Elevated α-defensin levels in plasma of patients with pulmonary sarcoidosis

Background and objectives: Pathogens such as mycobacteria and proprionibacterium have been implicated in the pathogenesis of sarcoidosis. (x-Defensins (DF) are naturally occurring antimicrobial peptides. The aim of the present study was to assess whether DF are increased in the airway and/ or systemic circulation in patients with pulmonary sarcoidosis and whether DF levels are related to sarcoidosis disease activity. Methods: DF levels in plasma and BAL fluid (BALF) were measured in 30 patients with pulmonary sarcoidosis and in 10 controls. Plasma and BALF DF levels were compared according to disease activity. Molecular forms were analysed using reverse-phase (RP) HPLC to confirm plasma and BALF DF kinetics in pulmonary sarcoidosis. Results: DF concentrations in plasma and BALF were higher in patients with pulmonary sarcoidosis than in the controls. Plasma DF levels correlated with lysozyme but not with angiotensinconverting enzyme. These levels were high in patients in whom more organs were involved, whereas BALF DF levels were higher in patients at stage II or III than with those at sarcoidosis I. RP-HPLC showed high plasma levels of pro-defensins, DF precursors from the bone marrow, in sarcoidosis, although DF in peripheral neutrophils and BALF were the mature type. Conclusions: High plasma DF concentrations resulted from bone marrow stimulation and seemed to be associated with disease activity, whereas BALF DF were released from accumulated neutrophils in the lungs and may contribute to parenchymal involvement in sarcoidosis.