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

Abstract

We analyzed the level of (a)CXCR3(+) (Th1) and CCR4(+) (Th2) T memory cells (b) interferon-gamma. 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 LT 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 LT 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.