Serological Diagnosis of Idiopathic Pulmonary Alveolar Proteinosis

Kitamura, Takayuki; Uchida, Kanji; Tanaka, Naomichi; Tsuchiya, Tomoko; Watanabe, Junichi; Yamada, Yosuke; Hanaoka, Kazuo; Seymour, John F.; Schoch, Otto D.; Doyle, Ian; Inoue, Yoshikazu; Sakatani, Mitsunori; Kudoh, Shoji; Azuma, Arata; Nukiwa, Toshihiro; Tomita, Tomoyuki; Katagiri, Makoto; Fujita, Akira; Kurashima, Atsuyuki; Kanegasaki, Shiro; Nakata, Koh

doi:10.1164/ajrccm.162.2.9910032

Cited by 193 publications

(139 citation statements)

References 15 publications

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“…Measurement of serum anti-GM-CSF antibodies is used for the diagnosis of autoimmune PAP (Kitamura et al 2000;Uchida et al 2014). Serum KL-6 could be the useful Gallium-67 ( 67 Ga) scintigraphy on first admission detected abnormal 67 Ga accumulation in bilateral hilar and mediastinal lymph nodes, liver, and bilateral upper arms (arrow head).…”

Section: Discussionmentioning

confidence: 99%

“…1). We thus diagnosed her as also having autoimmune PAP according to the following diagnostic criteria: cytological analysis of BALF or pulmonary histopathological findings, chest CT findings, and elevation of serum anti-GM-CSF antibodies levels (≥ 1.0 µg/mL) (Kitamura et al 2000;Uchida et al 2014). Six months after the diagnosis of autoimmune PAP, we administered the wedge resection of the left lower lobe for the enlargement of a small nodule with the diameter of 17 mm in the left S…”

Section: Case Reportmentioning

confidence: 99%

“…Autoimmune PAP is the most common form of PAP, which consists of approximately 90% of PAP (Trapnell et al 2003). The anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies are specifically detected in serum and bronchoalveolar lavage (BAL) from patients with autoimmune PAP (Kitamura et al 1999(Kitamura et al , 2000. The autoantibodies neutralize the biological activity of GM-CSF and impair the clearance of pulmonary surfactant by macrophages, leading to the accumulation of surfactant proteins and cellular debris in the alveolar space and disruption of gas exchange (Kitamura et al 1999;Uchida et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis

Yamasue

Nureki

Usagawa

et al. 2017

Tohoku J. Exp. Med.

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Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-schiff stainpositive lipoproteinaceous materials in the alveolar space due to impaired surfactant clearance by alveolar macrophage. Autoimmune PAP is the most common form of PAP, but rarely accompanies collagen disease or sarcoidosis. We report here a rare case of autoimmune PAP preceded by systemic sclerosis and sarcoidosis. A 64-year-old woman was admitted to our hospital for blurred vision, muscle weakness of extremities, Raynaud's phenomenon, and exertional dyspnea. We diagnosed her as having systemic sclerosis complicated with sarcoidosis. Chest computed tomography (CT) and transbronchial lung biopsy showed the findings of pulmonary fibrosis without PAP. We treated her with corticosteroid and intravenous cyclophosphamide therapy, followed by tacrolimus therapy. Thereafter, her symptoms improved except for exertional dyspnea, and she began to complain of productive cough thirteen months after corticosteroid and immunosuppressant therapy. On the second admission, a chest CT scan detected the emergence of crazy-paving pattern in bilateral upper lobes. Bronchoalveolar lavage (BAL) fluid with milky appearance and a lung biopsy specimen revealed acellular periodic acid-schiff stain-positive bodies. The serum titer of anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies was elevated on first admission and remained high on second admission. We thus diagnosed her as having autoimmune PAP. Reducing the dose of immunosuppressive agents and repeating the segmental BAL resulted in the improvement of her symptoms and radiological findings. Immunosuppressant therapy may trigger the onset of autoimmune PAP in a subset of patients with systemic sclerosis and/or sarcoidosis.

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Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis

Yamasue

Nureki

Usagawa

et al. 2017

Tohoku J. Exp. Med.

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“…It has diagnostic sensitivity and specificity of 100% and 98%, respectively, so it is the test of choice for autoimmune pulmonary alveolar proteinosis. 128 …”

Section: Tissue Biopsymentioning

confidence: 99%

Pulmonary Alveolar Proteinosis

Khan

Agarwal

2011

Respir Care

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“…Adding to the etiopathogenesis of this lung disease, the presence of blocking anti-GM-CSF antibodies was demonstrated in the broncho-alveolar lavage fluids and sera from patients with idiopathic (noncongenital) PA P. These antibodies seem to be absent in the established secondary forms of the disease, in subjects with another type of lung disease and in most healthy controls (52,53).Thus, this observation suggests a high diagnositic value for the presence of anti-GM-CSF antibodies in patients with idiopathic, but not secondary or congenital, PA P. Yet, it remains to be determined whether the presence of anti-GM-CSF antibodies is secondary or primary in these pat i e n t s .…”

Section: Alveolar Proteinosismentioning

confidence: 99%

Clinical Biological and Genetic Heterogeneity of the Inborn Errors of Pulmonary Surfactant Metabolism

Tredano¹,

Blic²,

Griese³

et al. 2001

Clinical Chemistry and Laboratory Medicine

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Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active propert i e s ) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surfactant proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the s u rfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the S F T P B gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colonystimulating factor (GM-CSF) (C s f g m) or the ␤ subunit of its receptor (I l 3 r b 1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar lavages, GM-CSF replacement, bone marrow grafting or lung transplantation.

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Serological Diagnosis of Idiopathic Pulmonary Alveolar Proteinosis

Cited by 193 publications

References 15 publications

Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis

Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis

Pulmonary Alveolar Proteinosis

Clinical Biological and Genetic Heterogeneity of the Inborn Errors of Pulmonary Surfactant Metabolism

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