cell function in cases of type 1 diabetes has yet to be established. Here, we focused on interferon-inducible protein-10 (IP-10), a chemokine that promotes the migration of activated T-helper 1 (Th1) cells and measured serum IP-10 levels in patients with human type 1 diabetes, which is regarded as a Th1-mediated disease.


METHODS
Serum samples were obtained from diabetic patients, and the levels of autoantibodies (GAD and insulinoma-associated protein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive for either or both of the autoantibodies were classified as Ab+ type 1, and those negative for both were classified as Ab type 1. To evaluate islet antigen-specific responses, peripheral blood from patients stimulated with or without GAD was used, and intracellular cytokine staining for flowcytometry was performed.


RESULTS
The Ab+ and Ab- type 1 groups both showed a significantly higher serum IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, respectively), and the IP-10 level in the recent-onset Ab+ subgroup was significantly higher than that in the established (longstanding) Ab+ subgroup (P < 0.002). Furthermore, there was a significant positive correlation between the serum IP-10 level and the number of GAD-reactive gamma-interferon-producing CD4+ cells in the Ab+ type 1 group (P < 0.007).


CONCLUSIONS
Our findings demonstrate that measurement of serum IP-10 concentrations is useful in patients with type 1 diabetes.
Shimada
A
A
Division of Endocrinology, Keio University School of Medicine, Tokyo, Japan. asmd@med.keio.ac.jp
Morimoto
J
J
Kodama
K
K
Suzuki
R
R
Oikawa
Y
Y
Funae
O
O
Kasuga
A
A
Saruta
T
T
Narumi
S
S
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007527:Isoenzymes / Q000276:immunology; D007564:Japan; D008297:Male; D012016:Reference Values
D001323:Autoantibodies; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C096322:ICA512 autoantibody; D007527:Isoenzymes; D007371:Interferon-gamma; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2