Expression And Clinical Significance Of CD28 Family Costimulatory Molecules In Decidua Of Patients With Unexplained Recurrent Spontaneous Abortion

Objective:To detect the expression of CD28,CTLA-4,ICOS and PD-1 in decidual tissues of patients with unexplained recurrent spontaneous abortion,and investigate the correlation between the expression of costimulatory molecules in CD28 family in the maternal fetal interface and unexplained recurrent spontaneous abortion.Methods:1.20 patients with unexplained recurrent spontaneous abortion and 20 normal pregnant women were recruited and their decidual tissues were collected on the basis of voluntary principle.2.The infiltration of inflammatory cells in decidual tissue was observed by routine HE staining.The levels of CD28,CTLA-4,ICOS and PD-1 mRNA in decidual tissues were detected by RT-PCR.Flow cytometry was used to detect the expression levels of CD28,CTLA-4,ICOS and PD-1 on the CD3+ T cells in decidual tissue.The correlation between the expression levels of these costimulatory molecules and unexplained recurrent spontaneous abortion were evaluated.Results:1.A significant increase in inflammatory cell infiltration of decidual tissue in the URSA group.Compared with the normal pregnant women,there was no significant difference between the URSA group of CD28 in decidual tissue mRNA level(8.51×10-6±4.97×10-6 vs 6.82×10-6±3.02×10-6,P>0.05),CTLA-4 mRNA(2.35×10-4± 1.17×10-4 vs 2.09×10-5±0.79×10-5,P<0.05)level was significantly increased;the ratio of CD28/CTLA-4(0.036±0.049 vs 0.48±0.55,P<0.05)was significantly decreased.Flow cytometry assay showed that compared with the normal pregnant women,no significant difference was found in the proportion of CD3+CD28+T cell subsets(65.0±7.15% vs 59.2±4.51%,P>0.05)in patients with URSA,but the CD3+ CTLA-4+subgroup of T cells was increased significantly(4.54 ±3.95% vs 2.11 ±1.57%,P<0.05).2.Compared with the normal pregnant women,decidual tissue in group URSA ICOS mRNA(1.17×10-5±0.39×10-5 vs 3.34×10-7±7.45×10-8,P<0.05)level was significantly increased,PD-1 mRNA(2.66×10-6±1.62×10-6 vs 9.62×10-6±6.9×10-6,P<0.05)levels decreased significantly.Flow cytometry results showed that compared with normal pregnant women,the proportion of CD3+ICOS+T cells was significantly up-regulated(0.54±0.39% vs 0.021±0.15%,P<0.05),and CD3+PD-1+ T cell subsets was significantly lower(48.9±4.39% vs 65.1±3.15%,P<0.05).Conclusion:The expression of costimualtory molecules in CD28 family was changed significantly in decidual tissues of patients with URSA,which might correlate with the disorder of local immunological balance in maternal fetal interface and associated with the occurrence of URSA.