A COMPREHENSIVE, new study has provided an analysis of systemic immune dysregulation across multiple inflammatory skin diseases. The research used high-throughput proteomic profiling to examine blood samples from patients with alopecia areata (AA), atopic dermatitis (AD), psoriasis, hidradenitis suppurativa (HS), and vitiligo, alongside healthy controls.
While prior research has largely focused on local skin pathology, this study highlights how these conditions also produce widespread systemic changes. Serum from 143 patients across the five conditions and 49 matched healthy controls was analysed using an OLINK multiplex assay. Proteins that were differentially expressed compared with controls were identified, and correlations between biomarkers and disease severity scores were assessed.
Blood Proteomics Reveals Systemic Immune Dysregulation
Results revealed both shared and disease-specific patterns of immune activation. HS exhibited the greatest systemic dysregulation, followed by AA, AD, psoriasis, and vitiligo. HS and psoriasis shared significant overlap in dysregulated proteins, particularly those involved in T-cell activation and migration (IL-2RA, CD40LG), innate immunity (IL-6, CXCL8/IL-8), and Th1/Th17 pathways (TNF, IL-17A, CXCL9/10, IL-20, CXCL1, LCN2). AA and AD were characterised by upregulation of general inflammatory markers (MMP12), T-cell activation signals (IL-15, IL-16), Th1 (IFNGR1, CXCL10), Th2 (IL-4R, CCL26, CCL27), and Th17/22 cytokines (IL-19, IL-20, PI3). Notably, HS patients also showed increased cardiovascular- and atherosclerosis-related proteins (PDGFA, SELP, MMP9), suggesting systemic comorbid risk.
Importantly, many of the biomarkers correlated with clinical severity scores, including SALT, SCORAD, PASI, and IHS4, confirming their relevance to disease burden.
Implications for Cross-Disease Therapeutic Strategies
The findings demonstrate the systemic nature of inflammatory skin diseases and suggest that overlapping immune pathways could be targeted therapeutically across multiple conditions. The study also emphasises the need for clinicians to consider whole-body immune activation, rather than focusing solely on skin lesions.
By revealing both shared and distinct immune profiles, this large-scale proteomic analysis paves the way for more precise biomarker development and the exploration of unified treatment strategies for patients with inflammatory dermatoses.
Reference
Glickman JW et al. Large-Scale Blood Proteomic Analysis Across Different Inflammatory Skin Conditions Reveals Extensive Immune Dysregulation With Distinct Biomarker Profiles. Allergy. 2025; doi:10.1111/all.70157
