[Exploration of CCL11 and sTNFR2 as potential biomarkers for the efficacy of lymphocyte immunotherapy in women with unexplained recurrent spontaneous abortion].

Abstract

Objective: To explore biomarkers for the efficacy of lymphocyte immunotherapy (LIT) treating women with unexplained recurrent spontaneous abortion (URSA). Methods: Serum samples from 24 URSA potients who received LIT were collected at Peking University Third Hospital from December 2014 to June 2015. Semiquantitative sandwich-based antibody arrays containing 40 cytokines were used to screen target immune cytokines in the peripheral blood of URSA patients before and after LIT. Multifactor quantitative microsphere flow cytometry detection validated the levels of target cytokines. Based on the final pregnancy outcome after LIT, 24 URSA patients were divided into the full-term delivery group (15 cases) and the abortion group (9 cases). Furthermore, linear regression analysis were applied to evaluate the relationship between target cytokines and pregnancy outcomes. Results: Semiquantitative sandwich-based antibody arrays suggested that, among all 24 URSA patients included in this study, the intensities of the fluorescence signal were significantly lower post-LIT versus pre-LIT for the following cytokines: interleukin-15 (IL-15), monokine induced by γ-interferon (MIG), C-C motif chemokine ligand (CCL) 1 (all P<0.05). In the full-term delivery group, the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines: IL-15, CCL1, macrophage inflammatory protein (MIP) 1α (all P<0.05). In the abortion group, the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines: MIG, MIP-1δ (all P<0.05). Linear regression analysis showed that the intensity of the fluorescence signal of CCL11 was increased and the intensity of the fluorescence signal of soluble tumor necrosis factor receptor 2 (sTNFR2) was decreased in the full-term delivery group after LIT, the differences were statistically significant (P=0.012, 0.029). Validation results of multifactor quantitative microsphere flow cytometry detection showed that the level of CCL11 was significantly increased (P=0.001) and the level of sTNFR2 was significantly decreased (P=0.001) in the full-term delivery group after LIT. Conclusion: CCL11 and sTNFR2 maybe serve as potential biomarkers that could predict pregnancy outcomes after LIT in women with URSA.