Phospholipid antibody

As a high incidence of arteriovenous thrombosis is described in patients with systemic lupus erythematosus (SLE), Matsuda et al. (Ml8) tried to demonstrate a relationship between the presence of anti-phospholipid antibodies and Lp(a) concentrations. They found that serum Lp(a) concentrations were increased in patients with SLE independent of the presence of anti-phospholipid antibodies. Borba et al. (B18) confirmed these findings and also could not correlate Lp(a) concentrations with anti-cardiolipid antibodies. 

Antibodies directed against (32 -GPI further enrich the protein on the cell surface but these promote a p38 Map-kinase signalling cascade which results in increased expression of tissue factor (TF) and reduced expression of thrombomodulin on the surface of cells. TF is a major initiator of coagulation and increased levels of TF expression have been measured on endothelial cells treated with anti-phospholipid antibodies and on monocytes both ex vivo and in vivo (Yasuda et al., 2005 Lopez-lira et al., 2005, Lopez-Pedrera et al., 2006). Thrombomodulin is a potent anti-coagulant protein which limits activation of thrombin, so the net result of circulating anti-phospholipid antibodies is to usurp the anti-coagulative, protective mechanism and initiate a pro-coagulation cascade. 

The neurologic involvement in Crohn s disease can be attributed to several mechanisms including autoimmunity. For the predominant arterial cerebrovascular involvement, the state of hyper coagulation secondary to thrombocytosis and increase in factor V, Vm and fibrinogen are probable mechanisms. However, since anti-phospholipid antibodies and lupus anticoagulant are confirmed in many cases, autoimmune mechanisms are also involved (Santos et al., 2001). 

Facer, C. A., and Agiostratidou, G. (1994). High levels of anti-phospholipid antibodies in uncomplicated and severe Plasmodium falciparum and in P. vivax malaria. Clin. Exp. Immunol. 95,304—309. 

However, false positive tests for platelet factor 4/heparin antibodies can occur in patients with the phospholipid antibody sjmdrome or systemic lupus er)4 hematosus, as illustrated by the results of a study in 42 such patients, of whom 32 were positive for platelet factor 4/heparin IgG antibodies and 24 were positive for platelet factor 4 antibodies [75. However, there were no abnormalities in heparin-induced platelet activation or aggregation. 

Matsumoto, Y. Kono, R. Anraku, H. Lipophilic dye for immobilized lipid antigen for immunoassay of anti-phospholipid antibody. Jpn. Kokai Tokkyo Koho JP 08105891, 1996 Chem. Abstr. 1996,125, Sim. 

Phospholipid vesicles, uncoated or polyethylenglycol-coated. They can be used to vehicle dtugs, antibodies or nucleic acids to target cells. 

Alving, C. R. (1984). Natural antibodies against phospholipids and liposomes in humans, Biochem. Soc. Trans.. 12. 342-344. 

Antiphospholipid antibodies include lupus anticoagulants (LAs) and anticardi-olipin (aCL) antibodies. Lupus anticoagulants are immunoglobulins that are characterized by their ability to inhibit phospholipid-dependent coagulation assays. In contrast, aCL antibodies are measured in an enzyme-linked immunosorbent assay... 

Some 5-25 per cent of individuals suffering from haemophilia A develop anti-factor VIII antibodies, and 3-6 per cent of haemophilia B sufferers develop anti-factor IX antibodies. This complicates treatment of these conditions and, as mentioned previously, one approach to their treatment is direct administration of factor Vila. The therapeutic rationale is that factor Vila could directly activate the final common steps of the coagulation cascade, independently of either factor VIII or IX (Figure 12.1). Factor Vila forms a complex with tissue factor that, in the presence of phospholipids and Ca2+, activates factor X. 

Baeza, I., Levya, E., Campos, B., Lara, M., Ibanez, M., Farfan, N., Orozco, J., Flores-Romo, L., Hernandez-Pando, R., and Wong, C., Antibodies to non-bilayer phospholipids arrangements induce a murine autoimmune disease resembling human lupus, Eur. J. Immunol., 34, 576, 2004. 

Through van der Waals and hydrophobic interactions, CNTs were functionalised and made water soluble by the strong adsorption of phospholipids (PLs) grafted onto amino-terminated polyethylene glycol (PEG). The group of Dai bound nucleic acids (DNA and RNA) and proteins to CNTs for specific detection of antibodies (Chen et al., 2003 Kam et al., 2005a, b Liu et al., 2007b). 

M. L. Pisarchick and N. L. Thompson, Binding of a monoclonal antibody and its Fab fragment to supported phospholipid monolayers measured by total internal reflection fluorescence microscopy,. Biophys. J. 58, 1235-1239 (1990). 

Cardiolipin or diphosphatidyl glycerol is one of the most ancient membrane phospholipids from phylogenic aspects. It is surprising for such a complex molecule as cardiolipin to have evolved as one of the major membrane lipids in prokaryotics, when steroids such as cholesterol and phytosterols did not. In eukaryotic cells, cardiolipin is exclusively localized within the mitochondria where it is particularly emiched in the outer leaflet of the inner membrane. Even though a molecular structure of cardiolipin has been conserved in entire organisms, its biological significance has escaped attention except in the case of anti-cardiolipin auto-antibodies which are clinically associated with the Wasserman reaction. 

It can be seen from Figure 1 that the choline-containing phospholipids, phosphatidylcholine and sphingomyelin are localized predominantly in the outer monolayer of the plasma membrane. The aminophospholipids, conprising phosphatidylethanolamine and phosphatidylserine, by contrast, are enriched in the cytoplasmic leaflet of the membrane (Bretcher, 1972b Rothman and Lenard, 1977 Op den Kamp, 1979). The transmembrane distribution of the minor membrane lipid components has been determined by reaction with lipid-specific antibodies (Gascard et al, 1991) and lipid hydrolases (Biitikofer et al, 1990). Such studies have shown that phosphatidic acid, phosphatidylinositol and phosphatidylinositol-4,5-fc -phosphate all resemble phosphatidylethanolamine in that about 80% of the phospholipids are localized in the cytoplasmic leaflet of the membrane. 

Figure 2.10. Schematic diagram of coupling of a thiolated antibody to a linker lipid (maleimide-PEG-phospholipid) which is part of a preformed liposome. The resulting thioether bond is meta-bolically stable. The strategy shown here was used to synthesize OX26-immunoliposomes [111].

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