Unexplained fetal death is associated with changes in the adaptive limb of the maternal immune response consistent with prior antigenic exposure

Abstract

Objective: The causes of fetal death are largely unknown. CD4 T cells have been classified according to the expression of the CD45 isoforms into 'naive-like' T cells (CD45RA) and 'memory-like' Tcells (CD45RO). An increase in the percentage of the CD45RO has been interpreted as indicating prior antigenic exposure of the host and, in newborns, evidence of infection. The purpose of this study wasto determine whether unexplained fetal death was associated with a change in the proportion of 'naive-like' and 'memory-like T cells' in the maternal blood, as determined by the CD45 isoforms on the surfaceof CD4+ lymphocytes.Study design: A prospective study was conducted to compare the CD45 sub-population of lymphocytes in patients with intrauterine fetal death (n = 26) and normal pregnancy(n = 89). The percentages of CD45RA+, CD45RO+ and CD45RA+/CD45RO+ on CD4+ T lymphocytes were determined in maternal blood using flow cytometry and monoclonal antibodies. Results were reported asa percentage of CD4+ lymphocytes. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant.Results: Patients with intrauterine fetal death had a higherpercentage of CD45RO+ CD4+ T lymphocytes than normal pregnant women (fetal death: median 57.7%, range 35.4-78.6 vs. normal pregnancy: median 49.9%, range 19.1-86.8; p = 0.004). Fetal death was associatedwith a lower median percentage of CD45RA+ CD4+ lymphocytes than in normal pregnant women (fetal death: median 32.3%, range 15.3-58.0 vs. normal pregnancy: median 40.2%, range 11.2-67.3; p = 0.01). Therewas no significant difference in the percentage of cells with dual expression (CD45RA+/CD45RO+) between the study groups.Conclusion: Prior exposure to microbial products (bacterial or viral)or other unidentified antigens may result in a shift of the sub-population of 'naive-like' T cells to 'memory-like' T cells in mothers with unexplained fetal death.