小柯机器人

英国伦敦大学学院Judith Breuer团队报道儿童不明原因的急性肝炎的基因组学调查。相关论文于2023年3月30日在线发表在《自然》杂志上。

研究人员报告了对38个病例、66个年龄匹配的免疫功能正常的对照组和21个免疫功能低下的参照组的调查，并采用了基因组、转录组、蛋白质组和免疫组织化学方法。研究人员在27/28个病例的肝脏、血液、血浆或粪便中检测到高水平的腺相关病毒2（AAV2）DNA。分别在23/31和16/23的测试病例中，研究人员发现腺病毒（HAdV）和人类疱疹病毒6B（HHV-6B）的水平很低。相反，在患有HAdV的对照组儿童的血液或肝脏中很少检测到低滴度的AAV2，即使在严重免疫抑制的情况下也是如此。AAV2、HAdV和HHV-6的系统发育排除了病例中出现的新毒株。移植肝脏的组织学分析显示T细胞和B系细胞富集。

对病例和健康对照组的肝脏组织进行蛋白质组学比较，研究人员发现2类HLA、免疫球蛋白可变区和补体蛋白的表达增加。肝脏中没有检测到HAdV和AAV2蛋白。相反，研究人员发现AAV2 DNA复合物反映了HAdV和HHV-6B介导的复制。研究人员认为，高水平的异常AAV2复制产物在HAdV和严重的HHV-6B的帮助下，可能引发了遗传和免疫易感儿童的免疫介导的肝脏疾病。

据了解，自苏格兰首次发现儿童肝炎以来，全世界已报道了1000多例不明原因的儿童肝炎，包括英国的278例。

附：英文原文

Title: Genomic investigations of unexplained acute hepatitis in children

Author: Morfopoulou, Sofia, Buddle, Sarah, Montaguth, Oscar Enrique Torres, Atkinson, Laura, Guerra-Assuno, Jos Afonso, Marjaneh, Mahdi Moradi, Chiozzi, Riccardo Zenezini, Storey, Nathaniel, Campos, Luis, Hutchinson, J. Ciaran, Counsell, John R., Pollara, Gabriele, Roy, Sunando, Venturini, Cristina, Antinao Diaz, Juan F., Siam, Alaa, Tappouni, Luke J., Asgarian, Zeinab, Ng, Joanne, Hanlon, Killian S., Lennon, Alexander, McArdle, Andrew, Czap, Agata, Rosenheim, Joshua, Andrade, Catarina, Anderson, Glenn, Lee, Jack C. D., Williams, Rachel, Williams, Charlotte A., Tutill, Helena, Bayzid, Nadua, Bernal, Luz Marina Martin, Macpherson, Hannah, Montgomery, Kylie-Ann, Moore, Catherine, Templeton, Kate, Neill, Claire, Holden, Matt, Gunson, Rory, Shepherd, Samantha J., Shah, Priyen, Cooray, Samantha, Voice, Marie, Steele, Michael, Fink, Colin, Whittaker, Thomas E., Santilli, Giorgia, Gissen, Paul, Kaufer, Benedikt B., Reich, Jana, Andreani, Julien, Simmonds, Peter, Alrabiah, Dimah K., Hereza, Sergi Castellano, Chikowore, Primrose, Odam, Miranda, Rampling, Tommy, Houlihan, Catherine, Hoschler, Katja, Talts, Tiina, Celma, Cristina, Gonzalez, Suam, Gallagher, Eileen, Simmons, Ruth, Watson, Conall, Mandal, Sema, Zambon, Maria, Chand, Meera, Hatcher, James

Issue&Volume: 2023-03-30

Abstract: Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1. Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells. Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

DOI: 10.1038/s41586-023-06003-w

Source: https://www.nature.com/articles/s41586-023-06003-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html