Complement activation in anti-phospholipid syndrome: a clue for an inflammatory process?
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.
Cavazzana
Ilaria
I
Reumatologia e Immunologia Clinica, Ospedali Civili and University of Brescia, Brescia, Italy.
Manuela
Nebuloni
N
Irene
Cetin
C
Barbara
Acaia
A
Sara
Saino
S
Orietta
Borghi Maria
BM
Angela
Tincani
T
Francesco
Tedesco
T
Luigi
Meroni Pier
MP
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*
D017152:Antibodies, Antiphospholipid