Enzyme replacement therapy (ERT) for Fabry disease (deficiency of α-galactosidase A, α-Gal) with recombinant α-Gals (agalsidase alfa and agalsidase beta) is widely available and improves some of the clinical manifestations and biochemical findings. However, recent reports suggest that recurrent administration of recombinant enzymes often induces the formation of anti-drug antibodies, which may have a negative impact on the outcome of the therapy. We examined the formation of anti-drug antibodies using blood samples from 97 Japanese Fabry patients following ERT and tried to characterize them by means of enzyme-linked immunosorbent assay (ELISA), serum-mediated α-Gal inhibition, and immunochromatographic (IC) assay, followed by GLA gene analysis and measurement of plasma globotriaosylsphingosine (lyso-Gb3). ELISA revealed that 20/35 (57%) classic Fabry males were antibody (Immunoglobulin G, IgG) -positive (Ab+) at 6 months after the initiation of ERT, although only two of the seventeen (12%) later-onset Fabry males and none of the 45 Fabry females were. The Ab+ state was maintained at least until 24 months after the initiation of ERT in most of the cases, the exceptions being two patients who acquired immune tolerance during ERT. As many Ab+ patients have nonsense mutations, attention should be paid to the formation of anti-drug antibodies in Fabry patients harboring such gene mutations, who hardly produce α-Gal protein. Serum-mediated α-Gal inhibition was seen in most of the Ab+ patients and the antibodies affected the reduction of the plasma lyso-Gb3 level following ERT, suggesting that the antibodies inhibit the enzyme activity. There was a correlation between the results of the IC test and those of the ELISA. As the former is easy and rapid, it should be useful as a bed-side test.

用重组α-Gal（阿加糖苷酶α和阿加糖苷酶β）进行法布里病（α-半乳糖苷酶A，α-Gal缺乏症）的酶替代疗法（ERT）已广泛使用，并改善了一些临床表现和生化发现。但是，最近的报道表明，重组酶的反复给药通常会诱导抗药物抗体的形成，这可能对治疗结果产生负面影响。我们使用来自ERT后的97位日本Fabry患者的血液样本检查了抗药物抗体的形成，并试图通过酶联免疫吸附测定（ELISA），血清介导的α-Gal抑制和免疫色谱（IC）测定来表征它们，其次是GLA血浆globotriaosylsphingosine（lyso-Gb3）的基因分析和测量。ELISA显示，在ERT发病后6个月，有20/35（57％）的经典Fabry雄性抗体（免疫球蛋白G，IgG）呈阳性（Ab +），尽管在后来发病的17名（12％）法布里雄性中只有2个而45名法布里女性中都没有。在大多数情况下，Ab +状态至少要维持到ERT开始后的24个月，例外是两名在ERT期间获得免疫耐受的患者。由于许多Ab +患者具有无意义的突变，因此应注意具有此类基因突变且几乎不产生α-Gal蛋白的法布里患者中抗药物抗体的形成。在大多数Ab +患者中观察到血清介导的α-Gal抑制作用，并且抗体影响ERT后血浆溶血Gb3水平的降低，提示抗体抑制了酶的活性。IC测试结果和ELISA结果之间存在相关性。由于前者既简单又快速，因此在床旁测试中应该很有用。