Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, 492010, India.
Protein J. 2020 Apr;39(2):133-144. doi: 10.1007/s10930-020-09886-0.
Gout is a common rheumatic condition caused due to increase in serum uric acid level (hyperuricemia). Uricase is for lowering the level of uric acid but unfortunately, it is not produced in humans due to evolutionary changes. Therefore, it is administered to humans from outside in case of the high uric acid level in blood. A different formulation of uricase from bacterial, fungal, and mammalian sources is present in the market for the treatment of hyperuricemia conditions. Uricase formulation showed immunogenic response due to the occurrence of hypersensitivity reaction during the treatment that results in poor patient compliance. The purpose of this study was to clarify the variation of Uricase immunogenicity from different sources. We have used some immunoinformatic approaches to analyze and understand some structural aspects of immunogenic and allergenic epitopes of Uricase by calculation of relative frequency for eleven global alleles. As per our knowledge, this is the first immunoinformatic study of Uricase (structural based immunogenicity prediction) that deciphered the high immunogenic nature of Uricase but no significant difference in immunogenicity was found among Uricase isolated from Aspergillus flavus, Bacillus subtillis, and mammalian source. This study gives a further lead to develop some methods (include bioengineering of less immunogenic version of the uricase or utilizing the homologous enzymes) for minimizing immune response or search new sources of uricase that could be less or non-immunogenic.
痛风是一种常见的风湿性疾病,由血清尿酸水平升高(高尿酸血症)引起。尿酸酶用于降低尿酸水平,但不幸的是,由于进化的变化,人类体内不产生尿酸酶。因此,在血液中尿酸水平升高的情况下,从外部将其施用于人类。市场上有来自细菌、真菌和哺乳动物来源的不同尿酸酶制剂可用于治疗高尿酸血症。由于在治疗过程中发生过敏反应,尿酸酶制剂表现出免疫原性反应,导致患者顺应性差。本研究旨在阐明不同来源的尿酸酶免疫原性的变化。我们使用了一些免疫信息学方法,通过计算十一个全球等位基因的相对频率,来分析和理解尿酸酶免疫原性和过敏原表位的一些结构方面。据我们所知,这是尿酸酶(基于结构的免疫原性预测)的首次免疫信息学研究,该研究揭示了尿酸酶的高免疫原性,但从黄曲霉、枯草芽孢杆菌和哺乳动物来源分离的尿酸酶之间没有发现免疫原性的显著差异。这项研究为开发一些方法(包括生物工程改造尿酸酶的低免疫原性版本或利用同源酶)提供了进一步的依据,以最小化免疫反应或寻找新的尿酸酶来源,这些来源可能具有较低或非免疫原性。