Increased complement C4d deposition at the maternal-fetal interface in unexplained recurrent miscarriage

C4d is a footprint of antibody-mediated classical complement activation, and has evolved as a useful diagnostic marker of antibody-mediated rejection. It is unknown if complement activation, as reflected by C4d deposition plays a role in unexplained recurrent miscarriage. In a case-control study products of conception of 35 women with three or more unexplained consecutive miscarriages within 20 weeks of gestation with the same partner (case group), 22 women with one spontaneous sporadic miscarriage and no history of complicated pregnancy(ies) (control group 1), and 40 women who underwent an elective abortion for psychosocial reasons (control group 2) were included. Immunohistochemical staining for C4d was performed on products of conception. Positivity for C4d was scored semi-quantitatively. C4d deposition was present in products of conception of 14 out of 35 women with unexplained recurrent miscarriage (40.0%), compared to 6 out of 22 women with a sporadic miscarriage (27.3%), and 4 out of 40 women with an elective abortion (10.0%) (p=0.020). C4d is increased at the maternal-fetal interface in women with unexplained recurrent miscarriage, which may reflect an aberrant anti-fetal immunity in these women. Further knowledge of the specific pathogenic mechanism may lead to the development of new treatment strategies for this group of women

Differential immunoregulation in successful oocyte donation pregnancies compared with naturally conceived pregnancies

In oocyte donation (OD) pregnancies, there is a higher level of antigenic dissimilarity between mother and fetus compared with naturally conceived (NC) pregnancies. We hypothesize that a higher degree and/or a different type of immunoregulation is necessary to maintain an uncomplicated OD pregnancy. Different immunological aspects of successful OD pregnancies (n=28) were compared with those of NC pregnancies (n=51), and non-donor IVF (n=20) pregnancies. Maternal peripheral blood mononuclear cells (mPBMCs) were characterized by flow cytometry; the outcome correlated with the number of mother child HLA mismatches. The fetus-specific alloreactivity of mPBMCs was measured in a mixed lymphocyte reaction. The percentages of CD4(+)CD25(bright) and CD4(+)CD25(dim) cells were higher in mPBMCs of OD and IVF pregnancies compared with NC pregnancies. The percentage of CD4(+)CD25(dim) cells in mPBMCs of OD pregnancies correlated positively with the number of HLA mismatches. Functional studies showed a lower proliferative response to umbilical cord blood by mPBMCs in OD pregnancies. In conclusion, we found a higher degree of peripheral immunoregulation in OD and IVF pregnancies compared with NC pregnancies. A higher number of HLA mismatches in successful OD pregnancies leads to increased percentages of activated T cells in peripheral blood, but not to a higher alloreactivity to the fetus. These studies show that immunoregulation in OD pregnancy is different from that in NC pregnancies. The antigenic dissimilarity in OD pregnancies may play a role in the pathophysiology of preeclampsia. (C) 2013 Elsevier Ireland Ltd. All rights reserved