Atopic dermatitis in children show high endotype heterogeneity

Paediatric atopic dermatitis (AD) shows four distinct clusters of serum biomarker profiles, only one of which shows marked similarity to adult biomarker clusters, a recent study has found.

“The identification of endotypes driven by distinct underlying immunopathologic pathways might be useful to define paediatric patients with AD who are at risk of persistent disease and may necessitate different targeted treatment approaches,” the researchers said.

The study included 240 children (aged 0–17 years) with AD in whom Luminex multiplex immunoassays were used to quantify 145 different serum biomarkers. Principal component analysis was performed to identify biomarker clusters, which were then compared against those previously identified in adults.

Four distinct biomarker clusters emerged. Cluster 1, the largest (41 percent of the total population), was characterized as the Th2 cell/retinol-dominant cluster, showing the highest levels of the acute-phase retinol binding protein-4, along with higher levels of Th2 cytokines (ie, interleukin [IL]-4, IL-5, and IL-13) and Th17 cytokines (IL-23 and IL-26) relative to clusters 2 and 4, but lower than those in cluster 3. Eczema Area and Severity Index score was lowest in this cluster.

Cluster 2 comprised 31 percent of the patients, who showed notably more severe AD than in other clusters (p<0.001). Apelin and markers associated with skin homing were highest in this cluster, along with the lowest levels of markers related to tissue remodelling and angiogenesis. Defined as skin-homing-dominant, cluster 2 also showed the highest rates of food allergy. This was the only cluster with a similar biomarker profile to adult AD.

Cluster 3, including 18 percent of study participants, was uniquely characterized as having the highest levels of markers associated with the Th1 markers. These included IL-2, IL-12, and interferons alpha and gamma, among others.

Meanwhile, cluster 4 had the lowest percentage of participants and lowest incidence of food allergy. Cluster 4 had the lowest levels of markers associated with the Th1 pathway, eosinophil trafficking, neutrophil activation and trafficking, and T-cell activation and skin homing.