New research has found that mild or limited atopic dermatitis (AD) does not trigger systemic immune activation, and that therapies that target T-helper 2 might be effective against milder forms of the disease.
AD can affect up to 1 in 10 adults, but the large majority of such cases are mild or limited in nature. Despite this, the majority of research into the disease has focused on moderate to severe cases, yielding the insights that the disease involves epidermal barrier dysfunction, enhanced T-helper 2 and 22 (TH2/TH22) immune responses, and systemic immune abnormalities.
What was not clear was whether such systemic factors were at play even in mild forms of the disease. Corresponding Emma Guttman-Yassky, MD, PhD, of the Icahn School of Medicine at Mount Sinai Hospital, and colleagues, explained what they found when they investigated mild and limited AD specifically.
To learn more about the disease, the authors conducted cellular and molecular profiling of lesional and non-lesional skin and proteomic analyses of the blood of 61 patients with varying severities of the disease, as well as 20 healthy controls.
The authors found that cellular markers of epidermal hyperplasia and T-cell/dendritic cell infiltration were increased in the tissues of all of the patients with AD, regardless of the severity of the disease. Downstream mediators related to T-helpers 2, 22, 1, and 17 appeared to increase as the severity of a patient’s case increased, and were noted in both lesional and non-lesional skin.
TH2 and TH22 cytokines were elevated in lesional and non-lesional skin in all patients with AD, regardless of severity, but patients with mild or limited AD only had elevated TH1 and TH17 markers in lesional skin.
“Treg-related mediators (IL-10, FOXP3) were comparably up-regulated in all groups, without displaying the severity-based gradient in other immune axes,” Guttman-Yassky and colleagues wrote. “Unsupervised clustering aligned samples along a severity spectrum, where non-lesional mild/limited AD skin clustered with healthy controls.”
The investigators added that patients with moderate and severe AD had increases in T-helper-related and atherosclerosis/cardiovascular risk proteins, but such differences were not noted in the patients with mild or limited AD.
Guttman-Yassky and co-authors said the consistency of Treg expression even as TH2 activity increased with disease severity “suggests that compared to moderate and severe AD, mild/limited AD may be preferentially skewed toward a state of immune tolerance, with greater Treg-mediated suppression of pathogenic TH2 amplification.”
The authors noted that Tregs have been shown to have the ability to convert to TH2 cells.
“One possibility is that the mild/limited AD microenvironment may promote conversion from activated T-cells to Treg cells, although this hypothesis requires further testing,” they said.
In terms of treatment, the authors said the current treatment paradigm of topical agents often are not effective in the long-term. They said their new insights about prominent TH2 activation without systemic inflammation in patients with mild/limited AD suggests that targeting TH2 might help patients and lower the rate of relapse.
The authors noted some limitations, including a study population that was primarily comprised of European Americans and an inability to assess immune and barrier markers over a longer time frame.
Still, they said their study adds important data to our knowledge of mild and limited cases, information that could help limit the disease burden in this patient population.
The study, “Mild atopic dermatitis lacks systemic inflammation, and shows reduced non-lesional skin abnormalities,” was published online in Journal of Allergy and Clinical Immunology.