Improved IgG antibody diagnostics of hypersensitivity pneumonitis and pulmonary mycoses by means of newly evaluated serum antibody ranges and frequencies using IgG ImmunoCAP™

Abstract

Summary

Background

The ranges of most human IgG antibodies against avian, microbial, and chemical antigens between their cut off values and their maximum values detected by IgG ImmunoCAP™ (Thermo Fisher Diagnostics, Freiburg, Germany) are not well known in pulmonary immune-mediated disorders. In addition, for many antigens it is not yet known how frequently their IgG antibodies appear in patients with these lung diseases. Therefore, we evaluated ranges and frequencies of these IgG antibodies.

Methods

The sera of 47,200 patients with suspected hypersensitivity pneumonitis (HP, extrinsic allergic alveolitis) or bronchopulmonary mycoses (mainly allergic bronchopulmonary aspergillosis [ABPA]), which were examined for 32 various IgG antibodies against birds, bacteria, molds, yeasts, and chemicals using the IgG ImmunoCAP™ assay, were evaluated retrospectively.

Results

We found a large spreading of the specific IgG ranges with maximum values from 26 mgA/l for Rhizopus nigricans up to 4640 mgA/l for pigeon. When the maximum values in the literature are also taken into account, the ranges of avian antibodies reach values up to 7280 mgA/l, the ranges of molds and yeasts up to 1707 mgA/l, of bacterial thermoactinomycetes up to 206 mgA/l, and of chemicals up to 139 mgA/l. The evaluated antibody ranges of the individual antigens can be used to decide whether a detected IgG antibody value is weakly, moderately or strongly positive. According to consistent evidence from numerous studies, a strongly positive antibody indicates HP or pulmonary mycosis more likely than a weakly positive antibody. It was found that the antigens of the highest maximum antibody levels—pigeon, budgerigar, parrot, Aspergillus fumigatus—are the causative agents of the most common immune-mediated lung diseases: bird breeder’s lung and pulmonary aspergillosis. Evaluation of the frequencies of eight major IgG antibodies of HP revealed the following rates: pigeon 28%, Aspergillus fumigatus 25%, budgerigar 23%, Penicillium chrysogenum 11%, Saccharopolyspora rectivirgula 7%, Acremonium kiliense 6%, Aureobasidium pullulans 5%, and Thermoactinomyces vulgaris 2%.

Conclusion

This study is the first to evaluate the ranges not only of avian and Aspergillus fumigatus antigens, as has been done up to now, but also of antibodies against 24 other environmental antigens. Quantification of IgG antibodies regarding their specific ranges can help to improve the serodiagnostics of immune-mediated lung diseases. In the lower ranges IgG antibodies are mainly physiological, while higher ranges correlate with the mentioned diseases as HP and ABPA/allergic bronchopulmonary mycoses (ABPM). The determined frequencies of the eight HP antibodies can be helpful in establishing HP screening tests.