Platelet-derived growth factor receptor-b and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study

Introduction: Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-b (PDGFR-b) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFRand EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-b (pPDGFR-b) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation. Methods: Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity. Results: All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-b-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals. Conclusions: PDGFR-b-immunoreactivity in SScPAH is more common and intense in smalland post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-b immunoreactivity pattern is not paralleled by pPDGFR-b or PDGF-B patterns. PDGFR-band EGFRimmunoreactivity of pulmonary vessels distinguishes PAH patients from controls. * Correspondence: [email protected] Department of Pulmonary Diseases, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands Full list of author information is available at the end of the article Overbeek et al. Arthritis Research & Therapy 2011, 13:R61 http://arthritis-research.com/content/13/2/R61 © 2011 Overbeek et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.