Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis

Abstract

To the Editors: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterised by excessive accumulation of surfactant materials within alveolar spaces [1]. Patients with autoimmune PAP (aPAP) present a high level of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (GM-Ab) in the serum as well as in bronchoalveolar lavage fluid (BALF) [2]. GM-Ab neutralise the biological activity of GM-CSF in the lung [3], impairing terminal differentiation of alveolar macrophages and macrophage-mediated pulmonary surfactant clearance [4]. Based on the aetiology, clinical trials of exogenous GM-CSF supplementation have been carried out by a number of physicians with variable response rates ranging from 40 to 62% [5–9]. Previously, we reported that in three patients who received a pilot GM-CSF inhalation therapy, oxygenation was improved and the concentration of GM-Ab in BALF was reduced [7]. Bonfield et al . [8] also reported that the serum titre of GM-Ab was reduced during successful treatment of aPAP with subcutaneously injected GM-CSF. However, our recent phase II trial of GM-CSF inhalation involving 35 patients revealed that serum levels of GM-Ab remained unchanged throughout the therapy, suggesting that GM-CSF inhalation therapy did not affect the production of GM-Ab [9]. Thus, the effect of exogenous GM-CSF administration on GM-Ab levels in the serum remains controversial. This discrepancy may be due to differences in the route of administration and/or the dose of GM-CSF. Aerosolised GM-CSF reaches the lower respiratory tract and may stimulate immature alveolar macrophages directly to promote terminal differentiation and improve the local clearance of the accumulated surfactant and GM-Ab, although it does not affect the production of systemic GM-Ab. To test this hypothesis, …