Serum concentrations of midkine (a growth factor) and follistatin-related protein 3 (FSTL3) could discriminate between patients with limited cutaneous systemic sclerosis (lcSSc) who did and did not have pulmonary arterial hypertension (PAH) in a discovery cohort of 29 patients. An increased serum concentration of both midkine and FSTL3 (as measured by enzyme-linked immunosorbent assay) was validated as a biomarker for PAH in two independent cohorts of patients with lcSSc (n = 35, n = 29), in which it had a sensitivity of 76% and 91%, respectively, and a specificity of 76% and 81%, respectively.