High risk first degree relatives of type 1 diabetics: An association with increases in CXCR3+ T memory cells reflecting an enhanced activity of Th1 autoimmune response

Tanja Milicic, Aleksandra Jotic, Ivanka Markovic, Katarina Lalic, Veljko Jeremic, Ljiljana Lukic, Natasa Rajkovic, Dušan Popadic, Marija Macesic, Jelena P. Seferovic, Sandra Aleksic, Jelena Stanarcic, Milorad Civcic, Nebojsa M. Lalic

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We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA-, IA-2-)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P < 0.001). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P < 0.05). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response.

Original languageEnglish (US)
Article number589360
JournalInternational Journal of Endocrinology
Publication statusPublished - 2014
Externally publishedYes


ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems

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