Toll-like receptors: another player in the pathogenesis of the anti-phospholipid syndrome.
The anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self phospholipid (PL)--binding proteins. Although APS is considered as an autoantibody-mediated disease, there is now evidence that anti-phospholipid antibodies (aPL) are necessary but not sufficient to trigger some of the clinical manifestations of the syndrome. For example, mediators of the innate immunity are recognized to be additional second hits able to induce the thrombotic events in the presence of aPL. Finally, environmental agents - in particular infectious ones - were reported to act as triggers for the production of autoantibodies cross-reacting with PL-binding proteins as well as inflammatory stimuli that potentiate the aPL thrombogenic effect. Altogether, these findings suggest a role for the innate immunity in APS pathogenesis. Toll-like receptors (TLR) are receptors that induce prompt inflammatory responses and mediate functional activation in immune effector cells. There is evidence that aPL, and in particular anti-beta(2) glycoprotein I (beta(2)GPI) antibodies, may activate endothelial cells and monocytes through TLR-4-dependent signalling. Whether or not TLR may behave as surface receptors for beta(2)GPI is still matter of research. Drugs or molecules able to interfere with TLR involvement may represent new therapeutic approaches for APS.
Raschi
E
E
Allergy, Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Department of Internal Medicine, University of Milan, Milan, Italy.
Borghi
M O
MO
Grossi
C
C
Broggini
V
V
Pierangeli
S
S
Meroni
P L
PL
D000937:Antigen-Antibody Reactions; D016736:Antiphospholipid Syndrome / Q000209:etiology* / Q000235:genetics; D015551:Autoimmunity / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
D051193:Toll-Like Receptors