Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate‐to‐severe disease

xlomafota13 shared this article with you from Inoreader Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate‐to‐severe disease Via Experimental Dermatology ABSTRACT Background Atopic dermatitis (AD) is a heterogeneous systemic inflammatory skin disease associated with dysregulated immune responses, barrier dysfunction, and activated sensory nerves. Objective To characterize circulating inflammatory profiles and underlying systemic disease heterogeneity within AD patients. Methods Blood samples from adult patients (N=123) with moderate-to-severe AD in a phase 2 study of baricitinib (JAHG) were analyzed. Baseline levels of 131 markers were evaluated using high-throughput and ultrasensitive proteomic platforms, patient clusters were generated based on these peripheral markers. We implemented a novel cluster reproducibility method to validate cluster outcomes within our study and used publicly available AD biomarker dataset (73 markers, N=58 patients) to validate our findings. Results Cluster reproducibility analysis demonstrated best consistency for 2 clusters by k-means, reproducibility of this clustering outcome was validated in an independent patient cohort. These unique JAHG patient subgroups either possessed elevated pro-inflammatory mediators, notably TNFβ, MCP-3, and IL-13, amongst a variety of immune responses (high inflammatory) or lower levels of inflammatory biomarkers (low inflammatory). The high inflammatory subgroup was associated with greater baseline disease severity, demonstrated by greater EASI, SCORAD Index, Itch NRS, and DLQI scores, compared to low inflammatory subgroup. African American patients were predominantly associated with the high inflammatory subgroup and increased baseline disease severity. Conclusions In patients with moderate-to-severe AD, heterogeneity was identified by the detection of 2 disease subgroups, differential clustering amongst ethnic groups, and elevated pro-inflammatory mediators extending beyond traditional polarized immune responses. Therapeutic strategies targeting multiple pro-inflammatory cytokines may be needed to address this heterogeneity. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.