This paper found that: (1) CXCL4 is a new autoantigen for both B-cells and T-cells in SSc; (2) antibodies to CXCL4 correlate with the IFN-I signature; and (3) anti-CXCL4 antibodies implement IFN-α induced by CXCL4–DNA complexes in pDCs via TLR9. This evidence concerns the gene TLR9 and systemic sclerosis.