Expression of HLA and Autoimmune Pathway Genes in Liver Biopsies of Young Subjects With Autoimmune Hepatitis Type 1.
Expression of HLA and Autoimmune Pathway Genes in Liver Biopsies of Young Subjects With Autoimmune Hepatitis Type 1.
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DOI：
10.1097/mpg.0000000000003538
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发表时间：
2022-09-01
影响因子：
2.9
通讯作者：
Yolken, Robert H.
中科院分区：
文献类型：
--
作者：
Shin, Emilia;Schwarz, Kathleen B.;Jones-Brando, Lorraine, V;Florea, Liliana D.;Sabunciyan, Sarven;Wood, Laura Delong;Yolken, Robert H.
为了验证年轻受试者中自身免疫性肝炎（AIH I型）是由于患者和对照组中对病毒触发物应答的促炎基因的遗传差异所致的假设。比较AIH I型（n = 24，年龄9-30岁）患者（以下称为AIH组）和对照组（n = 21，年龄4-25岁）之间的肝内基因表达。对从福尔马林固定石蜡包埋（FFPE）肝活检样品中提取的总RNA制备的互补DNA（cDNA）文库进行RNA测序。对基因表达水平进行定量，并对差异表达的基因进行功能分析。使用数据库京都基因和基因组百科全书（KEGG）和PANTHER进行途径分析。将剩余的序列映射到RefSeq病毒基因组的完整集合。差异基因分析确定了181个显著差异表达的基因（136个在AIH组中上调）。自身免疫途径基因如在B细胞调节和成熟中重要的CD 19和CD 20以及与T细胞相关的CD 8和LY 9在我们的AIH组中上调。AIH发病机制中涉及的基因包括CXCL 10，其被认为与AIH严重程度和进展相关，补体基因（C1 QA，C1 QB和C1 QC）和人类白细胞抗原（HLA）基因（HLA-DRB 1，HLA-B，HLA-C）在AIH组的样本中上调。无偏倚的下一代测序和AIH组的差异基因表达分析不仅为B细胞在AIH发病机制和治疗中的作用提供了支持，而且还引入了潜在的新治疗靶点：CXCL 10（抗CXCL 10）和几个补体系统相关基因。
To test the hypothesis that autoimmune hepatitis (AIH type I) in young subjects is due to genetic differences in proinflammatory genes responding to viral triggers in patients and controls. Intrahepatic gene expression was compared between AIH type I (n = 24, age 9–30 years) patients (hereafter referred to as the AIH group) and controls (n = 21, age 4–25 years). RNA sequencing was performed on complementary DNA (cDNA) libraries made from total RNA extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsy samples. Gene expression levels were quantified, and differentially expressed genes were functionally analyzed. Pathway analysis was performed using the databases Kyoto Encyclopedia of Genes and Genomes (KEGG) and PANTHER. The remaining sequences were mapped to the RefSeq complete set of viral genomes. Differential gene analysis identified 181 genes that were significantly differentially expressed (136 upregulated in the AIH group). Autoimmune pathway genes such as CD19 and CD20 which are important in B cell regulation and maturation as well as, CD8 and LY9, which are T-cell related, were upregulated in our AIH group. Genes implicated in AIH pathogenesis including CXCL10, which is thought to be associated with AIH severity and progression, complement genes (C1QA, C1QB, and C1QC), and human leucocyte antigen (HLA) genes (HLA-DRB1, HLA-DRA, HLA-B, and HLA-C) were upregulated in samples from the AIH group. Specific viral etiologies were not found. Unbiased next-generation sequencing and differential gene expression analysis of the AIH group has not only added support for the role of B cells in the pathogenesis and treatment of AIH but also has introduced potential new therapeutic targets: CXCL10 (anti-CXCL10) and several complement system–related genes.
影响因子：
2.8
作者：
Tu, Zhidan;Li, Qing;Chou, Hong-Shiue;Hsieh, Ching-Chuang;Meyerson, Howard;Peters, Marion G.;Bu, Hong;Fung, John J.;Qian, Shiguang;Lu, Lina;Lin, Feng
通讯作者：
Lin, Feng
影响因子：
3.7
作者：
Zhernakova DV;Kliver S;Cherkasov N;Tamazian G;Rotkevich M;Krasheninnikova K;Evsyukov I;Sidorov S;Dobrynin P;Yurchenko AA;Shimansky V;Shcherbakova IV;Glotov AS;Valle DL;Tang M;Shin E;Schwarz KB;O'Brien SJ
通讯作者：
O'Brien SJ