Experimental induction of autoantibodies to IgG by pigeon IgY

Abstract

Abstract Background IgG is a frequent target of autoantibodies in a variety of experimental and clinical settings. Interestingly, the possible antigens (Ag) that may induce such a break of tolerance have not been fully studied. Since our previous observations showed the frequent co-occurrence of antibodies (Abs) to pigeon IgY and self-reactivity to IgG in hypersensitivity pneumonitis secondary to avian exposure, we decided to evaluate experimentally the role of IgY in this kind of autoimmune reactivity. Objective To study whether pigeon IgY induces anti-IgG reactivity in an experimental model in which foreign and self-immunoglobulins are phylogenetically related. Methods IgY was purified from pigeon (Columba livia) eggs, prepared in Freund’s adjuvant and immunized to Balb/c mice. Abs production to foreign (IgY) and self-antigen (mouse IgG) were evaluated by ELISA and Western blot. Tregs (CD4+CD25+Foxp3+) were also studied by flow cytometry since the first evidences suggested a T-cell dependent Ab reactivity. Results IgG with anti-IgY activity occurred 2 weeks after immunization. Autoantibodies were predominantly IgG and bind Fc fractions of IgG. Immunoglobulins to self-IgG showed a gradual increase and they persisted for 3 weeks. A correlation between high levels of autoantibodies and elevated Tregs was also found. Conclusions Pigeon IgY induced autoantibody production, it was predominantly IgG, follows a kinetic similar to soluble immune complexes formation, and bind the Fc fraction of IgG. T-cell analyses suggested a Tregs dependent reactivity. The break of tolerance to self-IgG in mammals has not been previously studied using a phylogenetically related Ag.