New facet of antiphospholipid antibodies.
Since the aCL test was first described, several reports have described the heterogeneity of aPL, which binds to different anionic phospholipids, proteins, or to a phospholipid-protein complex. It has been recently reported that antiphospholipids (aPLs) from the sera of patients with the antiphospholipid syndrome (APS) are able to bind some newly identified antigens, the lyso(bis)phosphatidic acid (LBPA), lipid restricted to the late endosomes, and the sulfatides, acidic glycosphingolipids involved in the hemostatic process. Of interest, aLBPAs are present in the sera of a large number of patients with APS showing similar sensitivity and specificity compared to anti-beta(2) glycoprotein I antibodies (abeta(2)-GPIs) and close association with lupus anticoagulant. Moreover, beta(2)-GPI binds to sulfatides and the majority of the aPL reacting with cardiolipin-beta(2)-GPI complex also react with the sulfatide-beta(2)-GPI complex. Different mechanisms involved in the production of autoantibodies in autoimmune diseases have been proposed and, among them, apoptosis or programmed cell death seems to play a leading role. The relocation of CL and its metabolites during apoptosis may represent an in vivo trigger for the generation of aCL, and the higher reactivity of sera from APS patients to monolysocardiolipin, the immediate degradation product of mitochondrial CL validates this hypothesis. Finally, increasing evidence suggests that oxidative stress could be a pathogenic link between aPL and thrombosis, and antioxidant treatment may have some efficacy in preventing the clinical manifestations of this syndrome.
Valesini
Guido
G
Dipartimento di Clinica e Terapia Medica Applicata, Cattedra di Reumatologia, Università La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy. guido.valesini@uniroma1.it
Alessandri
Cristiano
C
D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000209:etiology*; D017209:Apoptosis; D002308:Cardiolipins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000150:complications; D015227:Lipid Peroxidation; D008246:Lysophospholipids / Q000378:metabolism; D018384:Oxidative Stress; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D006023:Glycoproteins; D008246:Lysophospholipids; D053482:beta 2-Glycoprotein I; C032881:lysophosphatidic acid