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白蛋白水平与静脉注射免疫球蛋白治疗的吉兰-巴雷综合征结局的相关性。

Association of Albumin Levels With Outcome in Intravenous Immunoglobulin-Treated Guillain-Barré Syndrome.

机构信息

Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands2Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

出版信息

JAMA Neurol. 2017 Feb 1;74(2):189-196. doi: 10.1001/jamaneurol.2016.4480.

Abstract

IMPORTANCE

There is an urgent need for biomarkers to monitor treatment efficacy and anticipate outcome in patients with Guillain-Barré syndrome (GBS).

OBJECTIVE

To assess whether there is an association between serum albumin levels, a widely used and relatively easily measurable biomarker of health and inflammation, and the clinical course and outcome of GBS in patients treated with intravenous immunoglobulin (IVIG).

DESIGN, SETTING, AND PARTICIPANTS: We used serum samples derived from a cohort of patients with GBS admitted to hospitals across the Netherlands participating in national GBS studies from May 5, 1986, through August 2, 2000. Serum albumin was measured from January 13 to 20, 2011. Analysis was performed from February 25, 2013, to September 6, 2016. All patients fulfilled the criteria for GBS and had severe disease (defined as not being able to walk unaided >10 m). Patients misdiagnosed as having GBS were retrospectively excluded from the study. Serum samples were obtained before and after IVIG treatment at 4 standardized time points from 174 patients. Albumin levels were determined by routine diagnostic turbidimetry and related to demographics and clinical course during a follow-up of 6 months.

MAIN OUTCOMES AND MEASURES

Serum albumin concentration was determined before and after treatment with IVIG and related to clinical outcome: muscle weakness (measured by Medical Research Council sum score), respiratory failure (measured by requirement and duration of mechanical ventilation), and ability to walk (measured by GBS disability score).

RESULTS

Serum albumin levels were determined in 174 patients with GBS (mean [SD] age, 49.6 [20.1] years; 99 males [56.9%]). Before treatment, the median serum albumin level was 4.2 g/dL (interquartile range, 3.8-4.5 g/dL), with hypoalbuminemia (albumin, <3.5 g/dL) in 20 (12.8%) of 156 patients. Two weeks after commencing treatment with IVIG (2 g/kg), the median serum albumin level decreased to 3.7 g/dL (interquartile range, 3.2-4.1 g/dL) (P < .001), and the number with hypoalbuminemia increased to 60 (34.5%) of 174 (P < .001). Hypoalbuminemia was associated with an increased chance of respiratory failure before (16 [36.4%] of 44, P = .001) or after (29 [54.7%] of 53, P < .001) IVIG treatment, inability to walk unaided (21 [35.0%] of 60 vs 6 [5.3%] of 114, P < .001), and severe muscle weakness at 4 weeks (Medical Research Council sum score, 31.8 vs 52.9, P < .001) and 6 months (Medical Research Council sum score, 49.4 vs 58.4, P < .001).

CONCLUSIONS AND RELEVANCE

Patients with GBS may develop hypoalbuminemia after treatment with IVIG, which is related to a more severe clinical course and a poorer outcome. Further studies are required to confirm that serum albumin can be used as a biomarker to monitor disease activity and treatment response to IVIG in patients with GBS.

摘要

重要性:目前急需生物标志物来监测治疗效果并预测 Guillain-Barré 综合征(GBS)患者的预后。

目的:评估血清白蛋白水平(一种广泛使用且相对容易测量的健康和炎症标志物)与接受静脉注射免疫球蛋白(IVIG)治疗的 GBS 患者的临床病程和结局之间是否存在关联。

设计、地点和参与者:我们使用来自荷兰多家医院的 GBS 患者队列的血清样本,这些患者参与了 1986 年 5 月 5 日至 2000 年 8 月 2 日期间的全国性 GBS 研究。血清白蛋白于 2011 年 1 月 13 日至 20 日测量。分析于 2013 年 2 月 25 日至 2016 年 9 月 6 日进行。所有患者均符合 GBS 标准且患有严重疾病(定义为不能独立行走超过 10 米)。将误诊为 GBS 的患者从研究中排除。从 174 名患者的 4 个标准化时间点获得 IVIG 治疗前后的血清样本。白蛋白水平通过常规诊断比浊法确定,并与 6 个月随访期间的人口统计学和临床病程相关。

主要结局和测量指标:确定 GBS 患者接受 IVIG 治疗前后的血清白蛋白浓度,并与临床结局相关:肌肉无力(通过医学研究理事会总评分测量)、呼吸衰竭(通过机械通气的需求和持续时间测量)和独立行走能力(通过 GBS 残疾评分测量)。

结果:我们对 174 名 GBS 患者(平均[标准差]年龄为 49.6[20.1]岁;男性 99 名[56.9%])进行了血清白蛋白水平检测。治疗前,中位血清白蛋白水平为 4.2 g/dL(四分位距,3.8-4.5 g/dL),156 名患者中有 20 名(12.8%)存在低蛋白血症(白蛋白<3.5 g/dL)。开始接受 2 g/kg IVIG 治疗后 2 周,中位血清白蛋白水平降至 3.7 g/dL(四分位距,3.2-4.1 g/dL)(P<0.001),低蛋白血症患者增加至 60 名(34.5%)(P<0.001)。低蛋白血症与 IVIG 治疗前(44 名患者中有 16 名[36.4%],P=0.001)或治疗后(53 名患者中有 29 名[54.7%],P<0.001)呼吸衰竭、无法独立行走(60 名患者中有 21 名[35.0%],114 名患者中有 6 名[5.3%],P<0.001)和 4 周时严重肌肉无力(医学研究理事会总评分,31.8 比 52.9,P<0.001)和 6 个月时(医学研究理事会总评分,49.4 比 58.4,P<0.001)相关。

结论和相关性:接受 IVIG 治疗后,GBS 患者可能会出现低蛋白血症,这与更严重的临床病程和较差的预后有关。需要进一步研究以确认血清白蛋白是否可以作为监测疾病活动和 IVIG 治疗反应的生物标志物,用于 GBS 患者。

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