Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis
Specific (s)IgG antibodies against environmental and occupational antigens, especially from bacteria, moulds, yeasts, birds and chemicals play an important role for hypersensitivity pneumonitis (HP). An increased serum level of sIgG is one criterion in the diagnostic procedure of HP and crucial for the detection of the triggering antigen for successful avoidance of further exposure. In contrast to specific IgE, sIgG concentrations in healthy individuals vary greatly depending on the antigen, which makes it difficult to differentiate from patients with HP. The aim of this study is to update or establish sIgG-reference values for important HP antigens in a healthy blood donor group.
Therefore a study including six clinical centres in Germany was conducted to collect sera from 121 subjects without any signs of HP and without obvious exposure to potential HP antigens. Specific IgG to 32 typical HP antigens were quantified by ImmunoCAP (ThermoFisher Scientific; Phadia, Uppsala, Sweden). For validation selected measurements were repeated, total IgG was determined, sera were tested for unspecific binding with the human serum albumin ImmunoCAP Ro401, and influence of potential confounders was analysed. Statistical distribution of the antigen-specific IgG values was evaluated and the nonparametric method of percentile calculation was applied.
The levels of IgG antibodies to the different antigens varied considerably in the study group from < 0.02 to 726 mgA/L. Low sIgG levels were found against the chemicals and the highest levels to fungal antigens, especially to Aspergillus fumigatus and Botrytis cinerea. For three isocyanates, three acid anhydrides, Trichosporon pullulans and Acremonium kiliense reference values were proposed for the first time. For several avian antigens, moulds, and bacteria pre-existing reference values nearly could be confirmed without significant deviations, but already the 90 % quantile for sIgG against Penicillium chrysogenum, Aspergillus fumigatus and pigeon antigen (Ge91) clearly exceeded the pre-existing values. In contrast, the 97.5 % quantile value for Candida albicans was nearly half of the pre-existing cut-off value.
In most cases specific IgG values were not significantly influenced by smoking and gender and most of them were unaffected by age. For implementation of these sIgG reference values into the routine diagnosis of HP, we provide an online available calculator to rank measured sIgG concentrations to the 32 different ImmunoCAP antigens.
Keywordsantigen specific IgG diagnosis hypersensitivity pneumonitis reference values extrinsic allergic alveolitis
Coefficient of variation
Extrinsic allergic alveolitis
Fluorescent enzyme immunoassay
Human serum albumin
Milligrams of antigen-specific IgG per liter
Specific immunoglobulin G
The authors are thankful for the support of ThermoFisher Scientific, who had provided ImmunoCAPs/reagents free of charge. Neither the design of the study nor the evaluation of the data were influenced by ThermoFisher Scientific. We thank C. Bittner, Hamburg, for help in collecting the samples, B. Kendzia, Bochum, for statistical support and U. Meurer, Bochum, for skilful technical assistance.
The study design and the protocol were reviewed and approved by the ethical committee of the Technische Universität Dresden (EK 195052014) in accordance with the Declaration of Helsinki and ethical approval was obtained from the local ethic committee of each centre.
- 1.Riario Sforza GG, Marinou A. Hypersensitivity pneumonitis: a complex lung disease. Clin Mol Allergy. 2017;15:6. https://doi.org/10.1186/s12948-017-0062-7Google Scholar
- 2.Nogueira R,Melo N,Novais E, Bastos H,Martins N, Delgado L, et al. Hypersensitivity pneumonitis: antigen diversity anddiseaseimplications. Pulmonol. 2018;https://doi.org/ 10.1016/j.pulmoe.2018.07.003Google Scholar
- 5.Sennekamp J, Müller-Wening D, Amthor M, Baur X, Bergmann K-C, Costabel U, et al. Empfehlungen zur Diagnostik der exogen-allergischen Alveolitis. Arbeitgemeinschaft Exogen-Allergische Alveolitis der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP) und der Deutschen Gesellschaft für Allergologie und Klinische Immunologie (DGAKI). Pneumologie. 2007;61:52–6. Guidelines for diagnosing extrinsic allergic alveolitis (hypersensitivity pneumonitis) (German Extrinsic Allergic Alveolitis Study Group)CrossRefGoogle Scholar
- 7.Kränke B, Woltsche M, Woltsche-Kahr I, Aberer W. IgG-Antikörper gegen „EAA-spezifische Umweltantigene“ Die Problematik der Normalwertdefinition. Allergologie 2001;24:145–54Google Scholar
- 11.Sennekamp J, Lehmann E, Joest M. Berufsbedingte exogen allergische Alveolitis. Arbeitsmed Sozialmed Umweltmed 2015;50:38–52Google Scholar
- 14.Rodrigo MJ, Benavent MI, Cruz MJ, Rosell M,Murio C, Pascual C, Morell F. Detection of specific antibodies to pigeon serum and bloom antigens by enzyme linked immunosorbent assayinpigeonbreeder’sdisease. OccupEnvironMed. 2000;57:159–64Google Scholar
- 15.Sennekamp H-J. Extrinsic allergic alveolitis, Hypersensitivity pneumonitis. Munich, Orlando: Dustri-Verl. Feistle; 2004. ISBN 3-87185-309-7Google Scholar
- 18.Pronk A, Preller L, Raulf-Heimsoth M, Jonkers ICL, Lammers J-W, Wouters IM, et al. Respiratory symptoms, sensitization, and exposure response relationships in spray painters exposed to isocyanates. Am J RespirCritCareMed. 2007;176:1090–7Google Scholar
- 19.Hemmer W, Altmann F, Holzweber F, Gruber C, Wantke F, Wöhrl S. ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD) epitopes and can cause false-positive test results in patients with high anti-CCD IgE antibody levels. J Allergy Clin Immunol. 2018;141:372–81CrossRefGoogle Scholar