[HTML][HTML] A chitinase-like protein in the lung and circulation of patients with severe asthma

GL Chupp, CG Lee, N Jarjour, YM Shim… - … England Journal of …, 2007 - Mass Medical Soc
GL Chupp, CG Lee, N Jarjour, YM Shim, CT Holm, S He, JD Dziura, J Reed, AJ Coyle…
New England Journal of Medicine, 2007Mass Medical Soc
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 …
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.
The New England Journal Of Medicine