Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study.
Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study.
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DOI：
10.1186/1471-2377-7-3
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发表时间：
2007-01-29
期刊：
影响因子：
2.6
通讯作者：
Gahl WA
中科院分区：
文献类型：
--
作者：
Sparks S;Rakocevic G;Joe G;Manoli I;Shrader J;Harris-Love M;Sonies B;Ciccone C;Dorward H;Krasnewich D;Huizing M;Dalakas MC;Gahl WA
遗传性包涵体肌病（HIBM）是一种常染色体隐性遗传、成人发病、非炎性神经肌肉疾病，目前尚无有效治疗方法。致病基因GNE编码UDP-N-乙酰葡糖胺2-差向异构酶/N-乙酰甘露糖胺激酶，其催化唾液酸合成中的前两个反应。在HIBM中报告了肌糖蛋白（如α-肌营养不良蛋白聚糖和神经细胞粘附分子（NCAM））的唾液酸化减少。我们用静脉注射免疫球蛋白（IVIG）治疗4例HIBM患者，以提供唾液酸，因为IgG含有8 μ mol唾液酸/g。IVIG以1 g/kg的负荷剂量连续两天输注，然后以每周一次的间隔输注3次400 mg/kg剂量。对于所有4名患者，平均股四头肌力量从基线时的19.0 kg改善到IVIG负荷后的23.2 kg（+22%），研究结束时为25.6 kg（+35%）。平均肩部力量从基线时的4.1 kg提高到IVIG负荷后的5.9 kg（+44%），在研究结束时提高到6.0 kg（+46%）。其他8个肌肉群的复合改善在初始负荷后为5%，在研究结束时为19%。钡剂异常患者食管运动和舌强度改善。功能改善的客观指标给出了不同的结果，但患者的日常活动得到了改善，他们认为这些改善具有临床意义。肌活检α-肌营养不良蛋白聚糖和NCAM的免疫组织化学染色和免疫印迹未提供IVIG治疗后唾液酸化增加的一致证据。副作用仅限于短暂的头痛和呕吐。IVIG治疗后HIBM患者肌肉力量的轻度获益可能与IVIG提供的唾液酸有关。正在探索其他来源的唾液酸作为HIBM的治疗选择。
Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.
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DOI：
10.1073/pnas.82.13.4544
发表时间：
1985-01-01
影响因子：
11.1
作者：
COVAULT, J;SANES, JR
通讯作者：
SANES, JR
DOI：
10.1111/j.1532-5415.2004.52366.x
发表时间：
2004-08-01
影响因子：
6.3
作者：
Lin, MR;Hwang, HF;Huang, FC
通讯作者：
Huang, FC
DOI：
10.1046/j.1432-1327.1998.2520133.x
发表时间：
1998-02-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Hinderlich, S;Nöhring, S;Reuter, W
通讯作者：
Reuter, W
影响因子：
9.9
作者：
Argov, Z;Eisenberg, L;Mitrani-Rosenbaum, S
通讯作者：
Mitrani-Rosenbaum, S
影响因子：
3.4
作者：
Del Bo, R;Baron, P;Comi, GP
通讯作者：
Comi, GP