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. Here, DEFA3 is linked to multiminicore myopathy.