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.
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.
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Tanja
0000-0001-7300-916X
T
Milicic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Aleksandra
0000-0002-7997-9076
A
Jotic
Institute for Biochemistry, Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
Ivanka
I
Markovic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Katarina
0000-0002-8070-1899
K
Lalic
Department for Operations Research and Statistics, Faculty of Organizational Sciences, University of Belgrade, Jove Ilica 154, Belgrade, Serbia.
Veljko
0000-0002-7761-1841
V
Jeremic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Ljiljana
L
Lukic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Natasa
N
Rajkovic
Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
Dušan
D
Popadic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Marija
M
Macesic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Jelena P
JP
Seferovic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Sandra
0000-0001-9255-1392
S
Aleksic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Jelena
J
Stanarcic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Milorad
M
Civcic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.
Nebojsa M
NM
Lalic