Skin tape strip tests at age 2 months indicate later risks for food allergy
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Key takeaways:
- Infants who developed food allergy had higher levels of N(C18S)-ceramides with unsaturated fatty acids.
- Omega-hydroxy fatty acid sphingosine ceramide levels were increased as well.
The use of a noninvasive skin tape strip at age 2 months can identify infants who are at risk for developing food allergy later, according to a study published in The Journal of Allergy and Clinical Immunology.
This early identification could trigger interventions to prevent or mitigate disease development, Donald Y.M. Leung, MD, PhD, division head of pediatric allergy and clinical immunology at National Jewish Health in Denver, and colleagues wrote.
“Currently, physicians take a family history to determine whether or not an infant is likely to develop a food allergy, but family histories do not predict food allergy in many cases,” Leung told Healio.
“Skin tape analyses give us a more precise quantitation of which lipids and cytokines are present in the skin, and certain combinations of lipids and cytokines increase the odds ratio to more than 100 of developing food allergy,” he continued.
Leung and colleagues collected skin tape strips from the forearms of 129 infants who did not have any signs of clinical food allergy or atopic dermatitis (AD) at age 2 months, followed by lipidomic analyses of these strips via liquid chromatography-tandem mass spectrometry and cytokine determination.
By age 24 months, nine of the infants had developed food allergy alone, nine others had developed AD with food allergy, and 28 had developed AD alone. Egg white was the most common allergy, reported in 16 of the 18 children with food allergy.
Compared with the infants who only developed AD and the infants who did not develop AD nor food allergy, the infants with food allergy had unique abnormalities in the lipids of their stratum corneum, including increased levels and proportions of N(C18S)-ceramides with unsaturated fatty acids and C18-sphingosine.
The levels and proportions of these unsaturated nonhydroxy fatty acid sphingosine ceramides (NS-ceramides) also were increased in the infants who developed both food allergy and AD. The infants who only developed AD did not see any such differences, indicating that these increases are unique to food allergy but not AD, the researchers wrote.
“The finding that there was a unique profile of lipids and cytokines in food allergy distinct from atopic dermatitis was surprising,” Leung said.
Food allergy often is found in combination with AD, he added, so it was assumed that the skin barrier abnormality in AD predisposed patients to food allergy.
“But the finding of two distinct skin barrier abnormalities in AD and food allergy indicate that each should be treated independently,” Leung said.
When Leung and colleagues combined the infants who developed food allergy alone with those who developed both food allergy and AD, the differences in these parameters compared with those with food allergy alone, AD alone, and no food allergy or AD were stronger.
The infants who developed food allergy additionally had increased levels of omega-hydroxy fatty acid sphingosine ceramides (OS-ceramides) compared with the infants who did not develop any food allergy or AD and with the infants who developed AD, who had decreased levels of OS-ceramides, the researchers wrote.
The skin of the children who later developed food allergy additionally had significant increases in levels of N32:0O-S-ceramides with all three sphingoid bases and total levels of protein-bound OS-ceramides compared with the children who later developed AD as well.
Further, the infants who later developed AD had increased unsaturated sphingomyelin species with 24:1 and 26:1 fatty acids, but the infants who later developed food allergy or food allergy with AD did not have these increases.
The infants who later developed food allergy, AD and both food allergy and AD all had equally elevated levels of TNF-alpha, IL-6, IL-13 and macrophage-derived chemokine, but their levels of IL-1-alpha and IFN-gamma-induced protein 10 were not elevated compared with those infants who did not develop any food allergy or AD.
The infants who later developed AD and who later developed both AD and food allergy had elevated levels of thymic stromal lymphopoietin (TSLP), but the infants who later only developed food allergy did not.
Also, the infants who later developed AD did not have elevated levels of IL-33, but the infants who later developed food allergy only had moderately elevated levels.
These levels were significantly higher (P < .05) among the infants who later developed both AD and food allergy, compared with those infants who did not develop any AD or food allergy and with the infants who only developed AD.
Again, when the infants who later developed food allergy were combined with those who developed both food allergy and AD, there was a complete separation from those infants who did not develop any food allergy or AD in terms of IL-33 levels.
Infants who developed both AD and food allergy had increases in TSLP and IL-33 levels. This upregulation in TSLP and IL-33 differentiates the infants who later developed food allergy, AD, and both diseases, the researchers said.
Regardless of future AD status, the researchers said that unsaturated NS-ceramide species and protein-bound OS-ceramides are strong predictors for food allergy. Also, they said, altered lipid profiles, IL-33 and TNF-alpha together substantially increased food allergy prediction possibilities, with an odds ratio greater than 100.
Odds ratios for food allergy with specific biomarkers at age 2 months included:
- 5.8 (95% CI, 1.9-18) for IL-33;
- 7.7 (95% CI, 2.5-23.6) for IL-13;
- 9.5 (95% CI, 2.8-32) for protein-bound ceramides;
- 11.3 (95% CI, 2.5-51.6) for TNF-alpha;
- 11.3 (95% CI, 2.5-51.6) for unsaturated NS-ceramides; and
- 101.4 (95% CI, 5.4-1910.6) for unsaturated NS-ceramides, IL-33 and TNF-alpha together.
Based on these findings, the researchers wrote that changes in the stratum corneum lipidome can predict later food allergy, with lipid and cytokine signatures also predicting both food allergy and AD.
With targeted biologics now available for TSLP, IL-4 and IL-13, with others under development for IL-33, Leung and colleagues wrote that potential therapies may be able to prevent and circumvent disease for infants whose skin strips indicate greater risk.
Early introduction of allergens into the diets of these infants may also be beneficial, Leung said.
“Many parents try to avoid the introduction of foods into babies’ diets, but reduction of food allergy requires the introduction of diverse foods into food allergy-prone babies to induce tolerance within first few months of life,” he said.
The researchers also called for additional studies including different ethnic groups conducted in different regions of the world to determine the universality of these molecular signatures.
“Confirmation of this research in other birth cohorts and making this test available to the general population are important next steps in this research,” Leung said.