Integrating metabolomic signatures and adaptive immune markers to clarify vitamin D signalling in keloid pathogenesis in dark-skinned South Africans

<p dir="ltr">This cross-sectional analytical study explored the relationship between vitamin D status, immune dysregulation, and metabolic alterations in keloid pathogenesis within a cohort of 102 dark-skinned South African individuals. Serum 25-hydroxyvitamin D [25(OH) D] levels were quantified via electrochemiluminescence and stratified into low (<20 ng/mL) and normal (≥20 ng/mL) groups. Clinical and demographic data were collected using structured tools, and disease severity was evaluated through the Detroit Keloid Scale. Immune profiling was conducted on a subset of 57 participants using bead-based multiplex immunoassays targeting cytokines, costimulatory molecules, and ligands relevant to adaptive immunity. For metabolic profiling, serum samples from 96 participants were analysed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS), with metabolite identification guided by the Human Metabolome Database. Due to non-parametric data distribution, Wilcoxon rank-sum and Kruskal–Wallis tests were employed, alongside Partial Least Squares–Discriminant Analysis (PLS-DA) for metabolomic clustering. Rigorous quality control measures were integrated throughout all laboratory and statistical processes. This multifaceted systems biology approach facilitated the integrated exploration of vitamin D, immune markers, and serum metabolites, offering novel insights into keloid pathogenesis in a genetically and environmentally unique population.</p>