RT Journal Article
SR Electronic
T1 Granulysin in pulmonary veno-occlusive disease
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P481
VO 42
IS Suppl 57
A1 Frédéric Perros
A1 Sylvia Cohen-Kaminsky
A1 Natalia Gambaryan
A1 Barbara Girerd
A1 Nicolas Raymond
A1 Isabelle Klingelschmitt
A1 Alice Huertas
A1 Olaf Mercier
A1 Elie Fadel
A1 Gerald Simonneau
A1 Marc Humbert
A1 Peter Dorfmüller
A1 David Montani
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P481.abstract
AB Background: Pulmonary Veno-Occlusive Disease (PVOD) shares many similarities with precapillary Pulmonary Arterial Hypertension (PAH), from risk factors to clinical or hemodynamic presentation. The need to establish a correct diagnosis of PVOD is justified by the worse prognosis of these patients and by their risk of developing severe pulmonary edema with specific PAH therapy.Aims and objectives: To show that the cytolytic subpopulation of inflammatory cells is differently regulated in PAH and PVOD patients and to identify a biological tool to distinguish these two entities.Methods: The functional status of the cytolytic compartment was studied through epigenetic analysis of the Granulysin (GNLY), a powerful effector for these subpopulations in explanted lungs and in PBMC. Flow cytometry allowed analysis of circulating cytolytic cells and GNLY contents. A GNLY-specific ELISA allowed measurement of GNLY serum concentrations.Results: A decrease in GNLY demethylation in the DNA extracted from PBMC and lungs was found in PVOD but not in PAH. This was associated with a decrease in populations and subpopulations of cytotoxic T-(CTL), and Natural Killer T-(NKT) cells, and an increase of Natural Killer-(NK) populations. Despite the reduced GNLY-containing cells in PVOD, GNLY serum levels were higher, suggesting these cells were wasting their content. Furthermore, the increase of GNLY concentration in the serum of PVOD was higher than in PAH patients.Conclusions: PVOD is characterized by alterations of circulating cytotoxic cell-subpopulations and by epigenetic dysregulation within the GNLY gene. Our findings may be helpful to develop needed biological tools in order to screen for suspected PVOD in patients with pulmonary hypertension.