Emerging diversity and abundance of the innate signature in RA patients were detected: RA was characterized by the upregulation of TLR3, TLR5, IL1RAP/IL1R3, IL18R1, and SIGIRR/IL1R8 when compared to SSc (Pcorr < 0.02) and of TLR2, TLR5, and SIGIRR/IL1R8 when compared to SLE (Pcorr < 0.02). Here, SIGIRR is linked to systemic lupus erythematosus.