Ancestry-associated immune signalling differences in atopic dermatitis and dupilumab treatment

BackgroundAtopic dermatitis (AD) is a common atopic disease worldwide and dupilumab, a monoclonal antibody directing to the IL4/IL13 signalling, is emerging as an effective therapy for AD. Recently, there is report describing differences in AD severity and treatment responses to dupilumab among different geographic regions, but the underlying mechanisms remain unresolved. Patients ancestral backgrounds represent one of the key differences among various geographic areas. Their implications in variability regarding diseases and treatment responses are gaining more and more recognitions. MethodsWe aimed to delineate the potential ancestry-associated differences in AD and treatment responses to dupilumab. We thoroughly surveyed Gene Expression Omnibus (GEO) for transcriptomic dataset in the context of AD and dupilumab treatment involving individuals of diverse ancestral backgrounds and carried out comparative analyses for samples from different ancestral groups. ResultsOnly one transcriptomic dataset was found for biopsy specimens from lesion and non-lesion skin from AD patients of self-reported White and Asian ancestral backgrounds. Despite comparable clinical phenotypes, Gene Set Enrichment Analysis revealed that skin samples from White AD patients exhibited upregulated IL4 & IL13 signalling from baseline to up to 4-week post dupilumab treatment, relative to Asian ones. ConclusionsThis is the first study of its kind to unravel the ancestry-related differences in AD and dupilumab treatment responses. These findings might be instrumental to future clinical patient stratification, risk assessment and guide personalized medicine treatment options for dupilumab.