The association of rheumatoid factor (RF) and lung disease in several immunologically mediated conditions has suggested that it may be physiopathologically relevant. Since previous reports in hypersensitivity pneumonitis (HP) have dealt mainly with the immunoglobulin M (IgM) RF measurement, we studied such antibody activity in other immunoglobulins, to determine the IgG and IgA RF levels in pigeon-HP, and in asymptomatic breeders (AB) and rheumatoid arthritis (RA) as controls. RFs were measured in 35 HP patients, 41 AB, 31 RA controls, and 55 healthy donors by enzyme-linked immunosorbent assay (ELISA) using human or rabbit immunoglobulin G (IgG), anti-IgM, F(ab')2 of IgG, and IgA F(ab')2 conjugates. An affinity chromatography, fragment crystallizable (Fc) preparations of IgG, pepsin digestion, and Western blots were used to confirm RF specificity. We also evaluated anti-avian antibodies (AA) and cross-reacting antibodies. The HP group revealed positive IgM (51.4%), IgG (31.4%), and immunoglobulin A (IgA) (34.2%) RF tests, and these antibody values exceeded the AB reference levels (P<0.02). HP and RA showed a similar frequency and distribution of RFs. Possible immunoassay interferences were excluded. As in other immunologically mediated diseases, IgG and IgA RFs may play a pathogenic role in HP, amplifying the inflammatory reaction, immune-complex formation, and complement activation. IgM-RF producing cells that have been implicated in the presentation of self and foreign antigens, and T-cell activation might induce the isotype switching of RFs.

The assessment of antiavian antibodies is relevant for the study of pigeon breeder's disease; nevertheless, different factors may hamper their accurate detection. The objective of this study was to determine whether an endogenous interfering effect in pigeon breeder's disease might explain the simultaneous presence of IgM, IgG, and IgA antiavian antibodies in high titers as assessed by ELISA. Fifty-nine patients with pigeon breeder's disease, 80 healthy controls, and 47 asymptomatic breeders were studied. To assess possible interfering effects by endogenous immunoglobulins, serum IgG was separated through protein A-Sepharose CL-4B chromatography. Antiavian antibodies were measured in whole and separated samples by ELISA. Since a decline of IgM antiavian antibodies following IgG removal was consistent with a false-positive effect, the causes were studied. High values of IgM, IgG, and IgA antiavian antibodies were found in 47.4% [corrected] of patients with pigeon breeder's disease. An IgM rheumatoid factor activity against IgG was found through ELISA in sera with false-positive IgM antiavian antibodies. Rheumatoid factor binding was confirmed by Western blot. Experimental addition of purified rheumatoid factor to sera with IgG antiavian antibodies replicated the interfering effect. A control group of rheumatoid arthritis with high rheumatoid factor values did not show positive antiavian antibodies tests. No IgG with anti-IgM or anti-IgA activity was found, and the detection of IgA against IgM and IgG was negative. In conclusion, the study of antiavian antibodies might be affected by different immunoassay conditions. An endogenous rheumatoid factor activity produced false-positive IgM results. Other similar interferences warrant a careful evaluation during the serological assessment of pigeon breeder's disease.

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