Belén Lisandra Herrera, Lissabet Jorge Beltrán, de Oliveira Rangel-Yagui Carlota, Effer Brian, Monteiro Gisele, Pessoa Adalberto, Farías Avendaño Jorge G
Department of Chemical Engineering, Faculty of Engineering and Science, Universidad de La Frontera, Temuco, Chile.
Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Biologicals. 2019 May;59:47-55. doi: 10.1016/j.biologicals.2019.03.003. Epub 2019 Mar 11.
Acute lymphoblastic leukemia (ALL) is a type of cancer with a high incidence in children. The enzyme l-asparaginase (ASNase) constitutes a key element in the treatment of this disease. Four formulations of ASNase from a bacterial source are currently available. However, these formulations are characterized by their high immunogenicity, resulting in the inactivation of the drug, as well as in the occurrence of hypersensitivity reactions in a large number of patients. In this work, we performed an immunoinformatic analysis in order to clarify structural aspects of the immunogenicity of the asparaginase from Escherichia coli and Erwinia carotovora. For this purpose, we performed the prediction of immunogenic and allergenic epitopes in the structure of asparaginases by using the relative frequency of immunogenic peptides for the eight alleles most frequently distributed worldwide. This study showed that there are no significant differences in the level of immunogenicity between the two enzymes, while asparaginase from E. coli presented a higher relative frequency of allergenic epitopes. These results are consistent with previously published reports. However, from a structural point of view, to the best of our knowledge, this is the first report describing the structural determinants that contribute to the hypersensitivity response to this treatment.
急性淋巴细胞白血病（ALL）是一种在儿童中发病率较高的癌症。L-天冬酰胺酶（ASNase）是治疗这种疾病的关键要素。目前有四种来源于细菌的ASNase制剂。然而，这些制剂的特点是免疫原性高，导致药物失活，并且在大量患者中出现过敏反应。在这项工作中，我们进行了免疫信息学分析，以阐明大肠杆菌和胡萝卜软腐欧文氏菌中天冬酰胺酶免疫原性的结构方面。为此，我们通过使用全球分布最频繁的八个等位基因的免疫原性肽的相对频率，对天冬酰胺酶结构中的免疫原性和过敏原表位进行了预测。这项研究表明，两种酶之间的免疫原性水平没有显著差异，而大肠杆菌来源的天冬酰胺酶呈现出更高的过敏原表位相对频率。这些结果与先前发表的报告一致。然而，据我们所知，从结构角度来看，这是第一份描述导致对这种治疗产生过敏反应的结构决定因素的报告。
