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 (

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.


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.
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 - Mobile version:


  1. Anonymous12/16/2009

    My son is 2 this month and was diagnosed with a slew of protein allergies, to include cow's milk & soy, at 4 months old. After 2 months of an extremely exclusive diet I ceased breastfeeding and we had been giving him Similac Alimentum ever since - he still gets 3 8-oz servings a day, since he still cannot tolerate dairy or soy. We just found out about Neocate and have switched him to Neocate One+, to see if this helps with his atopic dermatitis, and I'm hoping it may better our chances for him outgrowing this allergy by age 3!?!? Perhaps that's wishful thinking. If any milk or dairy product, to include goat's milk or cheese, comes in contact with his skin he immediately breaks out in hives in the immediate area, and touching/scratching it, spreads it to other areas. Most often one or both of his eyes will swell up. Cold water compresses and Benadryl help...thank goodness we've never had to use the EpiPen, though we keep one on hand just in case. Does anyone have a child who presented similarly and eventually OUTGREW IT??? We have NOT had any blood tests done so I do not know his levels, as mentioned in this article. Also, we now have a 2-month old baby girl who cannot even tolerate the Similac, her milk allergy is even worse than his, and is on Neocate now as well. Both will be seen by a new Allergist/Immunologist at the end of the month/year. I'm looking for ANY input/insight/recommendations and/or support!!! The allergies and my son's restricted diets, not being able to breastfeed my children, are & have been really difficult for me to deal with. Thank you!!!

  2. Anonymous12/16/2009

    Re: "My son is 2 this month and was diagnosed with a slew of protein allergies."

    Most (all?) food allergies are due to protein - not to carbohydrates or lipids.

  3. Anonymous12/16/2009

    my 4 year old (soon to be 5) has had routine blood tests and at about between 3 and 4 years old we were told his blood test look like he might have outgrown the milk allergy.... he thinks he is going to die if he goes for a milk challenge, so we have yet to do that..... but, he was the same way, hives from just contact and if he rubbed his eyes they would swell and turn red/bloodshot. FAAN is a great website and they have a facebook page as well. My son has other allergies as well, but at age 2 was found to have celiac and once we got him on that diet no longer had the dermatitis, so the food allergies may be the cause of his dermatitis, but don't rule out other. And the blood test are good to have, so you have a baseline and it can be tracked to see if the allergy is being outgrown.

  4. Anonymous12/16/2009

    Milk allergy is typically outgrown by college age - in around 80% of cases.

  5. Anonymous12/17/2009

    As the mother of 2, a 13 year old daughter allergic to dairy, shrimp, & misc. environmental allergies and a 10 year old daughter with a peanut allergy my heart goes out to you. Hang in there, get a full RAST test for each child, and know that you will be able to feed your children. I didn't even cook before I had kids, but I've learned and we've made it this far, you will too. Also, look for a food allergy support group near you - the first diagnosis and learning how to help your children early on is the toughest, it will get better.

  6. Anonymous12/17/2009

    I have 2, a four year old who is allergic to peanut and a 2 year old who can not tolerate milk protein. She too wa on Neocate and still remains drinking it. We are now in the challenging stage and is very nerve-wrecking. But as long as you know how to handle the situation if she were to start with the vomiting and/or diarrhea then by all means challenge them. Obviously the pediatricion or Gastroenterologist need to be the ones instructing you the parent. I'm happy to say after many weeks of yogurt challenges (1 spoonful per day for one week then increase by one every week after that until can tolerate entire yougurt in one shot). She is now also eating pizza, cream cheese, mac n cheese). After the holidays I will fo through the ultimate challenge: whole milk. I was told she would maybe outgrow this by the time she was 3 and here we are now at 2 where she is tolerating dairy without dehydrating.

  7. Anonymous12/17/2009

    Re: "get a full RAST test for each child, and know that you will be able to feed your children"

    A positive ImmunoCAP ("RAST") test does not mean clinical sensitivity (allergic reaction). Only proper history and food challenge conducted by an allergist can determine this.

  8. Anonymous12/22/2009

    I have a 4 yr old and a 2 yr old, both with severe multiple food allergies. My 4 year old is allergic to milk, eggs, peanuts, tree nuts, sesame and some fruits. My 2 yr old is allergic to milk, eggs, peanuts, wheat and certain fruits and vegetables. I too have a VERY hard time feeding them. Most of my time is consumed in the kitchen...and I'm no Betty Crocker! Each year I look forward to signs showing the dissappearance of these food allergies, but none yet. I know three is the lucky number for outgrowing some allergies, but let's go 5!!!

  9. Anonymous12/22/2009

    Re: "I know three is the lucky number for outgrowing some allergies, but let's go 5!!!"

    There is no lucky number.... :) They likely need a food challenge by an allergist.

  10. Anonymous1/06/2010

    I have a son 6 1/2 years old who is severely allergic to animal milk proptein, Casein with very high IgE levels are (nearly 1000 plus). He has had this since he was four months old. We have had tests done both for Total IgE and Specific Allergen - Milk protein, about three to four times in the past two years and they continue to be high. We are maintaining a strict avoidance diet and have never had the courage to challenge him with milk. His last episode was in Jan 2006. However, he is tolerant to Soya milk, which is a great relief. Initially his skin was very sensitive to milk but that has reduced now. However, that has made our task of checking any food item for unsuitability that much more difficult. We are still hopeful of him outgrowing the allergy. He also develops a wheeze, either exercise induced or due to dust and pollutants. We keep an EPIPEN Jr in hand at all times but thankfully have never had the occasion to use it. Looking forward to any solution/remedy that might come your way. He is OK with all other types of food including egg. We do not consume meat of any kind.

  11. Anonymous2/23/2011

    My son, who will turn 6 in April is severely allergic to dairy(milk) and dairy products. He has been allergic to milk since the day he was born. We have used Epipen and have had several trips to ER. His reaction to dairy is very severe, he gets anaphylaxis immediately that we have to rush him to ER. We have been hoping so long that he will overcome, but he is turning 6 now and still there is no change. We are looking for some information from research/study on what are the chances of him outgrowing his allergy.