Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan

Ishii, Haruyuki; Tazawa, Ryushi; Kaneko, Chinatsu; Saraya, Takeshi; Inoue, Yoshikazu; Hamano, Emi; Kogure, Yoshihito; Tomii, Keisuke; Tomita, Masaki; Takada, Toshinori; Hojo, Masaaki; Nishida, Aya; Ichiwata, Toshio; Trapnell, Bruce C.; Goto, Hajime; Nakata, Koh

doi:10.1183/09031936.00092910

Cited by 84 publications

(127 citation statements)

References 11 publications

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“…Of note, its association with myelodysplastic syndrome (MDS) has also been well documented. [19][20][21][22][23] The findings of the present study demonstrate an unexpected link between T-bet overexpression in T lymphocytes and PAP development caused by functional and maturation impairment of mononuclear phagocytes in the lung, and provide new insight into the molecular pathogenesis of secondary PAP accompanied by hematologic disorders.…”

Section: Naïve Cd4mentioning

confidence: 93%

T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

Iriguchi

Kikuchi

Kaneko

et al. 2015

Blood

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Key Points• Mice overexpressing T-bet in T cells show aberrant hematopoiesis of myeloid cells and functional conversion of regional macrophages.• The mice developed a severe PAP-like disease with a hematopoietic disorder resembling the human disease.Although overexpression of T-bet, a master transcription factor in type-1 helper T lymphocytes, has been reported in several hematologic and immune diseases, its role in their pathogenesis is not fully understood. In the present study, we used transgenic model mice (T-bet tg/wt and T-bet tg/tg ) to investigate the effects of T-bet overexpression selectively in T lymphocytes on the development of hematologic and immune diseases. The results showed that T-bet overexpression in T cells spontaneously induced maturation arrest in the mononuclear phagocyte lineage, as well as spontaneous dermatitis and pulmonary alveolar proteinosis (PAP)-like disease in T-bet tg/wt and T-bet tg/tg mice, respectively. T-bet tg/tg alveoli with the PAP phenotype showed remarkable reorganization of alveolar mononuclear phagocyte subpopulations and impaired function, in addition to augmented T-cell infiltration. In addition, PAP development in T-bet tg/tg mice was found to be associated with increased migration of myeloid cells from the bone marrow into the peripheral blood. These findings reveal an unexpected link between T-bet overexpression in T lymphocytes and the development of PAP caused by reorganization of mononuclear phagocytes in the lung, and provide new insight into the molecular pathogenesis of secondary PAP accompanied by hematologic disorders. (Blood. 2015;125(2):370-382)

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Section: Naïve Cd4mentioning

confidence: 93%

T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

Iriguchi

Kikuchi

Kaneko

et al. 2015

Blood

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“…The association of PAP and haematological disorders is well established, mostly myelodysplastic syndromes and acute myeloid leukaemia [52]. PAP could explain up to 10% of pulmonary manifestations during these diseases [54].…”

Section: Cancermentioning

confidence: 99%

“…A few cases of connective tissue diseases have been reported: dermatomyositis [49], rheumatoid arthritis [50] and Behcet's disease [51,52]. One study suggested that pulmonary pneumocystosis secondary to HIV infection could induce PAP [53].…”

Section: Secondary Papmentioning

confidence: 99%

Pulmonary alveolar proteinosis

Borie¹,

Danel²,

Mp³

et al. 2011

Eur Respir Rev

244

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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“…(b) In the case of secondary PAP, GM-CSF neutralizing autoantibodies are not involved. Secondary PAP has either been preceded by malignant hematological diseases (according to Ishii et al 2011 in more than 75%) or high exposure to poorly soluble particles from mineral or metallic/metalloid substances. This means that the latter represents only a very small percentage of all human PAP cases described (Briens et al 2002;Inoue et al 2008;Ishii et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Secondary PAP has either been preceded by malignant hematological diseases (according to Ishii et al 2011 in more than 75%) or high exposure to poorly soluble particles from mineral or metallic/metalloid substances. This means that the latter represents only a very small percentage of all human PAP cases described (Briens et al 2002;Inoue et al 2008;Ishii et al 2011). (c) In rare cases, inherited genetic defects are present as a result of recessive mutations in the receptors of the GM-CSF effects (Suzuki et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

Bomhard¹

2017

Toxicol Pathol

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This review analyzes the published data on cases of pulmonary alveolar proteinosis (PAP) in workers inhaling crystalline aluminum, indium, silicon, and titanium particles and possible sequelae, that is, inflammation and fibrosis, and compares these findings with those from animal experiments. In inhalation studies in rodents using crystalline indium and gallium compounds, pronounced PAP followed by inflammation and fibrosis down to very low concentration ranges have been reported. Crystalline aluminum, silicon, and titanium compounds also induced comparable pulmonary changes in animals, though at higher exposure levels. Laboratory animal species appear to react to the induction of PAP with varying degrees of sensitivity. The sensitivity of humans to environmental causes of PAP seems to be relatively low. Up to now, no cases of PAP, or other pulmonary diseases in humans, have been described for gallium compounds. However, a hazard potential can be assumed based on the results of animal studies. Specific particle properties, responsible for the induction of PAP and its sequelae, have not been identified. This review provides indications that, both in animal studies and in humans, PAP is not often recognized due to the absence of properly directed investigation or is concealed behind other forms of lung pathology.

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Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan

Cited by 84 publications

References 11 publications

T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

Pulmonary alveolar proteinosis

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

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