In Pompe disease, anti-drug antibodies (ADA) to acid alpha-glucosidase (GAA) enzyme replacement therapy contribute to early mortality. Assessing individual risk for ADA development is notoriously difficult in (CRIM-positive) patients expressing endogenous GAA. The individualized T cell epitope measure (iTEM) scoring method predicts patient-specific risk of developing ADA against therapeutic recombinant human GAA (rhGAA) using individualized HLA-binding predictions and GAA genotype. CRIM-negative patients were six times more likely to develop high ADA titers than CRIM-positive patients in this retrospective study, whereas patients with high GAA-iTEM scores were 50 times more likely to develop high ADA titers than patients with low GAA-iTEM scores. This approach identifies high-risk IOPD patients requiring immune tolerance induction therapy to prevent significant ADA response to rhGAA leading to a poor clinical outcome and can assess ADA risk in patients receiving replacement therapy for other enzyme or blood factor deficiency disorders.

中文翻译：

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基于HLA和基于基因型的风险评估模型，可识别处于发展显着抗药物抗体（ADA）高风险的婴儿发作性庞贝病患者。

在庞贝病中，针对酸性α-葡萄糖苷酶（GAA）酶替代疗法的抗药物抗体（ADA）有助于早期死亡。在表达内源性GAA的（CRIM阳性）患者中，评估ADA发展的个体风险非常困难。个性化的T细胞表位测量（iTEM）评分方法使用个性化的HLA结合预测和GAA基因型，预测针对治疗性重组人GAA（rhGAA）的​​ADA患者发展的特异性风险。在这项回顾性研究中，CRIM阴性患者出现高ADA滴度的可能性是CRIM阳性患者的六倍，而GAA-iTEM得分高的患者发生ADA高滴度的可能性是GAA-iTEM得分低的患者高50倍。