Immunoglobulins: IgG

Optimal Takeaways

Immunoglobulin G is the most abundant immunoglobulin in circulation and is divided into four subclasses: IgG1, IgG2, IgG3, and IgG4. Most IgG antibodies protect against pathogens. However, IgG4 antibodies block IgE-mediated reactions to food and increase tolerance to that particular food. Food-specific IgG antibodies in the blood may reflect increased GI inflammation and permeability, allowing partially digested food to pass through into the bloodstream and trigger an immune response.

Standard Range: 600 - 1640 mg/dL (6.00 - 16.40 g/L)

The ODX Range: 700 - 1600 mg/dL (7.00 - 16.00 g/L)

Low IgG can occur with leukemia, non-IgG multiple myeloma, hypoproteinemia, agammaglobulinemia, AIDS, immune deficiency, and immunosuppression (Pagana 2021). Lower levels of IgG may be seen with smoking and moderate alcohol intake, and levels tend to be higher in females than males (Gonzalez-Quintela 2008).

High levels of IgG can occur with chronic liver disease, autoimmune disease, granulomatous infection, hyperimmunization, IUD use, and monoclonal IgG-type multiple myeloma (Pagana 2019). Levels of IgG can increase with age, and higher levels can be seen with high blood pressure (Gonzalez-Quintela 2008).

Overview

IgG antibodies are the most abundant in the blood, accounting for 75% of all serum immunoglobulins (Pagana 2021). Total IgG comprises IgG1, IgG2, IgG3, and IgG4. IgG1 and 2 are the primary subclasses most likely reflected in a low total IgG.

Decreased IgG can compromise immune protection from pathogens. Mild to moderate reduction in total IgG in adults is seen at a level of 300-600 mg/dL (3-6 g/L), significant reduction is seen at 100-299 mg/dL (1-2.99 g/L), and profound reduction is seen at levels below 100 mg/dL (1 g/L). If warranted, immunoglobulin therapy aims to maintain serum IgG above 600 mg/dL, with higher levels above 800 mg/dL for improved pulmonary outcome. Some individuals may have an IgG below 400 mg/dL (4 g/L) accompanied by deficient IgA or IgM in common variable immunodeficiency (Agarwal 2007).

As part of the secondary immune response, IgG1-3 antibodies activate the classical pathway of the complement system and assist in the cellular response to a pathogen. However, IgG4 antibodies do not activate the complement system. Instead, researchers emphasize that the presence of IgG4 food antibodies represents immune tolerance to food, not an allergic reaction. However, the body’s need to create food-specific IgG4 antibodies may reflect excess inflammation and increased permeability of the intestinal epithelium, which should be investigated and addressed (Gocki 2016).

IgG4 food-specific antibodies inhibit IgE-mediated hypersensitivity reactions, increasing tolerance to a particular food. In one study of oral peanut immunotherapy (progressive desensitization), significantly increased peanut-specific IgG4 levels correlated with a significant decrease in peanut-induced basophil response (Paranjape 2020).

References

Agarwal, Shradha, and Charlotte Cunningham-Rundles. “Assessment and clinical interpretation of reduced IgG values.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology vol. 99,3 (2007): 281-3. doi:10.1016/S1081-1206(10)60665-5

Gocki, Jacek, and Zbigniew Bartuzi. “Role of immunoglobulin G antibodies in diagnosis of food allergy.” Postepy dermatologii i alergologii vol. 33,4 (2016): 253-6. doi:10.5114/ada.2016.61600      

Gonzalez-Quintela, A et al. “Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities.” Clinical and experimental immunology vol. 151,1 (2008): 42-50. doi:10.1111/j.1365-2249.2007.03545.x

Justiz Vaillant, Angel A., et al. “Immunoglobulin.” StatPearls, StatPearls Publishing, 12 October 2021.

Maguire, G A et al. “Are there any clinical indications for measuring IgG subclasses?.” Annals of clinical biochemistry vol. 39,Pt 4 (2002): 374-7. doi:10.1258/000456302760042678

Olivera, Ana et al. “Editorial: Innate Cells in the Pathogenesis of Food Allergy.” Frontiers in immunology vol. 12 709991. 10 Jun. 2021, doi:10.3389/fimmu.2021.709991

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Paranjape, Anuya et al. “Oral Immunotherapy and Basophil and Mast Cell Reactivity in Food Allergy.” Frontiers in immunology vol. 11 602660. 14 Dec. 2020, doi:10.3389/fimmu.2020.602660

Vidarsson, Gestur et al. “IgG subclasses and allotypes: from structure to effector functions.” Frontiers in immunology vol. 5 520. 20 Oct. 2014, doi:10.3389/fimmu.2014.00520