Squalene Antibodies with Lipid Antigens
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Squalene Antibodies with Lipid Antigens |
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Asa et al. (2000) purported that Gulf War Syndrome patients vaccinated prior to deployment exhibited antibodies to SQE which were not observed in normal humans. However, this Western blot-type assay has been severely criticized for lack of proper positive or negative controls to validate the purported ability to detect specific anti-SQE antibodies (Alving and Grabenstein, 2000). Immunological assays of this type must incorporate negative specificity control for nonspecific binding of IgG. This could have been easily accomplished by substituting a similar oil molecule such as SQA, a hydrogenated form of SQE. Yet, the authors overlooked this fundamental control (Alving and Grabenstein, 2000). Therefore, the specificity of their assay for detecting antibodies to SQE remains unproven. In fact, a recent National Academy of Sciences report states, "The committee does not regard [the Asa et al.] study as providing evidence that the investigators have successfully measured antibodies to squalene" (Committee on Gulf War and Health, in press). Monoclonal antibodies to SQE were shown here to cross-react with several other lipid antigens including DMPC, DMPG, Lipid A, hexadecane, stearylamine, cholesterol, arachidic acid, behenic acid, palmitic acid, stearic acid, lignoceric acid, myristic acid, and pristane. The data suggests that DMPC and DMPG bind to a subsite in the antibody. While the antibody reacted strongly with DMPC, it did not react nearly as strongly with DMPG (Table III). DPMC and DMPG both have the same fatty acids. If they were binding at the SQE subsite of the antibody, the antibodies would be expected to bind to them equally. Since the antibodies bound to DMPC more so than DMPG, and the only structural difference between them is the head group, they are most likely binding at a different subsite than SQE. All of the mAbs cross-reacted with at least one lipid antigen other than SQE. This suggests that antibodies to other lipids may also cross-react with SQE. Since Asa et al. (2000) did not assay for antibodies to other lipids, their purported anti-SQE activity may be antibodies to other lipids which have been previously shown to occur in humans with autoimmune diseases (Meager et al., 1999). With the specificity of these antibodies now described, studies elucidating relationship between antibodies to SQE and normal body functions or illness can be investigated. Comparison of anti-squalene antibody levels of deployed vs. non-deployed Gulf War veterans and veterans with vs. without Gulf War Syndrome symptoms is the next line of investigation (Office of the Army Surgeon General, 2000). |
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