Brady R O, Murray G J, Oliver K L, Leitman S F, Sneller M C, Fleisher T A, Barton N W
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20852-1260, USA.
Pediatrics. 1997 Dec;100(6):E11. doi: 10.1542/peds.100.6.e11.
The beneficial effects of macrophage-targeted glucocerebrosidase (Ceredase) in patients with Gaucher disease are well established. A minority of recipients develop transient nonneutralizing antibodies to the exogenous enzyme. A 7-year-old patient with type 3 Gaucher disease whose clinical course began to deteriorate while receiving Ceredase developed a progressively increasing titer of IgG antibody that blocked the catalytic activity of Ceredase. We sought to develop a strategy that would restore the benefit of enzyme replacement therapy in this patient.
The patient was treated with two courses of a combination of plasma exchange, cyclophosphamide, intravenous IgG, and large doses of Ceredase.
After the second course of this regimen, the titer of the neutralizing antibody in the blood gradually declined to negligible levels. Clinical parameters that had been deteriorating (reduction of hemoglobin level, increased serum acid phosphates activity, repeated skeletal infarctions, progressive enlargement and infarction of the spleen) all improved. There has been no recurrence of the neutralizing antibody in this patient.
Very few patients with Gaucher disease who are treated with Ceredase develop a neutralizing antibody to the exogenous enzyme. In the rare instances where this phenomenon occurs, it is likely that the strategy we have used (plasma exchange, cyclophosphamide, intravenous IgG, and large doses of enzyme) may provide benefit to such individuals. It is also likely that this technique may be helpful when enzyme replacement therapy is attempted in patients with other disorders in which the genetic mutation abrogates the production of the protein (CRIM-negative individuals).
巨噬细胞靶向性葡糖脑苷脂酶（思而赞）对戈谢病患者的有益作用已得到充分证实。少数接受者会产生针对外源性酶的短暂非中和抗体。一名3型戈谢病患儿在接受思而赞治疗期间临床病程开始恶化，其IgG抗体滴度逐渐升高，该抗体可阻断思而赞的催化活性。我们试图制定一种策略来恢复该患者酶替代疗法的益处。
该患者接受了两个疗程的血浆置换、环磷酰胺、静脉注射免疫球蛋白和大剂量思而赞联合治疗。
在该治疗方案的第二个疗程后，血液中中和抗体的滴度逐渐降至可忽略不计的水平。此前一直恶化的临床参数（血红蛋白水平降低、血清酸性磷酸酶活性升高、反复发生骨骼梗死、脾脏进行性肿大和梗死）均有所改善。该患者未再出现中和抗体。
接受思而赞治疗的戈谢病患者中，很少有人会产生针对外源性酶的中和抗体。在这种罕见现象发生的情况下，我们所采用的策略（血浆置换、环磷酰胺、静脉注射免疫球蛋白和大剂量酶）可能对此类患者有益。当对其他因基因突变导致蛋白质产生缺失的疾病（CRIM阴性个体）患者尝试进行酶替代治疗时，这种技术也可能会有所帮助。
