Proteomic Analysis of Sputum from Adults and Children with Cystic Fibrosis and from Control Subjects

Sloane, Andrew J.; Lindner, Robyn A.; Prasad, Sindhu S.; Sebastian, Lucille; Pedersen, Susanne K.; Robinson, Michael E.; Bye, Peter; Nielson, Dennis W.; Harry, Jenny L.

doi:10.1164/rccm.200409-1215oc

Cited by 80 publications

(67 citation statements)

References 57 publications

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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%

See 1 more Smart Citation

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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Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Intense proteomics research to unveil protein markers has resulted in fi nding associations between myeloperoxidase, interleukin (IL)-8, cleaved ␣ -antitrypsin, and S100A8 (CF antigen) in sputum and the frequency of pulmonary exacerbations ( 7 ) or directly in the presence of CFTR mutations ( 8,9 ), in addition to proteomic signatures in serum or corresponding to known infl ammation markers ( 10 ) or other proteins differentially expressed in target tissues of CF before the appearance of any sign of the disease, like annexin-1 ( 11 ), cytosolic phospholipase A2 ␣ ( 11 ), cytokeratins 8 and 18 ( 12 ), and peroxiredoxin 6 ( 13,14 ). More recently, sputum proteomics has revealed that a prolineglycine-proline (PGP) peptide, an extracellular matrixderived neutrophil attractant, is a marker of infl ammatory clinical parameters at both time points.…”

mentioning

confidence: 99%

Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients

Ollero

Astarita

Guerrera

et al. 2011

Journal of Lipid Research

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Cystic fi brosis (CF) is associated with abnormal lipid metabolism. We have recently shown variations in plasma levels of several phosphatidylcholine (PC) and lysophopshatidylcholine (LPC) species related to disease severity in CF patients. Here our goal was to search for blood plasma lipid signatures characteristic of CF patients bearing the same mutation (F508del) and different phenotypes, and to study their correlation with forced expiratory volume in 1 s (FEV1) and Pseudomonas aeruginosa chronic infection, evaluated at the time of testing (t = 0) and three years later (t = 3). Samples from 44 F508del homozygotes were subjected to a lipidomic approach based on LC-ESI-MS. Twelve free fatty acids were positively correlated with FEV1 at t = 0 (n = 29). Four of them (C20:3n-9, C20:5n-3, C22:5n-3, and C22:6n-3) were also positively correlated with FEV1 three years later, along with PC(32:2) and PC(36:4) (n = 31). Oleoylethanolamide (OEA) was negatively correlated with FEV1 progression (n = 17). Chronically infected patients at t = 0 showed lower PC(32:2), PC(38:5), and C18:3n-3 and higher cholesterol, cholesterol esters, and triacylglycerols (TAG). Chronically infected patients at t = 3 showed significantly lower levels of LPC(18:0). These results suggest a potential prognostic value for some lipid signatures in, to our knowledge, the fi rst longitudinal study aimed at identifying lipid biomarkers for CF. -Ollero, M., G. Astarita, I. C. Guerrera, I. Sermet-Gaudelus, S.

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“…Interleukin (IL)-8 is the major neutrophil-attracting chemokine (11) present at high levels in airways of patients with CF (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). These high levels are likely to be responsible for abundant neutrophils in airway secretions of these patients (13,14,19,21,24,25).…”

mentioning

confidence: 99%