Lenardo Michael, Lo Bernice, Lucas Carrie L
Molecular Development of the Immune System Section, Laboratory of Immunology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; email:
Annu Rev Immunol. 2016 May 20;34:121-49. doi: 10.1146/annurev-immunol-041015-055620. Epub 2015 Dec 23.
Genomic DNA sequencing technologies have been one of the great advances of the 21st century, having decreased in cost by seven orders of magnitude and opening up new fields of investigation throughout research and clinical medicine. Genomics coupled with biochemical investigation has allowed the molecular definition of a growing number of new genetic diseases that reveal new concepts of immune regulation. Also, defining the genetic pathogenesis of these diseases has led to improved diagnosis, prognosis, genetic counseling, and, most importantly, new therapies. We highlight the investigational journey from patient phenotype to treatment using the newly defined XMEN disease, caused by the genetic loss of the MAGT1 magnesium transporter, as an example. This disease illustrates how genomics yields new fundamental immunoregulatory insights as well as how research genomics is integrated into clinical immunology. At the end, we discuss two other recently described diseases, CHAI/LATAIE (CTLA-4 deficiency) and PASLI (PI3K dysregulation), as additional examples of the journey from unknown immunological diseases to new precision medicine treatments using genomics.
基因组DNA测序技术是21世纪的重大进展之一，其成本已降低了七个数量级，并在整个研究和临床医学领域开辟了新的研究领域。基因组学与生化研究相结合，使得越来越多新的遗传疾病得到分子层面的定义，揭示了免疫调节的新概念。此外，明确这些疾病的遗传发病机制有助于改善诊断、预后、遗传咨询，最重要的是带来新的治疗方法。我们以新定义的XMEN病为例，突出从患者表型到治疗的研究历程，XMEN病是由MAGT1镁转运蛋白的基因缺失引起的。这种疾病说明了基因组学如何产生新的基础免疫调节见解，以及研究基因组学如何融入临床免疫学。最后，我们讨论另外两种最近描述的疾病，CHAI/LATAIE（CTLA-4缺陷）和PASLI（PI3K失调），作为从未知免疫疾病到使用基因组学进行新的精准医学治疗这一历程的其他示例。
