Study Explores Circulating Biomarker Profiles of Patients With Atopic Dermatitis

Jared Kaltwasser

Existing research has focused on skin symptoms, but a new study looks for alterations in the blood associated with moderate-to-severe atopic dermatitis.

A new study is helping to clarify the inflammatory profiles and systemic disease heterogeneity among patients with atopic dermatitis (AD).

The report, which examined blood biomarkers of patients with moderate-to-severe AD, was published in the journal Experimental Dermatology.

AD pathology is only partly understood. Several immune pathways, including Th2, Th22, Th1, and Th17 have been linked with the disease, but corresponding author Jonathan T. Sims, PhD, and colleagues, noted that it is not clear whether epidermal barrier dysfunction is the primary or secondary driver of AD.

Many previous studies have characterized the skin inflammation of AD, but the investigators said few studies have looked at alterations in blood. Those that have were limited in size and scope.

Sims and colleagues decided to fill the research gap by characterizing the circulating inflammatory profiles of patients with AD. They used blood samples from 123 patients who were enrolled in the phase 2 study of the oral Janus kinase 1 and 2 (JAK1/JAK2) inhibitor baricitinib (Olumiant) and evaluated 131 markers using high-throughput and ultrasensitive proteomic platforms. For comparison’s sake, the investigators also used a publicly available dataset of 58 patients with 73 markers as a validation cohort. All of the samples were taken from adults who had moderate to severe AD.

The analysis revealed “remarkably similar” blood biomarker profiles, Sims and colleagues said. Analyses of the baricitinib patients suggested 2 patient subgroups, a high-inflammatory subgroup that had elevated pro-inflammatory mediators, such as tumor necrosis factor (TNF)β, monocyte-chemotactic protein (MCP)-3, and interleukin (IL)-13, and a low-inflammatory subgroup that had lower levels. The findings were validated using the publicly available data cohort. Patients in the high-inflammatory group tended to have greater baseline disease severity and higher scores on a number of symptom indexes, including the Eczema Area and Severity Index.

“It was remarkable that diverse pro-inflammatory profiles spanning the Th-cell landscape were similarly elevated in the high inflammatory subgroup compared with the low inflammatory subgroup in both cohorts,” Sims and colleagues wrote. “It appears the primary distinction between the subgroups is a matter of intensity rather than large qualitative differences.”

The authors said this finding supports earlier research suggesting differences in symptom severity are based on a continuum of similar disease mechanisms, rather than distinct immune response characteristics. Notably, the presence of topical corticosteroids did not influence inflammatory profiles.

The investigators also looked at the impact of patient characteristics on biomarkers. They found all patients of Asian ethnicity had high immunoglobin E (IgE) levels. The study also found that African American patients were predominantly in the high inflammatory subgroup and also had higher baseline disease severity.

Sims and colleagues noted a number of limitations to their study, including a limited clinical annotation for the patients in the study and the fact that the study was focused only on peripheral blood.

Still, they said their research contributes important data about protein mediators and inflammation in AD.

“Overall, these data support a systemic inflammatory state accompanying the visible lesional inflammation typically seen in adult AD,” the investigators concluded. “These data will be useful for researchers with interest in broadly applying their findings in highly heterogeneous disease, including moderate-to-severe AD.”

Reference:

Sims JT, Chang C, Higgs RE, et al. Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate-to-severe disease. Exp Dermatol. Published online May 18, 2021. doi:10.1111/exd.14389