The correlation between T helper 17 cell/regulatory T cell imbalance and cytokines in patients with immunoglobulin G4-related disease / 中华风湿病学杂志

ABSTRACT

Objective:To investigate the characteristics of lymphocyte subsets in peripheral blood of patients with immunoglobulin G4-related disease (IgG4-RD) and the correlation between T helper 17 cell (Th17)/regulatory T cells (Treg) cell imbalance and cytokines.Methods:A total of 31 patients with IgG4-RD who were admitted to the Rheumatology and Immunology Department of the Second Hospital of Shanxi Medical University from January 2016 to June 2020 were included. We collected their clinical and laboratory data, and selected 30 age and sex matched healthy people as the control group. Flow cytometry was used to detect the percentage and absolute number of lymphocyte subsets [T, B, natural killer cell (NK), CD4 +T, CD8 +T] and CD4 +T subsets [Th1, Th2, Th17, CD4 +CD25 +forkhead box protein 3 (Foxp3) +Treg] in peripheral blood of IgG4-RD patients and healthy controls. The serum interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ levels in the IgG4-RD patients were measured by cytometric bead array (CBA). Correlation between Th17/Treg ratio and disease-related indicators was also analyzed. We used χ2 test, Mann-Whitney U test and Spearman correlation analysis for statistical analysis. Results:① The percentage of CD4 +T cells in the peripheral blood of IgG4-RD patients was higher than that of healthy controls [45.00%(33.97%, 51.48%) vs 39.36%(33.78%, 43.30%), Z=-2.142, P<0.05]. ② The percentage and absolute number of Th17 cells was increased in IgG4-RD patients [1.13%(0.70%, 1.55%) vs 0.77%(0.43%, 1.07%), Z=-2.229, P<0.05; 7.90(5.20, 12.23) cells/μl vs 5.60(3.12, 8.47) cells/μl, Z=-2.568, P<0.05], while the percentage of Treg cells was decreased [3.37%(2.82%, 5.65%) vs 4.96%(4.18%, 6.34%), Z=-2.986, P<0.01]. But the number of Treg cells showed no difference between the two groups. ③ Th17/Treg ratio was significantly increased in IgG4-RD patients [0.29(0.16, 0.46) vs 0.15(0.08, 0.23), Z=-3.119, P<0.01], and it was positively correlated with IgG4-RD response index score ( r=0.491, P<0.01). ④ Serum IL-6 [13.72(9.29, 26.06) pg/ml vs 2.23(1.94, 3.10) pg/ml, Z=-4.815, P<0.01], IL-10 [5.46(4.28, 15.38) pg/ml vs 1.81(1.59, 2.02) pg/ml, Z=-5.298, P<0.01], TNF-α [4.25(1.47, 7.26) pg/ml vs 1.15(1.05, 1.45) pg/ml, Z=-3.146, P<0.01] and IFN-γ [3.89(1.76, 6.61) pg/ml vs 1.41(1.24, 1.65) pg/ml, Z=-3.172, P<0.01] in IgG4-RD group were significantly higher than those in healthy control group. Moreover, Th17/Treg ratio was negatively correlated with IL-2 level ( r=-0.554, P<0.05). Conclusion:Th17/Treg disorder exists in IgG4-RD patients, and it is related to disease activity, indicating that Th17/Treg imbalance may be an important mechanism in IgG4-RD. IL-2 plays an important role in regulating Th17/Treg balance and may be a potential immunotherapy target in future.