Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.
Effector memory CD8 T-cells as a novel peripheral blood biomarker for activated T-cell pediatric acute liver failure.
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DOI：
10.1371/journal.pone.0286394
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
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小儿急性肝衰竭（PALF）的一种独特的表型已被确定，标记为活化t细胞肝炎。这些患者先前被纳入不确定组，有系统性免疫激活的证据，肝活检标本中CD8+ t细胞密集浸润。我们的目的是评估与不明原因的活化t细胞肝炎相比，PALF患者外周血t细胞表型。在2017-2020年期间前瞻性纳入1-17岁病因不明的PALF患者。在未知组中，如果患者进行肝活检伴有密集或中度CD8染色，且可溶性白细胞介素-2受体水平升高，则将其分类为活动性t细胞肝炎，或者如果他们不符合这些标准，则将其分类为不确定型。采集全血进行流式细胞术和t细胞表型分析。4例活化t细胞肝炎患者和4例不确定PALF患者入组。与不确定的PALF患者相比，活化t细胞肝炎患者的效应记忆（TEM）表型CD8 t细胞比例显著更高(中位数66.8% （IQR 57.4-68.7) vs 19.1% (IQR 13.4-25.2), P = 0.03）。此外，与不确定的PALF患者相比，活化t细胞肝炎患者的CD8+ TEM细胞明显更有可能呈CD103阳性，CD103是组织常驻记忆t细胞的标志(中位数12.4% （IQR 9.5-14.7) vs 4.7% (IQR 4.5-5.3), P = 0.03）。我们发现活化t细胞肝炎患者可以通过外周血效应记忆CD8+ CD103+ t细胞百分比增加的独特模式来识别。这些发现将指导未来的研究，探索这些患者的t细胞表型，以及他们是否可能对定向免疫抑制疗法有反应。
A distinct phenotype of pediatric acute liver failure (PALF) has been identified, labeled activated T-cell hepatitis. These patients, previously included within the indeterminate group, have evidence of systemic immune activation and liver biopsy specimens with dense infiltration of CD8+ T-cells. We aimed to evaluate the peripheral blood T-cell phenotype in PALF patients with activated T-cell hepatitis compared to indeterminate cause. PALF patients with unknown etiology age 1–17 years were prospectively enrolled between 2017–2020. Within the unknown group, patients were classified as either activated T-cell hepatitis if they had a liver biopsy with dense or moderate CD8 staining and an elevated soluble interleukin-2 receptor level, or they were classified as indeterminate if they did not meet these criteria. Whole blood was collected for flow cytometry and T-cell phenotyping. Four patients with activated T-cell hepatitis and 4 patients with indeterminate PALF were enrolled. Activated T-cell hepatitis patients had significantly greater percentage of CD8 T-cells that were effector memory (TEM) phenotype compared to indeterminate PALF patients (median 66.8% (IQR 57.4–68.7) vs 19.1% (IQR 13.4–25.2), P = 0.03). In addition, CD8+ TEM cells in activated T-cell hepatitis patients were significantly more likely to be CD103 positive, a marker of tissue resident memory T-cells, compared to indeterminate PALF patients (median 12.4% (IQR 9.5–14.7) vs 4.7% (IQR 4.5–5.3), P = 0.03). We found patients with activated T-cell hepatitis can be identified by the unique pattern of increased percentage of peripheral blood effector memory CD8+ CD103+ T-cells. These findings will guide future studies exploring the T-cell phenotype for these patients and whether they may respond to directed immunosuppressive therapies.
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