Uncover Food-Related Immune Reactions
The Allergix IgG4 Food Antibody Profile is a blood test that measures IgG4 antibodies to 90 commonly consumed foods.
When should testing for IgG4 Food Antibodies be considered?
Circulating IgG4 food antibodies are not diagnostic for a specific
condition but indicate an immune response to the presence of food
antigens. IgG4 antibodies are produced in a delayed hypersensitivity
reaction, which can occur one to seven days after exposure to the
offending food antigen. These reactions are difficult to detect since
there may be no obvious association with the offending food. Commonly
reported symptoms for elevated IgG4 responses involve GI tract, skin,
nose, and throat. In contrast, the immune response could be a normal
response that would not necessarily cause symptoms. Therefore, test
results should always be viewed in the context of the overall clinical
Conditions associated with IgG4 food antibodies
- Eosinophilic esophagitis1-3
- Irritable bowel syndrome/ GI symptoms4,5
- Crohn's disease6
Of the 5 classes of antibodies, immunoglobulin G (IgG) is the most
abundant circulating antibody, making up 75% of antibodies. The other
classes of antibodies include IgE, IgA, IgM, and IgD. IgG has 4
subclasses including IgG1, IgG2, IgG3, and IgG4 making up 66%, 23%, 7%,
and 4% of the IgG antigen pool respectively.
IgG4 is unique compared to the other subclasses. It acts as a
blocking antibody to the allergy-producing IgE antibody, and with the
IgE antibody, is considered part of the Th2 response. Increases in IgG4
levels correlate with improved clinical responses since it blocks the
IgE anitbody allergic response; it is involved in establishing
immunologic tolerance to that food. IgG4 does not activate complement
compared to IgE3.7 Some speculate that IgG4
may be produced initially to attenuate IgE-mediated disease, but
ultimately results in a pro-inflammatory process in susceptible atopic
What advantage does the IgG4 Food Antibody test offer compared to other diagnostics?
IgG food antibodies can result in a delayed symptom response to a food.1
Whereas IgE antibodies can result in immediate-hypersensitivity to a
substance. It is generally easier for patients and clinicians to
identify a food that causes an immediate response. A delayed-response to
food may be more challenging to determine, and testing can be helpful.
The IgG Food Antibody Assessment
evaluates total IgG (1-4) versus only testing for IgG4 and offers a
more complete assessment. Clinicians may consider measuring IgG4 in
patients with eosinophilic esophagitis.
IgG4 is an allergy blocking antibody, however, scientific societies
do not recommend its use in the diagnosis of food allergy. IgG4 testing
cannot be substituted for IgE blood testing or skin prick testing for
Other types of adverse food reactions that are not mediated by the
immune system are referred to as food intolerances. Food intolerances
include lactose intolerance due to lactase enzyme deficiency in the gut;
testing is available for suspected lactose intolerance.
Testing is not available for all food intolerances. These include
vasoactive amines like histamine and tyramine, food additives and
preservatives (nitrites, sulfites, MSG, aspartame), salicylates,
nightshades, lectins, FODMAPs, oxalates, etc. Since testing is not
available for every type of adverse food reaction, the
elimination/rechallenge diet remains the gold standard for
identification of symptom-producing foods.
Genova's Allergix IgG4 antibody test is designed for the semi-
quantitative measurement of human IgG4 in serum to 90 different foods
using an indirect ELISA (enzyme linked immunosorbent assay). The ELISA
test, developed by Genova, utilizes a blocking agent to reduce the
occurrence of nonspecific antibody antigen interactions. The reported
results of the test give each food a numerical value that is ranked from
negative to severe.
What can clinicians and patients expect from IgG Food Antibody testing?
In general, clinical management of the patient with food
sensitivities involves elimination or rotation of the highly reactive
food(s). Often times, clinicians and patients notice improvement of
symptoms after diet modification. Patients may be able to tolerate the
food in small amounts, without symptoms, after several weeks or months
Please visit our IgG, IgE, and Celiac Tests Prep page
prior to ordering the test to learn about medications that may impact
test results, length of exposure to antigens, pediatric testing, and
diseases that may affect antibody levels.
- Weidlich S, Nennstiel S, Jesinghaus M, et al. IgG4 is Elevated in
Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease
Patients. Journal of clinical gastroenterology. 2019.
- Clayton F, Fang JC, Gleich GJ, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology. 2014;147(3):602-609.
- Schuyler AJ, Wilson JM, Tripathi A, et al. Specific IgG4
antibodies to cow's milk proteins in pediatric patients with
eosinophilic esophagitis. The Journal of allergy and clinical immunology. 2018;142(1):139-148.e112.
- Zar S, Mincher L, Benson MJ, Kumar D. Food-specific IgG4
antibody-guided exclusion diet improves symptoms and rectal compliance
in irritable bowel syndrome. Scandinavian journal of gastroenterology. 2005;40(7):800-807.
- Bernardi D, Borghesan F, Faggian D, et al. Time to reconsider the clinical value of immunoglobulin G4 to foods? Clinical chemistry and laboratory medicine : CCLM / FESCC. 2008;46(5):687-690.
- Rajendran N, Kumar D. Food-specific IgG4-guided exclusion diets improve symptoms in Crohn's disease: a pilot study. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2011;13(9):1009-1013.
- Gocki J, Bartuzi Z. Role of immunoglobulin G antibodies in diagnosis of food allergy. Postepy dermatologii i alergologii. 2016;33(4):253-256.
- Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. The Journal of allergy and clinical immunology. 2016;138(4):1190-1192.e1193.