Analytical standardization and inter-platform harmonization of immunoassay-based biomarkers in atopic dermatitis:...

Immunoassay-based biomarkers, including TARC/CCL17, IL-13, IL-22, IL-31, SCCA1/SCCA2, and periostin, have demonstrated clinical utility for severity assessment, therapeutic monitoring, and endotype classification in atopic dermatitis (AD). However, the translation of these biomarkers into routine clinical laboratory practice is critically hindered by the absence of analytical standardization and inter-platform harmonization. Multiple immunoassay platforms, including conventional ELISA, bead-based multiplex assays (Luminex), proximity extension assays (Olink), electrochemiluminescence (MSD), and ultra-sensitive digital immunoassays (Simoa), are employed across research and clinical settings. These platforms differ substantially in detection principles, antibody pairs, calibrator materials, sensitivity ranges, and output formats, generating results that are frequently non-interchangeable. This review systematically examines the analytical and preanalytical barriers to standardization of AD biomarker immunoassays within the framework of diagnostic laboratory medicine. We evaluate cross-platform concordance data, identify sources of inter-assay discordance, and analyze the current absence of commutable reference materials, external quality assurance (EQA) schemes, and consensus-based clinical decision thresholds for AD-specific analytes. Preanalytical challenges unique to novel sample matrices, including tape-strip sampling, microneedle-based skin fluid collection, and sweat analysis, are examined with respect to their impact on measurement variability. Age-specific and population-specific reference interval requirements are reviewed in the context of the known heterogeneity of AD across pediatric and adult populations and across ethnic groups. Finally, we propose a phased roadmap for achieving analytical harmonization, encompassing systematic method comparison studies, development of certified reference materials, establishment of dedicated EQA programs, multi-center reference interval studies, and integration with point-of-care and digital health platforms. This roadmap aims to bridge the gap between biomarker discovery and reproducible clinical laboratory reporting, thereby enabling the incorporation of standardized AD biomarker testing into precision dermatology workflows.