The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/9/875/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 875-880

Brief Definitive Report

Idiopathic Pulmonary Alveolar Proteinosis as an Autoimmune Disease with Neutralizing Antibody against Granulocyte/Macrophage Colony-Stimulating Factor

Takayuki Kitamuraa, Naohiko Tanakaa,b, Junichi Watanabea, Uchidaa, Shiro Kanegasakia, Yoshitsugu Yamadaa, and Koh Nakata

a The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
b Kitasato University School of Medicine, Kanagawa 228-8655, Japan
Laboratory of Culture Collection, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.81-3-5449-525481-3-5449-5391

kinkabu{at}hgc.ims.u-tokyo.ac.jp

Idiopathic pulmonary alveolar proteinosis (I-PAP) is a rare disease of unknown etiology in which the alveoli fill with lipoproteinaceous material. We report here that I-PAP is an autoimmune disease with neutralizing antibody of immunoglobulin G isotype against granulocyte/macrophage colony-stimulating factor (GM-CSF). The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases. It specifically bound GM-CSF and neutralized bioactivity of the cytokine in vitro. The antibody was also found in sera from all I-PAP patients examined but not in sera from a secondary PAP patient or normal subjects, indicating that it exists systemically in I-PAP patients. As lack of GM-CSF signaling causes PAP in congenital cases and PAP-like disease in murine models, our findings strongly suggest that neutralization of GM-CSF bioactivity by the antibody causes dysfunction of alveolar macrophages, which results in reduced surfactant clearance.

Key Words: autoantibody • granulocyte/macrophage colony-stimulating factor • pulmonary alveolar proteinosis • alveolar macrophage • surfactant protein

© 1999 The Rockefeller University Press


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