CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma
CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma
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DOI：
10.1182/blood-2013-01-476333
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发表时间：
2013-06-06
期刊：
影响因子：
20.3
通讯作者：
Lowell, Clifford
中科院分区：
文献类型：
--
作者：
Rubenstein, James L.;Wong, Valerie S.;Lowell, Clifford
在有不明原因的神经系统症状的患者中建立局灶性脑病变的诊断是一个挑战。本研究的目的是为CXC趋化因子配体（CXCL） 13和白细胞介素(IL)-10在中枢神经系统（CNS）淋巴瘤中的功能作用提供证据，并评估它们作为预后和诊断生物标志物的效用。我们首次证明脑脊液（CSF）中CXCL13浓度升高具有预后作用，并且CXCL13和CXCL12介导从中枢神经系统淋巴瘤病变中分离的淋巴瘤细胞的趋化性。Janus激酶1活化形式的表达支持IL-10在促生存信号传导中的作用。在一项涉及220例患者的多中心研究中，我们测定了中枢神经系统淋巴瘤患者CSF中CXCL13和IL-10的浓度以及包括炎症和退行性神经系统疾病的对照队列。双变量升高的CXCL13 + IL-10对原发性和继发性中枢神经系统淋巴瘤的特异性为99.3%，敏感性显著高于参考标准CSF试验。这些结果确定CXCL13和IL-10是中枢神经系统淋巴瘤的潜在重要生物标志物，值得进一步评估，并支持将CXCL13和IL-10纳入考虑淋巴瘤的局灶性脑病变的诊断算法。
Establishing the diagnosis of focal brain lesions in patients with unexplained neurologic symptoms represents a challenge. The goal of this study is to provide evidence supporting functional roles for CXC chemokine ligand (CXCL) 13 and interleukin (IL)-10 in central nervous system (CNS) lymphomas and to evaluate the utility of each as prognostic and diagnostic biomarkers. We demonstrate for the first time that elevated CXCL13 concentration in cerebrospinal fluid (CSF) is prognostic and that CXCL13 and CXCL12 mediate chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. Expression of the activated form of Janus kinase 1 supported a role for IL-10 in prosurvival signaling. We determined the concentration of CXCL13 and IL-10 in CSF of CNS lymphoma patients and control cohorts including inflammatory and degenerative neurologic disease in a multicenter study involving 220 patients. Bivariate elevated CXCL13 plus IL-10 was 99.3% specific for primary and secondary CNS lymphoma, with sensitivity significantly greater than reference standard CSF tests. These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration.