Wurth Sebastian, Kuenz Bettina, Bsteh Gabriel, Ehling Rainer, Di Pauli Franziska, Hegen Harald, Auer Michael, Gredler Viktoria, Deisenhammer Florian, Reindl Markus, Berger Thomas
Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Tirol, Austria.
Department of Neurology, Clinic for Rehabilitation Münster, Münster, Tirol, Austria.
PLoS One. 2017 Aug 4;12(8):e0182462. doi: 10.1371/journal.pone.0182462. eCollection 2017.
There is evidence that B cells play an important role in disease pathology of multiple sclerosis (MS). The aim of this prospective observational study was to determine the predictive value of cerebrospinal fluid (CSF) B cell subtypes in disease evolution of patients with MS.
128 patients were included between 2004 and 2012. Median follow up time was 7.9 years (range 3.3-10.8 years). 10 patients were lost to follow-up. 32 clinically isolated syndrome- (CIS), 25 relapsing remitting MS- (RRMS), 2 secondary progressive MS- (SPMS) and 9 primary progressive MS- (PPMS) patients were included. The control group consisted of 40 patients with other neurological diseases (OND). CSF samples were analyzed for routine diagnostic parameters. B cell phenotypes were characterized by flow cytometry using CD19 and CD138 specific antibodies. Standardized baseline brain MRI was conducted at the time of diagnostic lumbar puncture. Main outcome variables were likelihood of progressive disease course, EDSS progression, conversion to clinical definite MS (CDMS) and relapse rate.
CSF mature B cells (CD19+CD138-) were increased in bout-onset MS compared to PPMS (p<0.05) and OND (p<0.001), whereas plasma blasts (CD19+CD138+) were increased in bout-onset MS (p<0.001) and PPMS (p<0.05) compared to OND. CSF B cells did not predict a progressive disease course, EDSS progression, an increased relapse rate or the conversion to CDMS. Likelihood of progressive disease course (p<0.05) and EDSS (p<0.01) was predicted by higher age at baseline, whereas conversion to CDMS was predicted by a lower age at onset (p<0.01) and the presence of ≥9 MRI T2 lesions (p<0.05).
We detected significant differences in the CSF B cell subsets between different clinical MS subtypes and OND patients. CSF B cells were neither predictive for disease and EDSS progression nor conversion to CDMS after a CIS.
有证据表明B细胞在多发性硬化症(MS)的疾病病理学中起重要作用。这项前瞻性观察性研究的目的是确定脑脊液(CSF)B细胞亚群在MS患者疾病进展中的预测价值。
2004年至2012年纳入128例患者。中位随访时间为7.9年(范围3.3 - 10.8年)。10例患者失访。纳入32例临床孤立综合征(CIS)、25例复发缓解型MS(RRMS)、2例继发进展型MS(SPMS)和9例原发进展型MS(PPMS)患者。对照组由40例其他神经系统疾病(OND)患者组成。对脑脊液样本进行常规诊断参数分析。使用CD19和CD138特异性抗体通过流式细胞术对B细胞表型进行表征。在诊断性腰椎穿刺时进行标准化的基线脑部MRI检查。主要结局变量为疾病进展病程的可能性、扩展残疾状态量表(EDSS)进展、转化为临床确诊MS(CDMS)以及复发率。
与PPMS(p<0.05)和OND(p<0.001)相比,发作性MS患者脑脊液中的成熟B细胞(CD19 + CD138 -)增加,而与OND相比,发作性MS(p<0.001)和PPMS(p<0.05)患者的浆细胞(CD19 + CD138 +)增加。脑脊液B细胞不能预测疾病进展病程、EDSS进展、复发率增加或转化为CDMS。基线时年龄较大可预测疾病进展病程的可能性(p<0.05)和EDSS(p<0.01),而发病时年龄较小(p<0.01)和存在≥9个MRI T2病变(p<0.05)可预测转化为CDMS。
我们检测到不同临床MS亚型与OND患者之间脑脊液B细胞亚群存在显著差异。脑脊液B细胞既不能预测疾病和EDSS进展,也不能预测CIS后转化为CDMS。