title: Complement activation in anti-phospholipid syndrome: a clue for an inflammatory process?
abstract: Anti-phospholipid syndrome (APS) is defined by recurrent arterial/venous thrombosis and/or fetal losses in the persistent presence of anti-phospholipid antibodies (aPL). In in vivo experimental models aPL thrombogenic activity is associated with a pro-inflammatory endothelial phenotype (increased adhesion molecule [ADM] expression and leukocyte adhesion) in addition to a pro-coagulant one (tissue factor [TF] expression). This is in line with the in vitro aPL ability to trigger intracellular signalling and to up-regulate ADM, TF and pro-inflammatory cytokine/chemokine expression at the mRNA and protein level in endothelial cells. Comparable effects were also reported in monocytes in vitro. In addition, complement activation is required by aPL to display their thrombogenic activity in in vivo models. Interestingly, complement activation blocking as well as Tumor Necrosis Factor alpha neutralization protect animals from aPL-induced fetal losses. Altogether these findings speak in favour for a role of inflammation in APS in spite of the absence of a clear inflammatory signature in the patients. We could not find any complement (C3c and C4d) deposition in the placentas from 2 late abortions (20 weeks of gestation) in APS women. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are taking place in APS patients.
authors.affiliation: Reumatologia e Immunologia Clinica, Ospedali Civili and University of Brescia, Brescia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavazzana
authors.forename: Nebuloni
authors.initials: N
authors.lastname: Manuela
authors.forename: Cetin
authors.initials: C
authors.lastname: Irene
authors.forename: Acaia
authors.initials: A
authors.lastname: Barbara
authors.forename: Saino
authors.initials: S
authors.lastname: Sara
authors.forename: Borghi Maria
authors.initials: BM
authors.lastname: Orietta
authors.forename: Tincani
authors.initials: T
authors.lastname: Angela
authors.forename: Tedesco
authors.initials: T
authors.lastname: Francesco
authors.forename: Meroni Pier
authors.initials: MP
authors.lastname: Luigi
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D003167:Complement Activation; D005260:Female; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D013927:Thrombosis / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid