Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile.
BMC Pulm Med
; 17(1): 40, 2017 02 17.
Article
en En
| MEDLINE
| ID: mdl-28212655
ABSTRACT
BACKGROUND:
Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. CASE PRESENTATION The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage. She tested negative for GM-CSF autoantibodies, with no underlying disease. Her serum GM-CSF level was elevated (91.3 pg/mL), indicating GM-CSF signaling impairment and genetic defects in the GM-CSF receptor. GM-CSF-stimulated phosphorylation in signal transducer and activator of transcription 5 (STAT5) was not observed, and GM-CSF-Rα expression was defective in her blood cells. Genetic screening revealed a homozygous, single-base C > T mutation at nt 508-a nonsense mutation that yields a stop codon (Q170X)-in exon 7 of CSF2RA. High-resolution analysis of single nucleotide polymorphism array confirmed a 22.8-Mb loss of heterozygosity region in Xp22.33p22.11, encompassing the CSF2RA gene. She was successfully treated with whole lung lavage (WLL), which reduced the serum levels of interleukin (IL)-2, IL-5, and IL-17, although IL-3 and M-CSF levels remained high.CONCLUSIONS:
This is the first known report of elderly-onset hPAP associated with a CSF2RA mutation, which caused defective GM-CSF-Rα expression and impaired signaling. The analyses of serum cytokine levels during WLL suggested that GM-CSF signaling might be compensated by other signaling pathways, leading to elderly-onset PAP.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteinosis Alveolar Pulmonar
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Factor Estimulante de Colonias de Granulocitos y Macrófagos
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Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos
Límite:
Aged
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Female
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Humans
Idioma:
En
Revista:
BMC Pulm Med
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón