Induction of autoallergy with an environmental allergen mimicking a self protein in a murine model of experimental allergic asthma

Background: Allergy and autoimmunity are traditionally considered as 2 exclusive entities related to the development of either T(H)2-dominated or T(H)1-dominated immune responses. Objective: This study investigated whether allergic sensitization to a foreign antigen mimicking a self protein can induce allergy accompanied by an autoimmune response. Methods: BALB/c mice were sensitized to human alpha-NAC, an evolutionary conserved component of the nascent polypeptide-associated complex, recently identified as an IgE-reactive autoantigen in patients with severe forms of atopy. By using nitrocellulose-blotted murine lung and skin extracts, purified recombinant human as well as murine alpha-NAC and murine alpha-NAC-derived synthetic peptides, the IgE, IgG1, and IgG2a antibody responses were measured, and their epitope specificity was mapped. Results: Cross-reactivity of IgE and IgG antibodies with murine alpha-NAC was found in mice sensitized with human alpha-NAC. The biological relevance of the antibody response was demonstrated by the induction of immediate skin reactions in sensitized mice and by the fact that skin sensitivity could be passively transferred with serum to naive mice. Antigen challenge of sensitized mice resulted in airway inflammation accompanied by eosinophil and neutrophil accumulation, airway hyperresponsiveness to methacholine and perivasculitis of lung veins. Conclusion: Our data demonstrate that sensitization with a foreign antigen mimicking self can induce an allergic immune response of a mixed T(H)2 and T(H)1 profile that is associated with autoreactivity. Cross-sensitization to self may represent an important pathomechanism involved in the maintenance of severe and chronic forms of allergy.