Increased C4d and Bb immunoreactivity and decreased MBL immunoreactivity characterise first-time pathologic first-trimester miscarriage: a case-control study.

The role of the complement system in first-time pathologic first-trimester miscarriage was investigated. In this case-control study, tissue samples of 126 women with pathologic miscarriage and termination of normal pregnancies were assessed. The pathologic pregnancy group consisted of 40 women with missed miscarriage, 13 women with incomplete miscarriage and 10 women with a blighted ovum. The control group consisted of 63 normal-appearing pregnancies. Immunoreactivity for C4d, Bb and MBL was evaluated in the deciduas and villous trophoblasts separately using a semi-quantitative histological scoring system (H-score). C4d and Bb H-scores were higher and MBL H-score was reduced in the deciduas and villous tissues from pathologic miscarriage compared to termination of pregnancies (p = .003 and p = .001; p = .011 and p < .001; p < .001 and p < .001, respectively). C4d and Bb activities were increased and MBL activity was decreased in human first-time pathologic first-trimester miscarriage. We suggest that three complement pathways may play a role in human first-time pathologic first-trimester miscarriage. Impact statement Previous studies focussed on complement proteins related to a single complement pathway in cases often associated with antiphospholipid syndrome (APS) or recurrent miscarriage. In APS-related cases, the classical pathway is activated. In antibody-dependent and in antibody-independent mouse models of foetal loss, classical and alternative pathways are activated, respectively. Lectin pathway deficiency has been reported in some recurrent miscarriage. The complement pathway or pathways, which have a role in human pathologic miscarriage was the starting point of this study. There has been no study done till now reporting the role of the three complement pathways in human pathologic miscarriage. In this study, we found increased classical and alternative complement pathway activities and decreased lectin pathway activity in tissues from first-time pathologic human miscarriage.