Our phenotypic and functional studies revealed reduced BTLA expression on CD27<sup>-</sup>IgD<sup>+</sup> naïve B cells from SLE patients (p=0.0017) related to anti-dsDNA antibody titers (p=0.0394) and SIGLEC-1/CD169 expression on monocytes (p=0.0196), a type I interferon marker related to disease activity. Here, BTLA is linked to systemic lupus erythematosus.