PURPOSE:In hypersensitivity pneumonitis (HP) the nature and physicochemical properties of the causative antigens have not been entirely defined. Since antiavian antibodies (AA) together with positive rheumatoid factor (RF) tests are frequently found in pigeon HP, and we have suggested a possible autoimmune pathogenesis of the disease, the characteristics of potential foreign and self targets antigens which may explain this hypothesis were studied.
METHODS:The serological spectrum in 35 HP patients and 41 asymptomatic breeders (AB) was evaluated through ELISA and Western blot. Pigeon serum, avian IgG also known as IgY, and mammalian gammaglobulins including human IgG were prepared by chromatography. The molecular weight (MW), glycosylation patterns and immunogenic characteristics of these antigens were determined through electrophoresis, affinity chromatography, or using biotinylated lectins, and their ability to induce specific antibodies. Additionally, the binding activity of AA and RF was assessed by competitive assays.
RESULTS:A high frequency of HP patients (51.4%) showed positive AA and RF tests in comparison to AB (4.8%) (P<0.02). Antiavian activity involved particularly pigeon serum antigens with a MW of ∼65 KDa, and RF was demonstrated using aggregated rabbit or human IgG. Heavy chains of pigeon gammaglobulins were identified as the main targets of AA studying chronic HP patients. Avian IgG preparations revealed a predominant Griffonia simplicifolia-I lectin reactivity, and induced polyclonal antibodies to specific oligosaccharides including Galα1–4Gal epitopes. Additionally, a more common inhibition of AA levels than RF values was found using pigeon IgG in competitive studies.
CONCLUSION:Antigenic evaluation of pigeon serum revealed that a group of distinctive glycoproteins were the main HP targets. This specific N-glycosylation pattern was identified also in heavy chains of pigeon IgG, and associated with a high frequency of AA in HP patients with positive RF tests. It is possible that a break of tolerance to self IgG involves at least in part specific oligosaccharides and/or non-glycosylated antigens on foreign gammaglobulins.
CLINICAL IMPLICATIONS:This study deals with the characterization of pigeon antigen and a possible autoimmune pathogenesis in hypersensitivity pneumonitis.
DISCLOSURE:Diana Aguilar-Léon, No Financial Disclosure Information; No Product/Research Disclosure Information