Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma.
BACKGROUND
Neutrophilic airway inflammation is frequently observed in severe uncontrolled asthma (UA) and controlled asthma (CA). However, there is no sputum biomarker to differentiate the 2 conditions.


OBJECTIVE
To identify biomarkers of severe uncontrolled asthma with neutrophilic airway inflammation.


METHODS
Sputum with a neutrophil content larger than 70% was pooled from 5 patients with severe UA and from 10 patients with CA. Two-dimensional electrophoresis was adopted for differential display proteomics, and candidate proteins were identified using matrix-assisted laser adsorption/ionization-time of flight mass spectrometric analysis. S100 calcium binding protein A9 (S100A9) was identified by western blot and its level was measured in sputum from asthmatics with varying disease severity, patients with chronic obstructive lung disease, and normal controls using enzyme-linked immunosorbent assay.


RESULTS
Fourteen protein spots exhibited differences in relative intensity between patients with severe UA and those with CA. Matrix-assisted laser adsorption/ionization-time of flight/time of flight of these spots showed an increase in human neutrophil peptide-2, S100A9, β-amylase, neutrophil gelatinase-associated lipocalin, 4-aminobutyrate transaminase, and cystatin SA in patients with UA compared with patients with CA. There was a decrease in the plunc precursor, complement C3 component, immunoglobulin heavy-chain variable region, glial fibrillary acidic protein isoform-1, IgM κIIIb SON, MLL-AF4 der(11) fusion protein, cytokeratin-8, and recombinant IgG4 heavy chain. S100A9 was detected at a higher level in western blots of neutrophilic sputum from patients with severe UA vs CA. S100A9 levels were significantly increased, as measured by enzyme-linked immunosorbent assay, in neutrophilic UA compared with CA, eosinophilic UA and CA, and chronic obstructive lung disease.


CONCLUSIONS
S100A9 in sputum may be a biomarker of neutrophilic inflammation in severe UA.
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Tae-Hyeong
TH
Lee
An-Soo
AS
Jang
Jong-Sook
JS
Park
Tae-Hoon
TH
Kim
Young Suk
YS
Choi
Hye-Rim
HR
Shin
Sung-Woo
SW
Park
Soo-Taek
ST
Uh
Jae-Sung
JS
Choi
Young Hoon
YH
Kim
Yongbae
Y
Kim
Sungryul
S
Kim
Il Yup
IY
Chung
Sung Hwan
SH
Jeong
Choon-Sik
CS
Park
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000276:immunology*; D015415:Biomarkers; D040502:Calgranulin B / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D020543:Proteome / Q000032:analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology; D013183:Sputum / Q000276:immunology*; D055815:Young Adult
D015415:Biomarkers; D040502:Calgranulin B; D020543:Proteome