目的：间质性肺病可见于多发性肌炎/皮肌炎(PM/DM)且与预后不良相关。壳多糖酶3样-1蛋白(YKL-40)具有多种生物学活性参与炎症反应、细胞增殖和组织重建。但是，YKL-40的临床应用仍然有限。我们研究YKL-40在PM/DM相关间质性肺病的临床意义。

方法：69例PM/DM相关间质性肺病和34例健康对照组进行分析。我们采用ELISA方法测定基线和随访中血清YKL-40并评估YKL-40与临床变量及存活的相关性。采用免疫组织化学法测定PM/DM相关间质性肺病患者肺组织YKL-40的表达。

结果：与健康对照组相关，PM/DM相关间质性肺病患者血清YKL-40水平显著升高(p<0.0001)。PM/DM相关间质性肺病患者中，血清YKL-40水平与动脉氧分压(r=-0.40，p<0.001)和百分比预测DLCO(r=-0.41，p=0.01)相关。Cox多元回归分析表明血清YKL-40水平升高和较低的用力肺活量(FVC)百分比预计值是预后不佳的独立危险因素。在PM/DM相关间质性肺病患者中，免疫组织化学法分析表明在肺泡内巨噬细胞和增殖的肺泡上皮细胞中YKL-40表达增强。

结论：YKL-40是评估PM/DM患者相关间质性肺病活动性和严重性的有前景的生物标志物并能够预测疾病预后。YKL-40的研究可能有助于阐明PM/DM相关间质性肺病的发病机制。

附原文

OBJECTIVE:Interstitial lung disease (ILD) is involved in polymyositis/dermatomyositis (PM/DM), a disease associated with poor prognoses. Chitinase-3-like-1 protein (YKL-40) has pleiotropic biological activities involved in inflammation, cell proliferation, and tissue remodeling; however, the clinical application of YKL-40 remains limited. We investigated the clinical significance of YKL-40 in PM/DM-ILD.METHODS:Sixty-nine consecutive patients with PM/DM-ILD and 34 healthy controls were analyzed. We measured baseline and followup serum YKL-40 using an ELISA, evaluated the association of YKL-40 with clinical variables and survival, and examined YKL-40 expression in lung specimens from patients with PM/DM-ILD using immunohistochemistry.RESULTS:Serum YKL-40 levels were significantly greater in patients with PM/DM-ILD compared with healthy controls (p < 0.0001). Serum YKL-40 was correlated with arterial oxygen pressure (r = -0.40, p < 0.001) and percent-predicted DLCO (r = -0.41, p = 0.01) in patients with PM/DM-ILD. Multivariate Cox hazard analysis demonstrated that higher serum YKL-40 and lower percent-predicted forced vital capacity were independently associated with a poor prognosis. Immunohistochemistry analysis demonstrated that YKL-40 expression was enhanced in aggregated intraalveolar macrophages and hyperproliferative alveolar epithelial cells in patients with PM/DM-ILD.CONCLUSION:YKL-40 is a promising biomarker for evaluating PM/DM-ILD activity/severity and predicting disease prognosis. Insights into YKL-40 might help elucidate the pathogenesis of PM/DM-ILD.

引自

Hozumi H,Fujisawa T,Enomoto N,et al.Clinical Utility of YKL-40 in Polymyositis/dermatomyositis-associated Interstitial Lung Disease.J Rheumatol.2017 Jul 15. pii: jrheum.170373. doi: 10.3899/jrheum.170373. [Epub ahead of print]