Department of Immunology, Complutense University, Madrid, Spain; Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain.
Research Institute Hospital Universitario La Paz (IdiPaz), Madrid, Spain; Ciber de Enfermedades Raras, Madrid, Spain.
Mol Immunol. 2018 Oct;102:42-57. doi: 10.1016/j.molimm.2018.06.011. Epub 2018 Jun 18.
Genetic variability in the complement system and its association with disease has been known for more than 50 years, but only during the last decade have we begun to understand how this complement genetic variability contributes to the development of diseases. A number of reports have described important genotype-phenotype correlations that associate particular diseases with genetic variants altering specific aspects of the activation and regulation of the complement system. The detailed functional characterization of some of these genetic variants provided key insights into the pathogenic mechanisms underlying these pathologies, which is facilitating the design of specific anti-complement therapies. Importantly, these analyses have sometimes revealed unknown features of the complement proteins. As a whole, these advances have delineated the functional implications of genetic variability in the complement system, which supports the implementation of a precision medicine approach based on the complement genetic makeup of the patients. Here we provide an overview of rare complement variants and common polymorphisms associated with disease and discuss what we have learned from them.
遗传变异在补体系统及其与疾病的关联已经有超过 50 年的历史，但直到过去十年，我们才开始了解这种补体遗传变异性如何导致疾病的发展。许多报告描述了重要的基因型-表型相关性，将特定疾病与改变补体系统激活和调节特定方面的遗传变异相关联。对其中一些遗传变异的详细功能特征分析提供了对这些病理生理学潜在致病机制的关键见解，从而促进了特异性抗补体治疗的设计。重要的是，这些分析有时揭示了补体蛋白的未知特征。总的来说，这些进展阐明了补体系统遗传变异性的功能意义，支持了基于患者补体遗传构成的精准医疗方法的实施。在这里，我们提供了与疾病相关的罕见补体变异和常见多态性的概述，并讨论了我们从这些变异中得到的启示。
