Multimodal Integration of Protein Interactomes With Genomic and Molecular Data Discovers Distinct Rheumatoid Arthritis Endotypes

Our findings demonstrate the use of network-based approaches in revealing differential genetic risk factors underlying CCP+/RF+ and CCP-/RF+ RA. Disease-associated gene modules detected in synovial tissue were also observed in peripheral blood, indicating joint-specific molecular programs are reflected systemically. This cross-tissue concordance highlights the potential for blood-based assays to capture pathogenic mechanisms active in the joints, enabling practical patient stratification. Our findings highlight why patients with CCP+/RF+ and CCP-/RF+ RA exhibit distinct clinical courses and therapeutic responses, supporting precision-guided treatment strategy development in RA.