IgG4

Last edited 06/2020

IgG4 is usually formed following repeated immunization; it may be involved in allergy.

IgG4 may be absent in IgA deficiency.

In serum of healthy individuals, IgG4 antibodies comprise the smallest fraction (< 5%) of IgG antibodies (1)

IgG4 has been extensively studied in models of chronic allergen exposure (1)

• IgG4 antibodies possess exclusive structural and functional characteristics suggesting anti-inflammatory and tolerance-inducing effects
• in beekeepers naturally exposed to bee venon high levels of bee venom-specific IgG4 are found to play a protective role against severe hypersensitivity reactions triggered by the bee venom allergen phospholipase (PLA2)
• is in contrast to the situation in bee-venom allergic individuals that exhibit high titers of PLA2-specific IgE and are at risk of IgE-mediated anaphylaxis when stung
• increased IgG4-specific antibodies correlate with allergen tolerance and can be measured in tolerant animal laboratory workers chronically exposed to rodent allergens
• also seen in individuals undergoing AIT (allergy immunotherapy) for severe allergies, including wasp, cat, house dust mite and birch pollen allergies
• IgG4 are thought to exert their anti-inflammatory effect through competitive binding with IgE to the allergen, thereby preventing formation of IgE immune complexes and IgE-mediated activation of mast cells.

Serum IgG4 level has been described to be the most sensitive and specific laboratory test for the diagnosis of IgG4-Related Disease (IgG4-RD) (2)

• recognized that an elevated serum IgG4 level can be encountered in other diseases such as pancreatic cancer, atopic diseases, and infections
• also note that serum IgG4 level is elevated in up to 5% of the normal population

Reference:

• Trampert DC et al. On the role of IgG4 in inflammatory conditions: lessons for IgG4-related disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2018; 1864 (4):1401-1409
• Ryu JH et al. Spectrum of Disorders Associated with Elevated Serum IgG4 Levels Encountered in Clinical Practice.International Journal of Rheumatology Volume 2012, ID 232960, doi:10.1155/2012/232960.