An Immunoproteomic Approach for Identification of Clinical Biomarkers for Monitoring Disease

Pedersen, Susanne K.; Sloane, Andrew J.; Prasad, Sindhu S.; Sebastian, Lucille; Lindner, Robyn A.; Hsu, Michael; Robinson, Michael E.; Bye, Peter T. P.; Weinberger, Ron P.; Harry, Jenny L.

doi:10.1074/mcp.m400175-mcp200

Cited by 47 publications

(41 citation statements)

References 52 publications

(50 reference statements)

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“…Increased levels of calgranulin B have also been reported in other chronic inflammatory disorders (such as cystic fibrosis and COPD) while increases in calgranulin A have been reported in acute inflammation (including ARDS) [12][13][14][15][16]. As IPF is a typical chronic disorder, the increased percentage volumes of calgranulin B found by us in this disease are in line with data in the literature [4].…”

Section: Resultssupporting

confidence: 88%

Calgranulin B (S100A9) Levels in Bronchoalveolar Lavage Fluid of Patients with Interstitial Lung Diseases

Bargagli

Olivieri

Prasse³

et al. 2008

Inflammation

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Calgranulins are small calcium-binding proteins with several immunological functions involved in inflammatory processes. Calgranulin A is reported to be mainly associated with acute inflammation while calgranulin B seems to play a role in chronic inflammatory disorders. In this study we used a proteomic approach to analyse calgranulin B expression in bronchoalveolar lavage (BAL) from a group of patients with different interstitial lung diseases. Two dimensional electrophoresis analysis of BAL was performed in 11 idiopathic pulmonary fibrosis patients, nine sarcoidosis patients, 11 with systemic sclerosis patients and five healthy controls. Significantly higher (p<0.001) calgranulin B percentage volumes were observed in BAL from IPF patients than controls and other ILD patients. This result sustains the hypothesis that calgranulin B could be involved in chronic lung diseases, probably through increased expression and enhanced activation of alveolar polymorphonuclear cells related to idiopathic pulmonary fibrosis. Quantitative analysis by an easier method applied to a larger population will be necessary to determine whether calgranulin B could be a good marker of disease severity.

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Section: Resultssupporting

confidence: 88%

Calgranulin B (S100A9) Levels in Bronchoalveolar Lavage Fluid of Patients with Interstitial Lung Diseases

Bargagli

Olivieri

Prasse³

et al. 2008

Inflammation

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“…This may lead to biomarkers of a higher mass being ignored. Other proteomics methods, such as twodimensional gel electrophoresis and immunocapture, may be better in assessing larger molecular weight proteins, and has been applied to CF (27,29).…”

Section: Discussionmentioning

confidence: 99%

“…SELDI-TOF has been used to demonstrate protein expression in BAL in CF (25,26). There is as yet a lack of published data using SELDI-TOF to profile sputum, although complementary proteomic approaches of two-dimensional electrophoresis (27), shotgun protein sequencing (28), and affinity immunoproteomics (29) have been applied to sputum in an effort to discover new biomarkers.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases

Gray

MacGregor

Noble³

et al. 2008

Am J Respir Crit Care Med

171

150

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Rationale: Markers of inflammatory activity are important for assessment and management of many respiratory diseases. Markers that are currently unrecognized may be more valuable than those presently believed to be useful. Objectives: To identify potential biomarkers of suppurative and inflammatory lung disease in induced sputum samples. Methods: Induced sputum was collected from 20 healthy control subjects, 24 patients with asthma, 24 with chronic obstructive pulmonary disease, 28 with cystic fibrosis (CF), and 19 with bronchiectasis. Twelve patients with CF had sputum sampled before and after antibiotic therapy for an infective exacerbation. The fluid phase of induced sputum was analyzed by surface-enhanced laser desorption/ ionization time-of-flight (SELDI-TOF) mass spectroscopy on three protein array surfaces. Some protein markers were selected for identification, and relevant ELISA assays sought. For 12 patients with CF, both SELDI-TOF and ELISA monitored changes in inflammatory responses during infective exacerbations. Measurements and Main Results: SELDI-TOF identified potential biomarkers that differentiated each of the disease groups from healthy control subjects: at a significance of P , 0.01, there were 105 for asthma, 113 for chronic obstructive pulmonary disease, 381 for CF, and 377 for bronchiectasis. Peaks selected for protein identification yielded calgranulin A, calgranulin B, calgranulin C, Clara cell secretory protein, lysosyme c, proline rich salivary peptide, cystatin s, and hemoglobin a. On treatment of an infective CF exacerbation, SELDI-TOF determined falls in levels of calgranulin A and calgranulin B that were mirrored by ELISA-measured falls in calprotectin (heterodimer of calgranulins A and B). Conclusions: Proteomic screening of sputum yields potential biomarkers of inflammation. The early development of a clinically relevant assay from such data is demonstrated.

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“…Expectorated sputum provides an accurate measure of infection in the CF airway (119)(120)(121). Beyond serving as a means to ascertain lower airway microbial pathogens and quantitative bacterial counts by conventional culture, sputum can be used to identify bacterial species and bacterial proteins by molecular means (122)(123)(124)(125).…”

Section: Clinical and Biologic Relevancementioning

confidence: 99%

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

Sagel

Chmiel²,

Konstan³

2007

Proceedings of the American Thoracic Society

156

162

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Pulmonary biomarkers are being used more frequently to monitor disease activity and evaluate response to treatment in individuals with cystic fibrosis (CF). This article summarizes the current state of knowledge of biomarkers of inflammation relevant to CF lung disease, and the tools to measure inflammation, with specific emphasis on sputum. Sputum is a rich, noninvasive source of biomarkers of inflammation and infection. Sputum induction, through the inhalation of hypertonic saline, has expanded the possibilities for monitoring airway inflammation and infection, especially in individuals who do not routinely expectorate sputum. We critically examine the existing data supporting the validity of sputum biomarkers in CF, with an eye toward their application as surrogate endpoints or outcome measures in CF clinical trials. Further validation studies are needed regarding the variability of inflammatory biomarker measurements, and to evaluate how these biomarkers relate to disease severity, and to longitudinal changes in lung function and other clinical endpoints. We highlight the need to incorporate sputum collection, by induction if necessary, and measurement of sputum biomarkers into routine CF clinical care. In the future, pulmonary biomarkers will likely be useful in predicting disease progression, indicating the onset and resolution of a pulmonary exacerbation, and assessing response to current therapies or candidate therapeutics.

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An Immunoproteomic Approach for Identification of Clinical Biomarkers for Monitoring Disease

Cited by 47 publications

References 52 publications

Calgranulin B (S100A9) Levels in Bronchoalveolar Lavage Fluid of Patients with Interstitial Lung Diseases

Calgranulin B (S100A9) Levels in Bronchoalveolar Lavage Fluid of Patients with Interstitial Lung Diseases

Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

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