An antibody primer

Antigen-Specific Antibody Testing

Our food and inhalant sensitivity tests gauge the reactivity of antibodies known to be involved in hypersensitive reactions, including Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin G4 (IgG4), and Immunoglobulin E (IgE).  Below is more information on each of these antibodies and reasons to consider ordering a test.

Immunoglobulin A (IgA)

IgA comprises 70% of total antibodies in the body, and 14% of antibodies in blood. As a first line of defense, IgA operates mainly on epithelial surfaces, protecting mucosal tissues. It can be found in secretions like tears, saliva, sweat, and gastric fluid. Higher levels of specific IgA may be found in blood when mucosal barriers have been compromised. Like a vicious cycle, increased mucosal permeability can cause inflammation, while inflammation encourages increased permeability. IgA itself, however, does not activate the classical complement pathway nor trigger inflammation.

IgA facilitates the development of oral tolerance which enables our immune system to “stand down” when exposed to food antigens while eating. The breakdown of oral tolerance may result in the abnormal processing of food proteins in the gut resulting in pro-inflammatory food antigen handling. 

IgA has a circulating half-life of 6 days. Generally, complete avoidance of an offending antigen for at least 5-7 half-lives creates opportunity for a notable reduction in specific antibody concentration. For IgA, 7 half-lives is 42 days.

  • Mediates delayed hypersensitivity reactions; mucosal immunity
  • Symptom onset may occur within 3-4 hours to 3-4 days
  • Consider specific IgA testing when you know of or suspect increased mucosal permeability, inflammation, or food-related symptoms.

Immunoglobulin G (IgG)

IgG is the most abundant antibody in circulation and is primarily found in blood and extracellular fluid. Comprising 75% of total antibodies in blood, IgG mediates delayed hypersensitivity reactions. With symptom onset ranging from hours to days, IgG-mediated sensitivities can be difficult to correlate with their triggers in absence of testing.

IgG immune complexes, if not cleared, can deposit in the body’s tissues and cause inflammation. Additionally, most of the IgG subclasses (IgG1-IgG3) have the capacity to trigger an inflammatory cascade by activating complement. Conditions that have been associated with IgG-mediated food sensitivities include but are not limited to IBS, IBD, eczema, migraine, autism, anxiety, depression, and obesity.

IgG has a circulating half-life of 22 days. Generally, complete avoidance of an offending antigen for at least 5-7 half-lives creates opportunity for a notable reduction in specific antibody concentration. For IgG, 7 half-lives is 154 days, or almost 6 months.

  • Mediates delayed hypersensitivity reactions
  • Symptom onset may occur within 3-4 hours to 3-4 days
  • Order to uncover underlying food reactions that may be suspected by presence of symptoms.

Immunoglobulin G4 (IgG4)

Of the four IgG subclasses, IgG4 is the only one that does not fix complement and trigger inflammation. IgG4 may indicate tolerance and is produced from chronic antigen exposure, like that which occurs during antigen-specific immunotherapy (SIT). IgG4 may act as a “blocking” antibody to prevent more serious, IgE-mediated allergic events.

Testing for specific IgG4 adds value to the in-vitro diagnosis of allergies, as increasing evidence demonstrates the IgG4:IgE ratio increases according to the progress of specific immunotherapy (SIT). At 4% of total IgG subclasses, IgG4 testing provides additional insight into the level of inflammation instigated by specific IgG sensitivity.

Half-life details are the same as other IgG subclasses.

  • The only IgG subclass that does not trigger inflammation; may act as a "blocking" antibody.
  • Order test for additional insight into specific antigen sensitivity.
  • Order test to monitor progress of a specific immunotherapy program (SIT).

Immunoglobulin E (IgE)

IgE mediates immediate hypersensitivity reactions, known as a Type I allergic response. Symptom onset generally occurs within minutes to hours after exposure and can be life-threatening. IgE-mediated reactions usually affect the cardiovascular, respiratory, gastrointestinal, and/or integumentary (skin) systems. Examples include allergic asthma, urticaria, rhinoconjunctivitis, and anaphylaxis.

IgE is primarily found just beneath epithelial surfaces, bound to mast cells or basophils ready to release chemicals like histamine. IgE itself does not fix complement or trigger inflammation. Comprising only 0.03% of circulating antibodies, IgE is the least abundant antibody found in blood. Compounded by its short half-life of only 1-2 days in circulation, antigen-specific IgE may be undetectable in blood within days after exposure. Serum IgE testing is best for detecting reactions to exposure within days prior to collecting specimen.

  • Mediates immediate hypersensitivity reactions (Type One) 
  • Order test to assess reaction to regularly consumed foods.