Complement activation and pregnancy failure.
Pregnancy represents a physiologic condition where maternal immune system tolerates the semi-allogenic fetus. The fetal tissues are directly exposed to the maternal blood with potential attacks from maternal immune system, including the activation of complement cascade. Small amounts, of both early and late components, of complement are physiologically found in the placenta, maybe in relation to the vascular remodeling process. A significant increase of complement activation was associated with different pathologic pregnancy outcomes, namely pre-eclampsia, recurrent spontaneous abortions, intra-uterine growth retardation, and anti-phospholipid syndrome (APS). In some, but not in all, mice models of APS, complement activation plays a major role in pregnancy loss, with a massive accumulation of C3 in the placenta, while C3 deficient mice didn't show fetal resorption. Basing on these findings, anti-phospholipid antibodies and complement activation (via C3a, C5a, and MAC) may cooperate in triggering a local inflammatory process, eventually leading to placental thrombosis, hypoxia, and neutrophil infiltration. However, histological analysis of human placenta tissues from APS women shows small rather than widespread inflammation. In a similar manner, complement activation can be detected in human APS placentas but without any relationship with pregnancy outcome and therapy. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are really taking place in APS.
Tincani
Angela
A
UO Reumatologia, Spedali Civili di Brescia, Piazzale Spedali Civili 1, 25100 Brescia, Italy.
Cavazzana
Ilaria
I
Ziglioli
Tamara
T
Lojacono
Andrea
A
De Angelis
Valentina
V
Meroni
Pierluigi
P
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000150:complications*; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000276:immunology; D006801:Humans; D051379:Mice; D010920:Placenta / Q000098:blood supply / Q000276:immunology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*
D017152:Antibodies, Antiphospholipid; D003165:Complement System Proteins