Corneum Lipid, Cytokine Profiles at 2 Months Predict AD Onset in Children

Corneum lipid and cytokine biomarkers collected at age 2 months may predict atopic dermatitis (AD) onset at age 2 years, according to study results published in Journal of Allergy and Clinical Immunology.

Researchers recruited infants (N=111) born at Samsung Medical Center in South Korea and their parents for this study. The infants were stratified into at-risk (n=74) and control (n=37) groups based on a parental survey about family history of allergic rhinitis, skin prick tests (SPT) for allergens, and physician-diagnosed AD. Skin tape strips (STS) were collected from the infants at age 2 months. Protein and lipid levels were compared with AD diagnosed using the SCORing Atopic Dermatitis (SCORAD) scores at age 2 years.

The at-risk and control cohorts comprised 51.9% and 60.0% boys, 44.6% and 32.4% were born by cesarean delivery, and 2.7% and 10.8% were born preterm, respectively.

At age 2 years, 29.7% of the at-risk group and 13.5% of the controls were diagnosed with AD (P =.060).

At age 2 months, the participants who ultimately developed AD had significantly higher thymic stromal lymphopoietin (TSLP) levels than those who did not develop AD (P =.0032).

Overall, the level of TSLP at age 2 months strongly predicted AD onset by age 2 years of age (odds ratio [OR], 4.1; 95% CI, 1.7-10.1) and when combined with family history of atopic diseases, the predictive power increased (OR, 6.0; 95% CI, 2.3-15.8).

The AD group also had significantly elevated interleukin (IL)-13 (P <.0001) but not IL-4 (P =.6057) levels, which are both induced by TSLP and are considered to be main drivers of AD. Furthermore, TSLP strongly inhibited transcription of arachidonate lipoxygenase 3 (P <.0001) and arachidonate 12-lipoxygenase, 12R Type (P =.024) among the AD group compared with controls.

The lipid profiles of infants who would develop AD were found to have lower levels of:

• Four protein-bound omega-hydroxy fatty acid sphingosine (OS) ceramides (all P ≤.0187) and 2 OS-ceramides with C20-sphingosine molecular species (both P ≤.0073);
• Higher levels of 4 fatty acid-containing nonhydroxy fatty acid sphingosine-ceramides with C18-sphingosine (all P ≤.0368), 3 unsaturated sphingomyelin molecular species (all P ≤.0347), and 1 esterified omega-hydroxy fatty acid sphingosine ceramides (P =.0045); and
• Differing ratios of short to long nonhydroxy fatty acid sphingosine ceramides (both P ≤.03).

In the multivariate analyses, there were 33 significant predictors for developing AD. The strongest predictor was the combination of family history, type 2 cytokines, and dysregulated lipids (OR, 54.0; 95% CI, 9.2-317.5; P <.001).

The major limitation of this study is the small sample size.

Study authors conclude, “More studies using new cohorts of children of different ethnicities are needed to replicate current findings and to confirm if found new lipid biomarkers are unique for Asian children or are common for children of all ethnical groups. The noninvasive method of stratum corneum collection using STS is safe to use even on the skin of newborn children that, together with a possibility to use targeted biologics, brings strong expectation that atopic diseases and the atopic march can be prevented.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.