Enhanced Siglec-8 and HLA-DR and Reduced CRTH2 Surface Expression, Highlight a Distinct Phenotypic Signature of Circulating Eosinophils in Atopic Dermatitis.

Abstract

Atopic dermatitis (AD) as well as other type 2 immune response (T2) diseases are often linked to elevated eosinophil (Eos) levels in the blood. Although the role of Eos in AD pathophysiology is suspected, it remains unclear. The development of new treatments targeting the T2 response, particularly cytokines involved in Eos activation and chemotaxis, makes it necessary to identify potential Eos profiles in AD that may respond to these treatments. A prospective study was conducted comparing blood Eos phenotypes in moderate-to-severe AD patients (n=19) without recent systemic treatment to healthy individuals (HI, n=19). The primary outcome was the membranous phenotypic signature of Eos, assessed by flow cytometry. Most AD patients (84%) had early onset in childhood, a severe disease (mean SCORAD of 57.5), and elevated blood Eos counts (310 per µl in AD vs 120 in HI, p<0.0001). AD patients exhibited lower CRTH2 on Eos but higher levels of HLA-DR and Siglec-8 compared to HI. Other surface proteins showed no significant differences. Clustering analysis confirmed increased Siglec-8 in AD patients. Additionally, AD patients had higher serum levels of T2 immune response-markers as eotaxin-2, IL-5, IL-3, and TARC. Circulating Eos in AD patients show a distinct phenotypic profile, suggesting a role in AD pathophysiology and potential involvement in differential treatment responses.