Here, we describe for the first time the prevalence of S1PR-aAb including the first identification of S1PR2- and S1PR3-aAb in a large cohort of patients and healthy individuals, and report their potential use as both biomarkers and potential therapeutic targets in SSc, PAH, and/or lung fibrosis. The gene discussed is S1PR2; the disease is pulmonary arterial hypertension.