Institute of Clinical Neuroimmunology, Biomedical Center and Klinikum Grosshadern, Ludwig Maximilian University, Munich, Germany; Department of Neurology, Klinikum Grosshadern, Ludwig Maximilian University, Munich, Germany; Department of Medicine III, Klinikum Grosshadern, Ludwig Maximilian University, Munich, Germany.
Neuro Oncol. 2017 Nov 29;19(12):1618-1627. doi: 10.1093/neuonc/nox097.
B-cell survival is regulated through interactions of B-cell-activating factor and a proliferation-inducing ligand with their receptors transmembrane activator and CAML interactor (TACI) and B-cell maturation antigen (BCMA). We evaluated the diagnostic potential of soluble TACI (sTACI) and soluble BCMA (sBCMA) in CSF and serum as biomarkers in primary CNS lymphoma (PCNSL).
CSF (n = 176) and serum samples (n = 105) from patients with clinically or radiologically suspected PCNSL as well as from control patients were collected prospectively. Levels of sTACI and sBCMA were analyzed by enzyme-linked immunosorbent assay. Additionally, in patients with PCNSL, CSF was analyzed during disease course (time of diagnosis, n = 26; relapse, n = 10; remission, n = 14), and in 2 patients long-term longitudinal analysis was performed.
Soluble TACI and sBCMA are significantly increased in patients with PCNSL (sTACI, median: 445 pg/mL; sBCMA, median: 760 pg/mL) compared with control patients (sTACI, median: 0 pg/mL; sBCMA, median: 290 pg/mL). At a cutoff value of 68.4 pg/mL, sTACI shows high sensitivity (87.9%) and specificity (88.3%) for the diagnosis of active PCNSL. Soluble BCMA is less sensitive (72.7%) and specific (71.8%) (cutoff: 460 pg/mL). When both markers are combined, specificity increases, however, at the cost of a lower sensitivity. In serum, both sTACI and sBCMA are not increased in PCNSL patients. Both soluble receptors correlate with clinical course and therapy response.
Our results suggest that sTACI and sBCMA in the CSF are promising new biomarkers for diagnosis and therapy monitoring in PCNSL. However, our findings need to be validated in an independent cohort.
B 细胞的存活是通过 B 细胞激活因子和增殖诱导配体与其受体跨膜激活剂和钙调蛋白相互作用因子（TACI）和 B 细胞成熟抗原（BCMA）的相互作用来调节的。我们评估了脑脊液（CSF）和血清可溶性 TACI（sTACI）和可溶性 BCMA（sBCMA）作为原发性中枢神经系统淋巴瘤（PCNSL）生物标志物的诊断潜力。
前瞻性收集了临床或影像学怀疑为 PCNSL 的患者（n = 176）以及对照患者的 CSF（n = 105）和血清样本。通过酶联免疫吸附试验分析 sTACI 和 sBCMA 的水平。此外，在 PCNSL 患者中，在疾病过程中分析 CSF（诊断时，n = 26；复发时，n = 10；缓解时，n = 14），并对 2 例患者进行了长期纵向分析。
与对照患者相比（sTACI 中位数：0 pg/mL；sBCMA 中位数：290 pg/mL），PCNSL 患者的 sTACI 和 sBCMA 显著升高（sTACI 中位数：445 pg/mL；sBCMA 中位数：760 pg/mL）。当以 68.4 pg/mL 为截断值时，sTACI 对活动性 PCNSL 的诊断具有高灵敏度（87.9%）和特异性（88.3%）。sBCMA 的灵敏度较低（72.7%）和特异性（71.8%）（截断值：460 pg/mL）。当两种标志物结合使用时，特异性增加，但灵敏度降低。在血清中，PCNSL 患者的 sTACI 和 sBCMA 均未升高。两种可溶性受体均与临床病程和治疗反应相关。
我们的研究结果表明，CSF 中的 sTACI 和 sBCMA 是 PCNSL 诊断和治疗监测的有前途的新型生物标志物。然而，我们的发现需要在独立队列中得到验证。
