耶魯大學(xué)醫(yī)學(xué)院的研究人員在11月15日的《新英格蘭醫(yī)學(xué)雜志》上公布說,，他們的研究證實(shí)通過對(duì)血液樣品中一種蛋白質(zhì)的測(cè)量，能夠確定處患有最嚴(yán)重形式的哮喘的患者,。也就是說，這種蛋白質(zhì)可能成為一種新的哮喘生物標(biāo)志物,。
這種叫做YKL-40的新生物標(biāo)志物的確定,，使研究人員向著治療無數(shù)一直很難治愈的嚴(yán)重哮喘靠近了一步。這項(xiàng)研究是耶魯大學(xué)與來自威斯康辛大學(xué)和法國巴黎大學(xué)以及MedImmune公司的研究人員合作完成,。
哮喘是一種慢性肺病,，在美國影響著3000萬人的健康,，其中有900萬是兒童。這種病的特征是氣管慢性炎癥和結(jié)構(gòu)性變化,，其癥狀在一些患者中較嚴(yán)重而在其他患者中則比較溫和,。
研究人員對(duì)三個(gè)哮喘組和對(duì)照組中253名成年患者的YKL-40（類幾丁質(zhì)酶蛋白）蛋白的血清水平。他們發(fā)現(xiàn),，與正常人相比,，哮喘患者血清中的YKL-40水平明顯增加。另外,，血液中YKL-40的水平與哮喘的嚴(yán)重程度,、肺功能和患者氣管壁的厚度有關(guān)。
這項(xiàng)研究的結(jié)果證實(shí),，YKL-40在嚴(yán)重哮喘患者中明顯增多,。因此，通過進(jìn)行血液化驗(yàn)來分析哮喘的方法將可能用于哮喘研究和檢測(cè)治療哮喘方法的效果,。
研究人員表示,，今后研究需要確定YKL-40血液化驗(yàn)在哮喘治療中的作用。而這項(xiàng)新研究則首次確定處能夠通過簡單的血液化驗(yàn)就能夠獲得的一個(gè)參數(shù),。
耶魯大學(xué)醫(yī)學(xué)院 (Yale University School of Medicine)肺病和危重病急救醫(yī)學(xué)部以及內(nèi)科醫(yī)藥部門主調(diào)查員 Geoffrey Chupp 表示,，他們希望這些結(jié)果會(huì)促進(jìn)未來的研究就YKL-40 水平和疾病活動(dòng)性如何相關(guān)以及該蛋白成為哮喘控制和研究的生物目標(biāo)的潛在可能獲取更多知識(shí)。
盡管現(xiàn)階段還需要更多數(shù)據(jù)支持這些成果,，但是他們相信這些結(jié)果能夠說明YKL-40的生物特征應(yīng)該整合到對(duì)哮喘病理學(xué)的理解中去,。
原始出處:
A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma
Geoffrey L. Chupp, M.D., Chun Geun Lee, M.D., Ph.D., Nizar Jarjour, M.D., Yun Michael Shim, M.D., Carole T. Holm, R.N., Susan He, M.D., James D. Dziura, Ph.D., M.P.H., Jennifer Reed, Ph.D., Anthony J. Coyle, Ph.D., Peter Kiener, Ph.D., Mark Cullen, M.D., Martine Grandsaigne, Marie-Christine Dombret, M.D., Michel Aubier, M.D., Marina Pretolani, Ph.D., and Jack A. Elias, M.D.
ABSTRACT
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.
