Abstract: BACKGROUND: Basement membrane genes are closely related to the occurrence and development of rheumatoid arthritis, but the role of basement membrane-related genes in the pathogenesis of rheumatoid arthritis under different traditional Chinese medicine patterns is not yet clear.
OBJECTIVE: To explore the differences in the pathogenesis of rheumatoid arthritis with five different traditional Chinese medicine syndromes based on the analysis of basement membrane-related genes and transcriptomics, and to predict potential therapeutic drugs. 
METHODS: Rheumatoid arthritis-related traditional Chinese medicine syndrome microarray data and basement membrane-related genes were collected from the GEO database. The differentially expressed genes were screened using the R-limma package, and the expression trends were analyzed using the Mfuzz package. The protein-protein interaction network was constructed using the STRING database and key genes were selected using UPset. The differentially expressed genes were subjected to gene set enrichment analysis (GSEA) and enrichment analysis using the R-clusterProfiler package. Receiver operating characteristics curves were plotted to evaluate the diagnostic value of core basement membrane-related targets for each of the five syndromes. The immune infiltration of each syndrome was calculated using the CIBERSORT algorithm. Finally, potential traditional Chinese medicines and small molecule drugs targeting core basement membrane-related genes for the treatment of different traditional Chinese medicine syndromes of rheumatoid arthritis were predicted using SymMap and COREMINE databases. 
RESULTS AND CONCLUSION: (1) 67, 47, 59, 57, and 55 basement membrane-related differentially expressed genes were screened for the five traditional Chinese medicine syndromes of rheumatoid arthritis (obstruction syndrome, cold-dampness obstruction syndrome, liver-kidney deficiency syndrome, qi-blood deficiency syndrome, and blood stasis obstructing collaterals syndrome), with 5, 7, 5, 3, and 5 key targets identified, respectively. (2) The most enriched biological processes in each syndrome were extracellular matrix adhesion, immune cell migration, collagen metabolism, and extracellular matrix receptor interaction, PI3K-Akt, focal adhesion, and Rap1 signaling pathways. (3) According to the predictions, Smilax glabra, Sargentodoxa cuneata, and Polygonatum sibiricum have the most potential as traditional Chinese medicines for the treatment of the five traditional Chinese medicine syndromes of rheumatoid arthritis by affecting basement membrane-related genes. (4) These results indicate that abnormal expression of basement membrane-related genes may affect the occurrence and development of rheumatoid arthritis through the regulation of cell adhesion, immune cell migration, and inflammatory reactions, among other pathways. These effects vary among different syndromes, with ITGA6 serving as a common diagnostic marker for the five traditional Chinese medicine syndromes of rheumatoid arthritis. Traditional Chinese medicines with heat-clearing and detoxifying properties may be potential effective drugs for the treatment of different syndromes of rheumatoid arthritis.

Key words: basement membrane-related gene, phenotype, rheumatoid arthritis, traditional Chinese medicine, transcriptomics analysis, GSEA analysis, immune infiltration, molecular docking, drug prediction, mechanism study