A chitinase-like protein in the lung and circulation of patients with severe asthma.
BACKGROUND
The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3-like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated.


METHODS
We quantified serum YKL-40 levels in three cohorts of patients with asthma--one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin--as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated.


RESULTS
Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels.


CONCLUSIONS
YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.
Chupp
Geoffrey L
GL
Yale University School of Medicine, New Haven, CT, USA. geoffrey.chupp@yale.edu
Lee
Chun Geun
CG
Jarjour
Nizar
N
Shim
Yun Michael
YM
Holm
Carole T
CT
He
Susan
S
Dziura
James D
JD
Reed
Jennifer
J
Coyle
Anthony J
AJ
Kiener
Peter
P
Cullen
Mark
M
Grandsaigne
Martine
M
Dombret
Marie-Christine
MC
Aubier
Michel
M
Pretolani
Marina
M
Elias
Jack A
JA
D054392:Adipokines; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood* / Q000145:classification / Q000473:pathology; D001324:Autoantigens / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D003430:Cross-Sectional Studies; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D008168:Lung / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D054392:Adipokines; D001324:Autoantigens; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins