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Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis

Data of a German multicentre study

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Abstract

Background

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.

Methods

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.

Results

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.

Discussion

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.

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Abbreviations

CV:

Coefficient of variation

EAA:

Extrinsic allergic alveolitis

FEIA:

Fluorescent enzyme immunoassay

HSA:

Human serum albumin

HP:

Hypersensitivity pneumonitis

MBP:

Maltose-binding protein

mgA/L:

Milligrams of antigen-specific IgG per liter

SD:

Standard deviation

(s)IgG:

Specific immunoglobulin G

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Acknowledgements

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.

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Authors and Affiliations

  1. Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung, Institut der Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Monika Raulf, Ingrid Sander & Frank Hoffmeyer

  2. Malteser Lung- und Allergy Centre Bonn, Bonn, Germany

    Marcus Joest & Joachim Sennekamp

  3. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine University Hospital (LMU), Comprehensive Pneumology Center Munich (CPC-M), Member DZL, German Center for Lung Research, Munich, Germany

    Dennis Nowak & Uta Ochmann

  4. Institute for Occupational and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Alexandra Preisser

  5. University Clinic of Pneumology, Magdeburg, Germany

    Jens Schreiber

  6. Department of Pulmonary Diseases, Fachkrankenhaus Coswig, Centre for Pulmonary Diseases and Thoracic Surgery, Coswig, Germany

    Dirk Koschel

  7. Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Dirk Koschel

Authors
  1. Monika Raulf
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  2. Marcus Joest
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  3. Ingrid Sander
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  4. Frank Hoffmeyer
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  5. Dennis Nowak
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  6. Uta Ochmann
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  7. Alexandra Preisser
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  8. Jens Schreiber
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  9. Joachim Sennekamp
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  10. Dirk Koschel
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Corresponding author

Correspondence to Monika Raulf.

Ethics declarations

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.

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Conflict of Interest

M. Raulf received honorarium for lectures on scientific meetings from HAL Allergy, ThermoFisher Scientific and Astellas. D. Koschel received honorarium for lectures on scientific meetings from Boehringer Ingelheim and Roche. M. Joest received lecture fees for a webinar from ThermoFisher Scientific Phadia. I. Sander, F. Hoffmeyer, D. Nowak, U. Ochmann, A. Preisser, J. Schreiber and J. Sennekamp declare that they have no competing interests.

Cite this as Raulf M, Joest M, Sander I, Hoffmeyer F, Nowak D, Ochmann U, Preisser A, Schreiber J, Sennekamp J, Koschel D. Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis. Data of a German multicentre study. Allergo J Int 2019;28:192–203

https://doi.org/10.1007/s40629-019-0099-x

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Raulf, M., Joest, M., Sander, I. et al. Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis. Allergo J 28, 52–63 (2019). https://doi.org/10.1007/s15007-019-1917-7

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  • DOI: https://doi.org/10.1007/s15007-019-1917-7

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