Abstract
IgG4 and its role in immune tolerance has been investigated widely. Symptom reduction and improved clinical outcomes in immunotherapy trials are associated with significant increases in allergen-specific IgG4 antibodies. Natural immune tolerance observed in beekeepers and cat owners has also been associated with elevated levels of bee venom and cat allergen-specific IgG4, respectively. Functionally, allergen-specific IgG4 has been shown to reduce the binding of IgE-allergen complexes to B cells, a key step in the initiation of the type 1 hypersensitivity allergic response. In laboratory animal allergy, IgG4 has been described as a “protective/blocking” antibody. However, a consensus on the exact relationship between exposure, IgG4, and tolerance has yet to be reached. In this chapter, we review the factors that require consideration when developing an ELISA for the quantification of allergen-specific IgG4.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Satoguina JS, Adjobimey T, Arndts K, Hoch J, Oldenburg J, Layland LE, Hoerauf A (2008) Tr1 and naturally occurring regulatory T cells induce IgG4 in B cells through GITR/GITR-L interaction, IL-10 and TGF-beta. Eur J Immunol 38:3101–3013. https://doi.org/10.1002/eji.200838193
Jones M, Jeal H, Schofield S et al (2014) Rat-specific IgG and IgG4 antibodies associated with inhibition of IgE-allergen complex binding in laboratory animal workers. Occup Environ Med 71:619–623. https://doi.org/10.1136/oemed-2014-102119
Shamji MH, Kappen J, Abubakar-Waziri H et al (2019) Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol 143(3):1067–1076. https://doi.org/10.1016/j.jaci.2018.09.039
Renand A, Archila LD, McGinty J et al (2015) Chronic cat-allergen exposure induces a TH2 cell-dependent IgG4 response related to low-sensitization. J Allergy Clin Immunol 136:1627–1635. e13. https://doi.org/10.1016/j.jaci.2015.07.031
Hesselmar B, Aberg B, Eriksson B et al (2003) High-dose exposure to cat is associated with clinical tolerance—a modified Th2 immune response? Clin Exp Allergy 33:1681–1685
Platts-Mills T, Vaughan J, Squillace S et al (2001) Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 357:752–756
Rossi RE, Monasterolo G, Coco G et al (2007) Evaluation of serum IgG4 antibodies specific to grass pollen allergen components in the follow up of allergic patients undergoing subcutaneous and sublingual immunotherapy. Vaccine 25:957–964
Subbarayal B, Schiller D, Möbs C et al (2013) Kinetics, cross-reactivity, and specificity of Bet v 1-specific IgG4 antibodies induced by immunotherapy with birch pollen. Allergy 68:1377–1386. https://doi.org/10.1111/all.12236
Nouri-Aria KT, Wachholz PA, Francis JN et al (2004) Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172:3252–3259
James LK, Shamji MH, Walker SM et al (2011) Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies. J Allergy Clin Immunol 127:509–516.e1-5. https://doi.org/10.1016/j.jaci.2010.12.1080
Aalberse RC, Dieges PH, Knul-Bretlova V et al (1983) IgG4 as a blocking antibody. Clin Rev Allergy 1:289
Varga EM, Kausar F, Aberer W et al (2013) Tolerant beekeepers display venom-specific functional IgG4 antibodies in the absence of specific IgE. J Allergy Clin Immunol 131:1419–1421. https://doi.org/10.1016/j.jaci.2012.08.037
Jeal H, Draper A, Harris J et al (2006) Modified Th2 responses at high-dose exposures to allergen: using an occupational model. Am J Respir Crit Care Med 174:21–25
Peng RD, Paigen B, Eggleston PA et al (2011) Both the variability and level of mouse allergen exposure influence the phenotype of the immune response in workers at a mouse facility. J Allergy Clin Immunol 128:390–396.e7. https://doi.org/10.1016/j.jaci.2011.04.050
Portengen L, de Meer G, Doekes G et al (2004) Immunoglobulin G4 antibodies to rat urinary allergens, sensitization and symptomatic allergy in laboratory animal workers. Clin Exp Allergy 34:1243–1250
Krop EJ, Doekes G, Heederik DJ et al (2011) IgG4 antibodies against rodents in laboratory animal workers do not protect against allergic sensitization. Allergy 66:517–522. https://doi.org/10.1111/j.1398-9995.2010.02508.x
Matsui EC, Diette GB, Krop EJ et al (2005) Mouse allergen-specific immunoglobulin G and immunoglobulin G4 and allergic symptoms in immunoglobulin E-sensitized laboratory animal workers. Clin Exp Allergy 35:1347–1353
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Canizales, J. (2019). Measurement of Specific IgG4 Anti-mouse Urine Antibodies. In: Lympany, P., Jones, M. (eds) Allergy. Methods in Molecular Biology, vol 2020. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9591-2_16
Download citation
DOI: https://doi.org/10.1007/978-1-4939-9591-2_16
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-4939-9589-9
Online ISBN: 978-1-4939-9591-2
eBook Packages: Springer Protocols