Recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation in a patient with a nonsense mutation in CSF2RB.
Hereditary pulmonary alveolar proteinosis (PAP) caused by mutations in CSF2RA or CSF2RB, which encode GM-CSF receptor α and β respectively, is a rare disease. Although some experimental therapeutic strategies have been proposed, no clinical evidence has yet been reported. We herein describe the clinical course and recurrence of hereditary PAP after lung transplantation. A 36-year-old woman developed PAP of unknown etiology. She underwent bilateral lung transplantation from living donors at the age of 42 years because of severe respiratory failure complicated by pulmonary fibrosis. However, PAP recurred after 9 months, and we found that donor-origin alveolar macrophages had been almost completely replaced with recipient-origin macrophages. We performed a genetic analysis and identified a point deletion in the CSF2RB gene that caused a GM-CSF receptor-mediated signaling defect. PAP progressed with fibrosis in both transplanted lungs, and the patient died of respiratory failure 5 years after the lung transplantation. Distinct from recent reports on pulmonary macrophage transplantation in mice, this case suggests that human alveolar macrophages might not maintain their population only by self-renewal but may depend on a supply of precursor cells from the circulation. Bone marrow transplantation should be considered for treatment of severe PAP with GM-CSF receptor gene deficiency.
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan.
Masahiro
M
Takaki
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan.
Takeshi
T
Tanaka
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yoshihiro
Y
Komohara
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan.
Yoshiko
Y
Tsuchihashi
Department of Pathology, Saga-ken Medical Centre Koseikan, Saga, Japan.
Daisuke
D
Mori
Department of Pathology, Nagasaki University, Nagasaki, Japan.
Kentaro
K
Hayashi
Department of Pathology, Nagasaki University, Nagasaki, Japan.
Junya
J
Fukuoka
Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Naoya
N
Yamasaki
Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Takeshi
T
Nagayasu
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan.
Koya
K
Ariyoshi
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki, Japan.
Konosuke
K
Morimoto
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
Koh
K
Nakata
Hereditary pulmonary alveolar proteinosis; Lung transplantation; Recurrence; aPAP, autoimmune pulmonary alveolar proteinosis; hPAP, hereditary pulmonary alveolar proteinosis