Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB

Tanaka, Takeshi; Motoi, Natsuki; Tsuchihashi, Yoshiko; Tazawa, Ryushi; Kaneko, Chinatsu; Nei, Takahito; Yamamoto, Toshiyuki; Hayashi, Tomayoshi; Tagawa, Tetsuzo; Nagayasu, Takeshi; Kuribayashi, Futoshi; Ariyoshi, Koya; Nakata, Koh; Morimoto, Konosuke

doi:10.1136/jmg.2010.082586

Cited by 95 publications

(75 citation statements)

References 19 publications

(23 reference statements)

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“…Mutation of CSF2RB was suggested in three patients presenting neonatal PAP and was recently confirmed in a 36-yr-old female and a 9-yr-old girl [8,82,83]. Both showed disease close to auto-immune PAP without detectable anti-GM-CSF antibodies but with high concentration of GM-CSF [8].…”

Section: Genetic Defects In the Gm-csf Receptormentioning

confidence: 99%

“…The mutations of CSF2RA and AFFILIATIONS *Service de Pneumologie A, Centre de Compétences des Maladies Pulmonaires Rares, CSF2RB, the coding genes of the a and b subunits, prevent GM-CSF signalling and induce PAP with intra-alveolar surfactant accumulation without interstitial infiltration. In these patients, alveolar and serum concentrations of GM-CSF are elevated and anti-GM-CSF antibodies are absent [7,8]. In PAP secondary to haematological disorders, alveolar macrophages are thought to be quantitatively or functionally unable to clear the surfactant.…”

Section: Pathophysiologymentioning

confidence: 99%

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Pulmonary alveolar proteinosis

Borie¹,

Danel²,

Mp³

et al. 2011

European Respiratory Review

240

258

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Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic ''crazy paving'' pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

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Section: Genetic Defects In the Gm-csf Receptormentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Pulmonary alveolar proteinosis

Borie¹,

Danel²,

Mp³

et al. 2011

European Respiratory Review

240

258

View full text Add to dashboard Cite

show abstract

“…This recommendation is based upon six case reports of patients with chILD syndrome who had lung pathology findings similar to those observed in adults with alveolar proteinosis due to autoimmune disease. The patients had circulating neutralizing antibodies to GM-CSF, mutations in the genes encoding the a or b subunits of GM-CSF receptor (CSF2RA or CSF2RB) (91,92,(178)(179)(180)(181), and elevated circulating GM-CSF levels (180). The recommendation reflects our judgment that the benefits of identifying a mutation in CSF2RA or CSF2RB plus elevated circulating GM-CSF levels testing (i.e., understanding more about the disease, the potential for avoiding lung biopsy, or the possibility of obtaining information that will be of importance to the family) justify the cost of genetic testing (Table E1).…”

Section: Age-specific Considerations: Infants With Slowly Progressivementioning

confidence: 99%

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

Kurland¹,

Deterding²,

Hagood³

et al. 2013

Am J Respir Crit Care Med

388

499

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“…19,20 Subsequently PAP has been shown to be strongly associated with anti-GM-CSF autoantibodies, 21 or with mutations in either of the GM-CSF receptor subunits. [22][23][24][25] Additionally, transfer of auto-antibodies from patients with anti-GM-CSF-associated PAP to non-human primates led to the formation of foamy macrophages. 26 These results indicate that GM-CSF plays an important role in the terminal differentiation of alveolar macrophages in mice and humans.…”

Section: Introductionmentioning

confidence: 99%