Although systemic autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, etc.) and metabolic diseases (such as gout, hyperuricemia, etc.) have different clinical manifestations, they exhibit significant comorbidity in epidemiology, and genetic studies have revealed shared risk loci, suggesting that they may be rooted in a common “soil” of immune metabolic dysregulation. However, clinically, patients often present with only a single disease or a unique combination of complications (such as systemic sclerosis with interstitial lung disease), showing significant pathological heterogeneity.
Current research mostly focuses on single diseases in isolation, failing to systematically resolve the following core contradictions: 1) Which molecular pathways truly constitute the “common soil” across diseases, rather than merely phenotypic associations? 2) Under the same genetic background, what are the specific molecular events driving patients to develop different disease manifestations? 3) How can we identify high-risk subgroups prone to developing fatal complications (such as interstitial lung disease) from shared mechanisms?
Based on this, we propose a dual-track strategy of simultaneously and systematically exploring “common framework-specific pathways”:
Common molecular framework research aims to identify pleiotropic genes and core pathways (such as type I interferon signaling and inflammasome activation) influencing the risk of multiple diseases, revealing the biological basis of comorbidities; heterogeneous specific pathway research focuses on identifying unique molecular tags driving disease differentiation (such as fibrosis-related proteomic profiles and specific autoantibody characteristics), elucidating the sources of clinical diversity.