In non-target cohorts, the SLE model showed moderate discrimination for RA (AUC 0.73) but limited discrimination for ICU sepsis (AUC 0.64) and none for non-infectious critical illness (AUC 0.50), while the IPF model showed minimal discrimination for RA (AUC 0.51) but high discrimination for ICU groups (AUC 0.99 and 0.96).<h4>Conclusions</h4>GRN and KLRB1 anchor a shared peripheral-blood transcriptomic signature linking SLE and IPF, enabling parsimonious diagnostic models with multi-cohort validation and clinical experimental support. Here, KLRB1 is linked to systemic lupus erythematosus.