Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis

Bonella, Francesco; Ohshimo, Shinichiro; Cai, Ming; Griese, Matthias; Guzman, Josune; Costabel, Ulrich

doi:10.1186/1750-1172-8-53

Cited by 45 publications

(39 citation statements)

References 33 publications

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“…marker for not only the disease activity of pulmonary fibrosis (Kohno et al 1989), but also for the monitoring of autoimmune PAP (Inoue et al 2006;Lin et al 2008;Bonella et al 2013). In our case, at the time of the diagnosis of sarcoidosis and systemic sclerosis, the chest CT scan, BAL, and trans-bronchial lung biopsy could not show the existence of autoimmune PAP; however, serum KL-6 and anti-GM-CSF antibodies levels were already highly elevated.…”

Section: Discussionmentioning

confidence: 99%

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%

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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“…In this study, similar methods as described in previous studies (4,5) were used to compare the serum KL-6 levels of PAP patients of different ethnicities. We found that the mean serum KL-6 level of Chinese PAP patients was significantly higher than that of German PAP patients but close to that of Japanese PAP patients, when there was no significant difference in disease severity.…”

Section: Discussionmentioning

confidence: 99%

“…Bonella et al (5) have reported the levels of KL-6 in German Caucasian PAP patients. We found that the serum KL-6 level was significantly higher in Chinese patients with PAP than in German patients (Chinese group: 8,248±9,544 U/mL, German group: 2,049±1,893 U/mL, P<0.001; Table 4), despite the fact that similar methods were used to estimate the KL-6 levels; no significant differences in disease severity were observed [PaO 2 , P(A-a)O 2 , FVC, DLCO, and LDH levels].…”

Section: Correlation Between Initial Serum Kl-6 Level and The Need Fomentioning

confidence: 99%

“…However, the results of these two studies (4,5) revealed that there was a significant difference in the mean serum KL-6 level between Japanese and Caucasian PAP patients, despite the fact that the same method and reagents were used for the measurements.…”

Section: Introductionmentioning

confidence: 96%

“…To examine this hypothesis, we measured serum KL-6 levels in Chinese patients with PAP, using similar methods as described in the above two studies (4,5), and compared the results with the serum levels reported in patients of other ethnicities. We also explored the clinical implications of serum KL-6 level in Chinese PAP patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Serum KL-6 in pulmonary alveolar proteinosis: China compared historically with Germany and Japan

Guo¹,

Zhou²,

Chen³

et al. 2017

J. Thorac. Dis.

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Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis

Chen

Deutsch

Schulert

et al. 2022

Arthritis & Rheumatology

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Objective Recent observations in systemic juvenile idiopathic arthritis (JIA) suggest an increasing incidence of high‐mortality interstitial lung disease often characterized by a variant of pulmonary alveolar proteinosis (PAP). Co‐occurrence of macrophage activation syndrome (MAS) and PAP in systemic JIA suggests a shared pathology, but patients with lung disease associated with systemic JIA (designated SJIA‐LD) also commonly experience features of drug reaction such as atypical rashes and eosinophilia. This study was undertaken to investigate immunopathology and identify biomarkers in systemic JIA, MAS, and SJIA‐LD. Methods We used SOMAscan to measure ~1,300 analytes in sera from healthy controls and patients with systemic JIA, MAS, SJIA‐LD, or other related diseases. We verified selected findings by enzyme‐linked immunosorbent assay and lung immunostaining. Because the proteome of a sample may reflect multiple states (systemic JIA, MAS, or SJIA‐LD), we used regression modeling to identify subsets of altered proteins associated with each state. We tested key findings in a validation cohort. Results Proteome alterations in active systemic JIA and MAS overlapped substantially, including known systemic JIA biomarkers such as serum amyloid A and S100A9, and novel elevations in the levels of heat‐shock proteins and glycolytic enzymes. Interleukin‐18 levels were elevated in all systemic JIA groups, particularly MAS and SJIA‐LD. We also identified an MAS‐independent SJIA‐LD signature notable for elevated levels of intercellular adhesion molecule 5 (ICAM‐5), matrix metalloproteinase 7 (MMP‐7), and allergic/eosinophilic chemokines, which have been previously associated with lung damage. Immunohistochemistry localized ICAM‐5 and MMP‐7 in the lungs of patients with SJIA‐LD. The ability of ICAM‐5 to distinguish SJIA‐LD from systemic JIA/MAS was independently validated. Conclusion Serum proteins support a systemic JIA–to‐MAS continuum; help distinguish systemic JIA, systemic JIA/MAS, and SJIA‐LD; and suggest etiologic hypotheses. Select biomarkers, such as ICAM‐5, could aid in early detection and management of SJIA‐LD.

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Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis

Cited by 45 publications

References 33 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

Serum KL-6 in pulmonary alveolar proteinosis: China compared historically with Germany and Japan

Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis

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