Aberrant complement activation in pathological pregnancy
A number of pregnancy complications including recurrent abortion7, premature delivery 8, fetal
intrauterine growth restriction (IUGR) 9, hypertensive
disorders, preeclampsia (PE) 10, HELLP syndrome11 are associated with aberrant complement activation.
And women with inherited or acquired complement system dysfunction is a
risk factor of suffering from these pregnancy disorders. Some complement
activation products are potential serum and urine biomarkers to predict
adverse pregnancy outcomes 12.
Preeclamptic (PE) is a severe and worldwide pregnancy associated disease13, leading to multi-organ dysfunction and sometimes
is life-threatening. C5a and membrane attack complex (MAC, sC5b-9) are
two strong pro-inflammatory products in complement activation cascade,
they significantly elevated in severe PE patients. C5a acts as
chemotactic factors to recruit leukocytes 14 and
induce proteases, free oxygen radicals and pro-inflammatory cytokines15-17. C5a/C5aR interaction can induce trophoblasts to
an anti-angiogenic phenotype. And it inhibits the tube formation and
migration 18. MAC can not only mediate lysis and
apoptosis of trophoblasts but also induce NOD-like receptor family,
pyrin domain containing 3 (NLRP3) activation and then secretion of
pro-inflammatory cytokines 19 . An in vivo
experiment reinforced this conclusion that C6 knock down can
significantly reduce inflammatory processes 20.
(Figure 1) Data shew that urinary sC5b-9 level was finely correlated
with decreased placental growth factor (PlGF) and vascular endothelial
growth factor (VEGF) and increased Soluble fms-like tyrosine kinase-1
(sFlt-1, sVEGFR-1) 21, which forms an anti-angiogenic
status and impairs placenta blood vessel formation. Now, C5-C5a axis is
a promising target for drug development in complement related pregnancy
disorder. It can not only inhibit C5a but also the subsequent generation
of MAC.