Anti-C1q autoantibodies in pregnancy: a potential biomarker for preeclampsia onset in ART gestation?

Objective. C1q protein, the classical complement pathway ac­tivator, is a crucial player in early placentation, promoting tro­phoblast invasion and spiral artery remodelling. C1q-deficient mice display preeclamptic symptoms. Despite being prevalent in autoimmune diseases (AIDs), anti-C1q autoantibodies (an­ti-C1q) are present in 2-8% of the healthy population. In our previous study, elevated anti-C1q levels were observed in the first trimester of healthy pregnancies, contrasting with lower levels in women developing preeclampsia (PE) and in oocyte donation pregnancies (OD), which have a high risk of PE. This study aims to characterize the specificity of anti-C1q in phys­iological pregnancy compared to those found in pathological conditions.
Materials and Methods. Sera from healthy spontaneous, PE, and OD pregnancies, followed at the IRCCS Burlo Garofo­lo (Trieste, Italy), were collected at each trimester. Pregnant women affected by autoimmune diseases were also included.
Results. In healthy pregnancies anti-C1q targets primarily the globular domain (g) of C1q, in contrast to AID-associated an­ti-C1q that recognize its collagen-like region (CLR) (P-value = 0.0291). Immunoglobulin subclass analysis revealed IgG2 prevalence in both healthy and AID pregnancies, suggesting a shared immunological response. Functional assays demon­strated that healthy pregnancy-associated anti-C1q modulat­ed the classical complement pathway activation, potentially in a protective manner (% functionality with gh = 87.5 ± 6.1, with CLR = 101.7 ± 5.5, with no anti-C1q = 100.0 ± 6.2).
Conclusions. This research highlights anti-C1q functional specificity in healthy pregnancies, emphasizing a unique tar­geting of C1q globular domain. Observed pathogenic roles of anti-CLR autoantibodies underscore potential immunological role to pregnancy complications. Further investigations are needed to unveil mechanisms and assess their possible use as early predictive biomarkers of PE.