Gibbs D A, Spellacy E, Tompkins R, Watts R W, Mowbray J F
J Inherit Metab Dis. 1983;6(2):62-81. doi: 10.1007/BF02338973.
This paper reports the clinical and biochemical results in six patients with Hurler disease (Mucopolysaccharidosis IH; McKusick 25280), two patients with Hunter disease (Mucopolysaccharidosis II; McKusick 25285) and one patient with Sanfilippo B disease (Mucopolysaccharidosis IIIB; McKusick 25292) who were treated by fibroblast transplantation. Except for one patient who died for a coincidental reason, the patients have been studied for between 2.5 and 4.5 years. The clinical course of the disease was not materially altered. There was no evidence that the patients had developed immune responses against the transplanted fibroblasts. Transplantation did not produce measurable levels of either alpha-L-iduronidase (EC 3.2.1.76) in the leukocytes from patients with Hurler disease or of N-acetyl-alpha-D-glucosaminidase (EC 3.2.1.50) in the plasma of the patients with Sanfilippo B disease. Under the conditions used for the assay, leukocytes from the patients with Hunter disease had detectable levels of residual alpha-L-idurono-2-sulphate sulphatase activity which were increased after the transplants, although these changes were of inconstant size and their time course was not consistently related to the transplantations. Cytogenetic studies in cases where the donor was of the opposite sex detected only cells of the recipient's sex among the fibroblasts grown from biopsies of the transplantation sites. The technique used would have detected a donor to recipient cell ratio of 1:100. We found no consistent long-term trends in the excretion patterns of glycosaminoglycans and oligosaccharides from either a quantitative or qualitative point of view which could be specifically related to the transplantation. The combined administration of immunosuppressive doses of prednisolone and azathioprine was associated with an increased excretion of the lower molecular weight glycosaminoglycans. We conclude that fibroblast transplantation is not therapeutically useful in the diseases studied.
本文报告了6例Hurler病（黏多糖贮积症I型；McKusick 25280）、2例Hunter病（黏多糖贮积症II型；McKusick 25285）和1例Sanfilippo B病（黏多糖贮积症IIIB型；McKusick 25292）患者接受成纤维细胞移植后的临床和生化结果。除1例因意外原因死亡的患者外，其余患者的研究时间为2.5至4.5年。疾病的临床进程没有实质性改变。没有证据表明患者对移植的成纤维细胞产生了免疫反应。移植并未在Hurler病患者的白细胞中产生可测量水平的α-L-艾杜糖醛酸酶（EC 3.2.1.76），也未在Sanfilippo B病患者的血浆中产生可测量水平的N-乙酰-α-D-氨基葡萄糖苷酶（EC 3.2.1.50）。在所采用的检测条件下，Hunter病患者的白细胞具有可检测到的残余α-L-艾杜糖醛酸-2-硫酸酯酶活性水平，移植后有所增加，尽管这些变化大小不一，其时间进程与移植并无始终一致的关联。在供体为异性的病例中，细胞遗传学研究在移植部位活检培养的成纤维细胞中仅检测到受体性别的细胞。所采用的技术本可检测到供体与受体细胞比例为1:100的情况。从定量或定性角度来看，我们未发现糖胺聚糖和寡糖排泄模式存在与移植有特定关联的一致长期趋势。联合给予免疫抑制剂量的泼尼松龙和硫唑嘌呤与较低分子量糖胺聚糖排泄增加有关。我们得出结论，成纤维细胞移植对所研究的疾病无治疗作用。
