Therapeutic potential of peptides in allergic disease

Immunotherapy with crude allergens prevents allergic symptoms in many patients, but its effects are temporary and variable. This type of intervention provokes a transient increase in IgE antibody synthesis that may produce untoward side effects. Recent research has suggested that such immunotherapy downregulates T-cell activity, indicating that regulation of proinflammatory T cells may be a critical mechanism of the therapeutic response. Animal studies have shown that T cells can be rendered anergic by the administration of nonimmunogenic, T-cell-active peptides. Peptides prepared by urea denaturation of purified allergens and by pepsin digestion of crude allergens have been evaluated in humans. Although evidence of specific immunosuppression was noted, allergic reactions occurred as well. Subsequently, researchers synthesized peptides representing short sequences from the protein chains of principal allergens, such as Amb a I of ragweed and Fel d I of cat. Assays of proliferation of T-cell lines from ragweed- and cat-sensitive patients have shown that relatively short sequences from these proteins are responsible for a major portion of the activity of the whole protein. One such cat peptide has shown no reactivity with human IgE. The characteristics of these peptides suggest they should be evaluated further in clinical trials of allergic patients. The anticipated outcome would be prolonged T-cell downregulation, which might result in suppression of late-phase allergic inflammation and IgE antibody synthesis. The question whether such changes will reduce clinical reactivity sufficiently to be clinically useful remains to be answered in future studies.