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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Indeterminate pediatric acute liver failure is uniquely characterized by a CD103 + + CD8 + + T‐cell infiltrate
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Indeterminate pediatric acute liver failure is uniquely characterized by a CD103 + + CD8 + + T‐cell infiltrate

机译:不确定的儿科急性肝功能衰竭具有CD103 + + CD8 + + T细胞浸润的唯一特征

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The cause of pediatric acute liver failure (PALF) is unknown in up to 40% of cases. Evidence suggests that aberrant immune system activation may play a role. We hypothesized that indeterminate PALF cases would exhibit a unique pattern of hepatic inflammation. This was a retrospective and prospective study of PALF cases due to indeterminate (iPALF), autoimmune hepatitis, or known diagnosis (dPALF) etiology. Liver tissue sections were stained with immunohistochemical markers for cytotoxic T‐cells (cluster of differentiation 8 [CD8]), perforin, and tissue resident memory T‐cells (CD103) and scored as minimal, moderate, or dense. Lymphocytes were isolated from liver tissue for T‐cell receptor beta sequencing and flow‐cytometric studies. Thirty‐three iPALF, 9 autoimmune hepatitis, and 14 dPALF cases were included. Dense hepatic infiltrates of CD8 + T‐cells were found in 27 (82%) iPALF cases compared to 1 (7%) dPALF case ( P 0.0001). Perforin staining was dense or moderate in 19 (73%) of 26 iPALF cases compared to minimal in all 7 dPALF cases ( P = 0.004); 16 (62%) of 26 iPALF cases had dense CD103 staining compared to none of the 6 dPALF cases ( P = 0.001). T‐cell receptor beta sequencing of iPALF cases demonstrated increased clonality compared to dPALF and control cases. Flow cytometry and immunohistochemistry revealed that iPALF intrahepatic leukocytes were predominantly tissue resident memory CD8 + T‐cells. Conclusion : Indeterminate PALF is characterized by a dense CD8 + T‐cell hepatic infiltrate consistent with expansion of a tissue resident memory T‐cell phenotype; CD8 + T‐cells are a biomarker of immune dysregulation in iPALF and may be used to better identify and define this group. (H epatology 2018).
机译:儿科急性肝功能衰竭(PALF)的原因在40%的情况下未知。证据表明,异常免疫系统激活可能发挥作用。我们假设不确定的PALF病例将表现出独特的肝脏炎症模式。这是对PALF病例的回顾性和前瞻性研究,由于不确定(IPALF),自身免疫性肝炎或已知的诊断(DPALF)病因。肝组织切片对细胞毒性T细胞的免疫组织化学标记染色(分化8 [CD8]),穿孔素和组织驻留记忆T细胞(CD103),并均可均匀,中等或致密。从肝组织中分离出淋巴细胞,用于T细胞受体β测序和流式细胞研究。包括三十三个IPALF,9例自身免疫性肝炎和14例DPALF病例。与1(7%)DPALF案例相比,在27(82%)IPALF病例中发现了CD8 + T细胞的致密肝渗透,与1(7%)DPALF案例(P <0.0001)相比。与所有7例DPALF病例中的最小值相比,穿孔素染色于19(73%)的26例(73%)(73%)(p = 0.004); 16(62%)26例IPALF病例浓密,与6例DPALF病例中的任何一株相比染色(P = 0.001)。与DPALF和对照病例相比,IPALF病例的T细胞受体β测序表明克隆性增加。流式细胞术和免疫组织化学显示,IPALF肝内白细胞主要是组织驻留记忆CD8 + T细胞。结论:不确定的PALF的特征在于致密的CD8 + T细胞肝渗透,与组织常规记忆T细胞表型的膨胀一致; CD8 + T细胞是IPALF中免疫失调的生物标志物,可用于更好地识别和定义该组。 (2018年Hopatology)。

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