By intersecting DEGs with WGCNA module genes, we identified CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes between MMD and SLE, potentially linked to immunity and inflammation regulatory activity.MPZL3were found to be valuable diagnostic markers. The gene discussed is CD68; the disease is systemic lupus erythematosus.