Filaggrin Loss-of Function Mutations are Associated With Persistence of Egg and Milk Allergy

To test the association of filaggrin (FLG) loss of function (LOF) mutations with allergy to diverse foods and their effect on the persistence of early food allergies (FAs).

Children (n = 890) from the Genetics of Food Allergy study were recruited from 4 sites in Germany, of which 766 (86%) were diagnosed by oral challenge and 658 (86%) of those by double-blind placebo-controlled challenges. The remaining 124 children (14%) had convincing histories and serum specific IgE. Children from an earlier allergy study population for whom data of FA were not detailed and on whom challenges were not done served as controls.

Organ specific reactions and allergen specific IgE levels were documented as was presence or absence of eczema and asthma. Children were followed frequently from birth to 2 years old and then annually to age 13. Samples of whole blood were genotyped for the 4 most common FLG mutations and participants were stratified as carriers (homo- or heterozygotes) or noncarriers (wild type).

Hen’s egg (HE, 56%), peanut (39%), and cow’s milk (CM, 31%) were the most common FAs. Cutaneous reactions (94%) were more common than gastrointestinal (32%) or respiratory reactions (23%). Eczema (83%), asthma (23%), and allergic rhinitis (24%) were common comorbidities. FLG mutations were present in 211 (24%) children. FLG mutations were associated with FA (odds ratio = 2.80, P < .001) independent of specific foods except for wheat. After adjusting for eczema (of which FLG mutations are a major cause), the association of FLG mutations with FA was not substantially different. FLG LOF mutations were not associated with age at onset or organ specific FA reactions. Patients with CM or HE allergy and FLG mutations outgrew their allergies at a slower rate than those without (P < .001 and P = .04, respectively) and were less likely to outgrow their allergies by age 13 (P < .0001 and P = .032, respectively). Furthermore, those who did not outgrow CM or HE allergy were more likely to carry FLG LOF mutations than those who did outgrow their allergies. FLG mutations were not correlated with severity of FA reaction.

FLG LOF mutations are associated with FA independent of eczema and increase the risk of persistent CM and HE allergy.

FLG is essential to the integrity of epithelial barrier function. LOF mutations are the primary risk for atopic dermatitis (AD) and increased transepidermal water loss. In the context of AD, mutations are also associated with allergic sensitization in asthma and allergic rhinitis. It is now clear that FLG LOF is associated with FA as well, yet independently of AD. Furthermore, FLG LOF mutations are a risk for persistent FA. Although this study population was pretty homogeneous, the authors point out that FLG mutation frequency does not seem to vary much by ethnicity. It is not known if specific mutations convey greater risk for FA and its natural history. More research is necessary to better understand how much FLG contributes to the genetic basis of how the atopic diseases related to one another.