Early diagnosis of CNS lymphoma (CNSL) is essential for successful therapy of this rapidly progressing brain tumor. However, in patients presenting with focal brain lesions, fast and reliable diagnosis of PCNSL remains a challenge. A proliferation-inducing ligand (APRIL) and B cell activating factor (BAFF) are important factors in the pathophysiology, diagnosis, and prognosis of systemic B cell malignancies. However, their utility as biomarkers for the diagnosis of CNSL and their effects on CNSL cells remain unclear. In this prospective study, we analyzed the levels of APRIL and BAFF in the cerebrospinal fluid (CSF) of 116 patients with suspected focal brain lesions, including 53 CNSL patients. Additionally, we serially measured their levels during chemotherapy and relapse. Furthermore, we analyzed the effect of APRIL and BAFF on two B cell lymphoma cell lines using proliferation, viability, and chemotaxis assays. CSF levels of APRIL and BAFF reliably differentiated CNSL from other focal brain lesions (including primary and metastatic brain tumors, autoimmune-inflammatory lesions, and neuroinfectious lesions) with a specificity of 93.7% (APRIL, BAFF) and a sensitivity of 62.3% (APRIL) and 47.1% (BAFF). Serial CSF analysis of CNSL patients during chemotherapy and relapse demonstrates a close correlation of APRIL CSF levels and the course of this disease. In vitro, APRIL and BAFF showed anti-apoptotic effects during MTX treatment and mediated chemotaxis of malignant B cells. This study extends the spectrum of valuable diagnostic biomarkers in CNSL. In patients with focal brain lesions, measurement of APRIL in CSF could help accelerating the diagnosis of CNSL. Moreover, our results highlight an important role of APRIL and BAFF in the pathophysiology of CNSL.

中文翻译：

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4月和BAFF：中枢神经系统淋巴瘤的新型生物标志物。

CNS淋巴瘤（CNSL）的早期诊断对于成功治疗这种迅速发展的脑肿瘤至关重要。然而，在存在局灶性脑损伤的患者中，快速，可靠地诊断PCNSL仍然是一个挑战。诱导增殖的配体（APRIL）和B细胞活化因子（BAFF）是系统性B细胞恶性肿瘤的病理生理学，诊断和预后的重要因素。然而，它们作为生物标志物用于诊断CNSL及其对CNSL细胞的作用的用途仍不清楚。在这项前瞻性研究中，我们分析了116例怀疑有局灶性脑病变的患者（包括53例CNSL患者）的脑脊液（CSF）中APRIL和BAFF的水平。此外，我们在化疗和复发期间连续测量了它们的水平。此外，我们使用增殖，生存力和趋化性分析法分析了APRIL和BAFF对两种B细胞淋巴瘤细胞系的影响。脑脊液中APRIL和BAFF的水平可靠地将CNSL与其他局灶性脑病变（包括原发性和转移性脑肿瘤，自身免疫炎性病变和神经感染性病变）区分开，特异性为93.7％（APRIL，BAFF），敏感性为62.3％（APRIL） ）和47.1％（BAFF）。在化疗和复发期间对CNSL患者进行的连续CSF分析表明，APRIL CSF水平与该病的病程密切相关。在体外，APRIL和BAFF在MTX治疗期间显示出抗凋亡作用，并介导了恶性B细胞的趋化性。这项研究扩展了CNSL中有价值的诊断生物标志物的范围。在患有局灶性脑损伤的患者中，脑脊液中APRIL的测定有助于加速CNSL的诊断。此外，我们的结果突出了APRIL和BAFF在CNSL病理生理中的重要作用。