Associations of Th1, Th2, Th17, and Treg cell levels and imbalance with recurrent spontaneous abortion: A meta-analysis

Objective: Abnormal levels and imbalances of T cell subsets are common in recurrent spontaneous abortion (RSA) patients, but most studies have small sample sizes, and comprehensive evaluations are lacking. Therefore, this meta-analysis aimed to comprehensively investigate T cell subsets and their ratios in RSA patients.

Methods: Four databases (PubMed, EMBASE, Web of Science, and Cochrane Library databases) were searched until 10 January 2024. T helper 1 (Th1), Th2, Th1/Th2 ratio, Th17, regulatory T (Treg), Treg/Th17 ratio, and the correlation between Th17 and Treg were considered endpoint indexes.

Results: Twenty-six studies involving 1143 RSA women (RSA group) and 863 healthy women (healthy control group) were included. Th1 (standardized mean difference [SMD] = 0.603%; 95% confidence intervals [CI]: 0.406%, 0.800%; p < 0.001), Th1/Th2 ratio (SMD = 0.838; 95% CI: 0.364, 1.312; p = 0.001), and Th17 (SMD = 1.047%; 95% CI: 0.734%, 1.360%; p < 0.001) increased; Th2 (SMD = -0.719%; 95% CI: -1.263%, -0.174%; p = 0.010), Treg (SMD = -1.176%; 95% CI: -1.755%, -0.596%; p < 0.001) and Treg/Th17 ratio (SMD = -0.978; 95% CI: -1.576, -0.381; p = 0.001) reduced in RSA group versus healthy control group. Th17 were inversely correlated with Treg in RSA patients (Correlation coefficient = -0.488; 95% CI: -0.726, -0.145; p = 0.019). The risk of bias was relatively low. There was no publication bias for Th1, Th2, or Th1/Th2 ratio; publication biases for other outcomes were corrected by the trim-and-fill method. Sensitivity analyses showed relatively high robustness.

Conclusion: Th1, Th1/Th2 ratio, and Th17 are elevated, while Th2, Treg, and Treg/Th17 ratio are reduced in RSA patients. Meanwhile, Th17 was inversely correlated with Treg in these patients.