Background: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and still incurable disease. Research of IPAH-pathogenesis is complicated by the lack of a direct access to the involved tissue, the human pulmonary vasculature. Various auto-antibodies have been described in the blood of patients with IPAH. The purpose of the present work was therefore to comparatively analyze peripheral blood B lymphocyte RNA expression characteristics in IPAH and healthy controls. Methods: Patients were diagnosed having IPAH according to WHO (mean pulmonary arterial pressure >= 25 mmHg, pulmonary capillary occlusion pressure <= 15 mmHg, absence of another explaining disease). Peripheral blood B-lymphocytes of patients and controls were immediately separated by density gradient centrifugation and magnetic beads for CD19. RNA was thereafter extracted and analyzed by the use of a high sensitivity gene chip (Affymetrix HG-U133-Plus2) able to analyze 47000 transcripts and variants of human genes. The array data were analyzed by two different softwares, and up- and down-regulations were defined as at least 1.3 fold with standard deviations smaller than fold-changes. Results: Highly purified B-cells of 5 patients with IPAH (mean pulmonary artery pressure 51 +/- 13 mmHg) and 5 controls were analyzed. Using the two different analyzing methods we found 225 respectively 128 transcripts which were up- regulated (1.3-30.7 fold) in IPAH compared with healthy controls. Combining both methods, there were 33 overlapping up-regulated transcripts and no down-regulated B-cell transcripts. Conclusion: Patients with IPAH have a distinct RNA expression profile of their peripheral blood B-lymphocytes compared to healthy controls with some clearly up-regulated genes. Our finding suggests that in IPAH patients B cells are activated.
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