Beyond the Shared Inflammatory Axis: Differentiating Molecular Signatures in Psoriatic Arthritis and Ankylosing Spondylitis through Integrated Omics

Spondyloarthropathies (SpA), which include ankylosing spondylitis (AS) and psoriatic arthritis (PsA), are inflammatory rheumatic diseases with overlapping clinical and immunological characteristics but distinct molecular mechanisms. This study aimed to compare transcriptomic signatures of AS and PsA by investigating differentially expressed genes and associated regulatory pathways. Four public RNA-Seq datasets from GEO (GSE186063, GSE117769, GSE205748, and GSE221786) were used. Using an integrative strategy involving scientific text mining, functional enrichment, and biological curation, 433 genes with potential relevance to both conditions were selected. Based on this set, differential gene expression (DEG) analyses were performed, protein-protein interaction (PPI) networks and gene regulatory networks (GRN) were constructed, and hubs and master regulators (MRs) were identified. The integration of these approaches allowed the identification of shared inflammatory pathways, especially related to the IL-23/IL-17 axis, as well as disease-specific signatures. Functional analysis revealed enrichment in Th17 cell differentiation processes, lipopolysaccharide response, and activation of classical inflammatory pathways. This study provides a comprehensive comparative view of the transcriptomic signatures of PsA and AS that point to potential biomarkers and distinct therapeutic targets.