Gene mutation linked to persistent cow’s milk, egg allergy in children

Loss-of-function mutations in the filaggrin gene appeared to predispose children to multiple types of food allergies independently of whether they had eczema, according to study findings in The Journal of Allergy and Clinical Immunology.

These mutations also correlated with persistence of cow’s milk and egg allergy, results showed, suggesting the mutation has influence not only on development of allergy but also on the long-term disease course, according to Birgit Kalb, MD, of the Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin’s Clinic for Pediatric Allergy in the Experimental and Clinical Research Center, both in Berlin, and colleagues.

Filaggrin is an epidermal protein that is essential for the integrity of the skin barrier. Additionally, defective filaggrin has been linked to an impaired skin barrier and loss of natural moisturizing factor.

Therefore, loss-of-function (LOF) mutations in the filaggrin gene (FLG) represent the main genetic risk factors for eczema and are involved in the development of eczema-associated allergy airway diseases such as asthma and allergic rhinitis.

To better understand the connection between FLG LOF mutations with food allergy, Kalb and colleagues recruited 890 children (male, 64.4%; mean age at diagnosis, 2.36 years) from the Genetics of Food Allergy Study. All of the patients had been previously diagnosed through double-blind, placebo-controlled food challenges.

Allergic comorbidities occurred in 91% of this patient population, with eczema being the most common at 82.9%. The most common food allergies were 55.6% to hen’s eggs, 39.1% to peanuts and 30.7% to cow’s milk. The most common allergic symptoms involved the skin (89%), the gastrointestinal tract (32.4%) and the respiratory tract (24.8%).

Kalb and colleagues noted that the pattern of comorbidities varied according to age, in which eczema was most common in early childhood (4 years or younger) with lower rates of asthma (6.7%) and hay fever (6.9%), whereas school-age children (6 to 8 years) had higher rates of asthma (37.4%) and hay fever (42.3%).

Researchers genotyped the children for the most common FLG LOF mutations found in European populations — p.Arg501Ter, p.Ser761CysfsTer36, p.Arg2447Ter and p.Ser3247Ter — and found the frequency of these four alleles among children with food allergies to be 13.3%.

Results showed a significant association between FLG status and food allergy (OR = 2.8; 95% CI, 2.16-3.62) that was not restricted to specific foods.

Because filaggrin is linked to eczema, which is in turn linked to food allergy, researchers next tested whether the association they found was due to the presence of eczema.

However, after adjusting for eczema status, they found that the effect of the FLG mutations on food allergy decreased slightly but remained significant (adjusted OR = 2.1; 95% CI, 1.59-2.77), indicated that the mutations correlated with a risk for food allergy independent of eczema.

Further, results of a survival analysis of carriers vs. noncarriers of the FLG mutation showed significant differences in the curves for hen’s egg (P = .032) and cow’s milk (P < .0001) allergy, with carriers of the FLG LOF mutation more likely to experience persistent disease.

“The main separation of the curves occurred between 2 and 4 years, with minor increase of the deviation thereafter,” the researchers wrote, adding that their results also showed the presence of eczema or additional food allergies did not impact persistence of egg and cow’s milk allergy.

However, FLG LOF mutations did not appear to affect the severity of allergic response to hen’s egg or cow’s milk. Researchers also did not find a difference in IgE levels between carriers and noncarriers of FLG mutations.

Overall, FLG LOF mutations may be potential prognostic markers in the persistence of food allergy, the researchers wrote.

“This study does not only highlight the role of the impaired barrier in the development of any food allergy, it also demonstrates its impact on the long-term disease course,” they wrote. “Hence, FLG LOF mutations should be considered when planning oral food re-challenges.”