Serum IgE reactive against small myelin protein-derived peptides is increased in multiple sclerosis patients

Though independent findings suggest roles for the allergic arm of the immune system and myelin-reactive antibodies in MS, myelin-reactive IgE has not been investigated. We have developed a radioimmunoassay that measures reactive IgE, IgG and IgA against short (5-6-mers) myelin protein-derived peptides bearing little to no sequence identity with other human proteins, and which might therefore be targets of a CNS-specific autoimmune attack. Here we show that, irrespective of clinical subtype, MS patients' sera are characterized by a higher frequency of measurable IgE against the peptides. Moreover, in controls with measurable IgE reactive against test peptides, IgG or IgA reactive with the same peptide epitopes is almost always present in vastly greater quantities, whereas in MS subjects peptide-reactive IgA or IgG is often undetectable. The sensitivity of the full assay, when considering overall positive a serum sample that has detectable autoreactive IgE without other competing Igs, is 69% (S.E.: 5%), with a specificity of 87% (S.E.: 9%). We speculate that IgE reactive against CNS target antigens may have both diagnostic and pathogenic significance, particularly if other peptide-specific, potentially blocking Igs are absent.