{"title":"Molecular Biological Aspects of Inhibitor Development","authors":"E.G.D. Tuddenham","doi":"10.1111/j.1423-0410.1999.tb00005.x","DOIUrl":null,"url":null,"abstract":"Mutation genotype studies have led to a number of interesting observations about the role of the different types of mutations in inhibitor development. Searchable information on mutations, phenotype data, models, etc., are available on the internet at <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://europium.mrc.rpms.ac.uk\">http://europium.mrc.rpms.ac.uk</jats:ext-link>. A relatively high incidence of inhibitors occurs in patients with deletion mutations. Stop mutations are also associated with a high incidence of inhibitors, although there is anomalous distribution of the inhibitors associated with different stop codons. Inhibitors have been associated with a small number of missense mutations. Missense mutations are of great interest from the structure/function viewpoint; in many instances, a missense mutation which results in reduced function of a circulating protein can be mapped onto a model structure and inferences can be made about the effects on the functionality of the protein. A model of the A domains of FVIII is available, but as yet, no structure is available on which to model the C domain of FVIII. Stop codons appear to have a different incidence of inhibitor formation compared to other types of mutations. It is concluded that while genotype mutation studies have led to a number of interesting observations about the role of the different types of mutations in inhibitor development, though more questions have been raised than answers provided to date.","PeriodicalId":23631,"journal":{"name":"Vox Sanguinis","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vox Sanguinis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/j.1423-0410.1999.tb00005.x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mutation genotype studies have led to a number of interesting observations about the role of the different types of mutations in inhibitor development. Searchable information on mutations, phenotype data, models, etc., are available on the internet at http://europium.mrc.rpms.ac.uk. A relatively high incidence of inhibitors occurs in patients with deletion mutations. Stop mutations are also associated with a high incidence of inhibitors, although there is anomalous distribution of the inhibitors associated with different stop codons. Inhibitors have been associated with a small number of missense mutations. Missense mutations are of great interest from the structure/function viewpoint; in many instances, a missense mutation which results in reduced function of a circulating protein can be mapped onto a model structure and inferences can be made about the effects on the functionality of the protein. A model of the A domains of FVIII is available, but as yet, no structure is available on which to model the C domain of FVIII. Stop codons appear to have a different incidence of inhibitor formation compared to other types of mutations. It is concluded that while genotype mutation studies have led to a number of interesting observations about the role of the different types of mutations in inhibitor development, though more questions have been raised than answers provided to date.
通过突变基因型研究,我们对不同类型的突变在抑制剂研发中的作用有了许多有趣的观察。有关突变、表型数据、模型等的可搜索信息可在互联网 http://europium.mrc.rpms.ac.uk 上获得。缺失突变患者的抑制剂发生率相对较高。终止突变也与抑制剂的高发病率有关,但不同终止密码子的抑制剂分布异常。抑制剂与少数错义突变有关。从结构/功能的角度来看,错义突变具有极大的意义;在许多情况下,导致循环蛋白功能降低的错义突变可以映射到模型结构上,从而推断出对蛋白功能的影响。目前已有 FVIII A 结构域的模型,但还没有 FVIII C 结构域的模型。与其他类型的突变相比,终止密码子形成抑制剂的几率似乎有所不同。结论是,虽然基因型突变研究对不同类型的突变在抑制剂形成中的作用提出了许多有趣的看法,但迄今为止提出的问题比给出的答案要多。
期刊介绍:
Vox Sanguinis reports on important, novel developments in transfusion medicine. Original papers, reviews and international fora are published on all aspects of blood transfusion and tissue transplantation, comprising five main sections:
1) Transfusion - Transmitted Disease and its Prevention:
Identification and epidemiology of infectious agents transmissible by blood;
Bacterial contamination of blood components;
Donor recruitment and selection methods;
Pathogen inactivation.
2) Blood Component Collection and Production:
Blood collection methods and devices (including apheresis);
Plasma fractionation techniques and plasma derivatives;
Preparation of labile blood components;
Inventory management;
Hematopoietic progenitor cell collection and storage;
Collection and storage of tissues;
Quality management and good manufacturing practice;
Automation and information technology.
3) Transfusion Medicine and New Therapies:
Transfusion thresholds and audits;
Haemovigilance;
Clinical trials regarding appropriate haemotherapy;
Non-infectious adverse affects of transfusion;
Therapeutic apheresis;
Support of transplant patients;
Gene therapy and immunotherapy.
4) Immunohaematology and Immunogenetics:
Autoimmunity in haematology;
Alloimmunity of blood;
Pre-transfusion testing;
Immunodiagnostics;
Immunobiology;
Complement in immunohaematology;
Blood typing reagents;
Genetic markers of blood cells and serum proteins: polymorphisms and function;
Genetic markers and disease;
Parentage testing and forensic immunohaematology.
5) Cellular Therapy:
Cell-based therapies;
Stem cell sources;
Stem cell processing and storage;
Stem cell products;
Stem cell plasticity;
Regenerative medicine with cells;
Cellular immunotherapy;
Molecular therapy;
Gene therapy.