This first cross-disease analysis of the innate gene expression signature of 10 TLRs, 7 key members of the IL1/IL1R family, and interleukin 8 (CXCL8) in peripheral blood mononuclear cells (PBMC) from patients with active SLE, RA, and SSc revealed emerging diversity and abundance in RA compared to SLE and SSc. This evidence concerns the gene IL1A and systemic sclerosis.