How to predict who will "outgrow" food allergy to cow's milk: low specific IgE, high IgA and high IgG4
The development of tolerance in IgE-mediated allergies has been associated with:- lower cow's milk (CM)-specific IgE levels
- increasing levels of specific IgG4
- increasing IgA
This study investigated if specific antibody responses to CM proteins differ between:
- patients who recovered from cow's milk allergy (CMA) by the age of 3 years (early in life)- patients who developed tolerance only after the age of 8 years (later in life)
83 patients with IgE-mediated CMA were included.
Serum levels were measured for:
- IgE antibodies to cow's milk (CM)
- IgA, IgG1 and IgG4 antibodies to β-lactoglobulin and α-casein
Patients with persistent CMA at the age of 8 years had higher CM-specific IgE levels compared with patients who became tolerant by 3 years. They had lower serum IgA levels to β-lactoglobulin at diagnosis, and lower IgG4 levels to β-lactoglobulin and α-casein at follow-up.
The authors concluded that high cow's milk-specific IgE levels predict the persistence of food allergy.
On the other hand, development of tolerance is associated with elevated levels of β-lactoglobulin-specific IgA at the time of diagnosis, and later increasing specific IgG4 levels to β-lactoglobulin and α-casein.
It is important to note that in 10–25% of food allergy reactions, sIgE can be undetectable by blood test (http://buff.ly/1e7HAmY).
What is the most common food allergen in children?
(A) Gal d (egg)
(B) Tri a 19 (wheat)
(C) Mal d 1 (apple)
(D) Gly m (soy)
(E) Ara h (peanut)
(F) Bos d (milk)
(G) Api g 4 (celery)
Answer: F.
ImmunoCAP Immunoassay
The ImmunoCAP method was developed by Phadia. It utilizes a “sandwich” ELISA technique:
1. The ImmunoCAP sponge has allergen bound to it and serves as the first piece of bread ("bottom half").
2. Patient serum is added and specifc IgE to that allergen binds to the allergen on the sponge - this is the "meat" of the ELISA sandwich.
3. All of the unbound protein is washed away abd anti-IgE is added - this binds to the sIgE that was captured by the sponge in step two. The anti-IgE conjugate is the "second piece of bread" ("top half").
Allergen-specific IgE levels are not comparable between different laboratory methods - for example, ImmunoCAP vs. DPC Immulite 2000. Predictive values of specific IgE levels published in the literature for management of food allergies are based on studies using the ImmunoCAP assay. These predictive values cannot be applied to specific IgE levels from other assay systems.
8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).
Who will "outgrow" food allergy? It depends on the epitope
Each food is composed of many proteins and these proteins have multiple areas, termed epitopes, to which the immune system can respond. Epitopes that are dependent upon the folding of the proteins are called conformational epitopes. Epitopes that are not dependent upon folding are called linear epitopes.
A linear epitope oftens means a more prolonged allergy which is “stable” and persistent. A conformational epitope (egg, milk) often means a mild, transient allergy.
In children, 85% of cow’s milk, egg, wheat, and soy allergy resolves by five years. In contrast, only 20% of children “outgrow” their peanut allergy, and only 9% of tree nut-allergic patients do so.
References:
Duration of clinical reactivity in cow's milk allergy is associated with levels of specific immunoglobulin G4 and immunoglobulin A antibodies to β-lactoglobulin. E. M. Savilahti et al. Clinical & Experimental Allergy, 2009.
http://www3.interscience.wiley.com/journal/123197439/abstract
In children, casein-specific IgE linked to cow's milk allergy while IgG4 antibodies possibly linked to tolerance. Clinical and Molecular Allergy 2012, 10:1.
Image source: Wikipedia, GNU Free Documentation License.
Related books:
Milk allergy resolution calculator from CoFAR http://bit.ly/U6TkNS - Mobile version: http://bit.ly/U6TmFn