In addition to confirming the presence of anti-KIR autoantibodies in SLE patients, our data demonstrate that these autoantibodies react with natively folded membrane-bound KIRs expressed on human cells, and that reactivity to KIR2DL2, KIR3DL2, KIR2DS2, KIR2DS4, and KIR2DL4 is also present in SLE patients. Here, KIR2DL4 is linked to systemic lupus erythematosus.