Ankylosing Spondylitis (AS) and Rheumatoid Arthritis (RA) are the most common rheumatic diseases with complex diagnoses. Improving the diagnosis and treatment success rates for these conditions while reducing prevalence and disability rates has become a pressing global medical challenge. Since the causes of AS and RA remain unclear, understanding their pathogenic mechanisms could bring about revolutionary changes in diagnostic and therapeutic strategies. Funded by 16 “973”, “863” projects, key National Natural Science Foundation grants, and Shanghai Science and Technology Commission initiatives, this project focused on the genetic backgrounds of these diseases. Through various research techniques, it conducted in-depth studies on susceptibility genes and immune functions in the Han Chinese population, identified the underlying pathogenic mechanisms, and contributed to the development of new treatment strategies. The main achievements include: 1. Research on pathogenic mechanisms: It was the first in China to carry out immunogenetic studies on AS and RA. In AS research, ERAP1 was confirmed as associated with the disease in Han Chinese AS patients for the first time in China; STAT3 was found to be linked to AS onset, followed by the discovery that rare IL23R variants are related to AS. The project also participated in the IGAS global multicenter study, identifying 24 susceptibility genes that advanced genetic research on AS significantly. In RA research, the team was among the first in China to conduct series of immunogenetic studies on RA. They reported for the first time that MMEL1 and CTLA4 are susceptibility genes for RA in Han Chinese, initiated the first GWAS study on RA in China, and discovered a new susceptibility gene, DPP4, for RA on an international scale. As the only Chinese participant in an international cross-ethnic RA study, they identified 101 pathogenic loci, including 42 newly detected risk sites. Combining immunological studies on Tregs and cytokines such as IL18 and IL22, these findings deepened our understanding of the pathogenic mechanisms and helped develop new treatment strategies. 2. Development of treatment strategies: Based on the association between IL23R/STAT3 and AS onset, the team was among the first internationally to demonstrate the role of TH17 cells in AS pathogenesis, contributing to the widespread use of anti-IL-17 antibodies worldwide and improving outcomes for AS patients. Independent and collaborative studies on RA identified 871 target gene drugs as potential candidates, greatly accelerating drug development. To date, the team has conducted 16 phase III clinical trials for AS and RA, helping shape treatment strategies for these diseases. Research on AS subtypes such as B27 has promoted precise diagnosis, while MMP3 combined with ultrasound monitoring effectively tracks disease progression and provides objective metrics for evaluating the effectiveness of drug therapy. This project has guided the diagnosis and treatment of tens of thousands of AS and RA patients across more than 30 institutions in China. Alone, the Changzheng Hospital conducts over 5,000 standardized diagnoses annually. A total of 120 papers have been published, including 49 in SCI journals—9 of which were authored by the corresponding or first authors in the top rheumatology journal Ann Rheum Dis (impact factor 12.35 in 2017), and 6 in Arthritis Rheumatol (impact factor 8.955 in 2017), with 5 of those also by the corresponding or first authors. Additionally, 3 papers were co-authored in Nature and Nature Genetics (the only Chinese institution involved in these collaborations). The cumulative impact factor of all published papers is 362.904, with 2,940 citations in SCI journals.