Evaluation of levels, specificity and pathophysiology of anti-C1q autoantibodies in pregnancy

C1q, the recognition molecule of the classical pathway of the complement (C) system, has been shown to represent a double-edged molecule in determining pregnancy outcomes. Being essential for the correct placentation process, C1q is synthesized by extravillous trophoblasts to promote interstitial migration and to act as a molecular bridge between endovascular trophoblast and maternal endothelial cells of the spiral arteries. In animal models, C1q deficiency caused the development of a dysfunctional placenta and pre-eclamptic (PE)-like symptoms. This C component can be the target of an antibody response. Autoantibodies targeting C1q were first recognized in the serum of Systemic Lupus Erythematosus (SLE) patients, and are associated to the onset of lupus nephritis. Nonetheless, the incidence of anti-C1q is estimated to be between 2-8% in the general healthy population. We recently evaluated the levels of anti-C1q in PE gestations, in healthy spontaneous and in heterologous assisted reproductive technology (ART) pregnancies (which present a higher risk of developing PE). Unexpectedly, our results indicate that PE and ART pregnant women were characterized by lower levels of anti-C1q compared to healthy mothers. We characterized the specificity of these autoantibodies -anti-collagen-like region (CLR) or anti-globular domain (ghC1q)- and their possible physiological role in pregnancy. We observed a higher adhesion percentage and lower trans-endothelial migration of HTR8/SVneo in the presence of anti-CLR compared to anti-ghC1q antibodies. Our results indicated that anti-CLR antibodies could induce a stable adhesion of trophoblast cells on DECs, which probably inhibited the trans-endothelial migration process.