T cell clonal expansion and STAT3 mutations: a characteristic feature of acquired chronic T cell-mediated pure red cell aplasia
T cell clonal expansion and STAT3 mutations: a characteristic feature of acquired chronic T cell-mediated pure red cell aplasia
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DOI：
10.1007/s12185-022-03310-2
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发表时间：
2022-03-11
影响因子：
2.1
通讯作者：
Ishida, Fumihiro
中科院分区：
文献类型：
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作者：
Kawakami, Fumihiro;Kawakami, Toru;Ishida, Fumihiro
获得性慢性纯红细胞再生障碍性贫血（PRCA）是一种特发性疾病，或与其他疾病相关，包括T细胞大颗粒淋巴细胞白血病（T-LGLL）和胸腺瘤。T细胞失调被认为是PRCA的主要发病机制，但T细胞异常的遗传-表型关联在很大程度上尚不清楚。我们评估了90例获得性PRCA患者的扩展队列，其中包括26例特发性PRCA，36例T-LGLL相关PRCA和15例胸腺瘤相关PRCA，用于T细胞免疫表型，克隆性和STAT 3突变。在37.5%的特发性PRCA患者、66.7%的T-LGLL相关PRCA患者和25%的胸腺瘤相关PRCA患者中检测到CD 8（+）T细胞的TCR库偏斜，并且对V β 1的限制最为突出（41%）。TCR β或γ链的克隆性与STAT 3突变状态具有统计学相关性（P = 0.0398），并且在所有三种亚型中均检测到。环孢菌素A的总应答率为73.9%，亚型和STAT 3突变状态之间无显著差异。T细胞失调，如TCR库偏斜与主要V β 1的使用，克隆性和STAT 3突变，经常发现在亚型，它们之间的密切联系表明，这些T细胞紊乱反映了这些PRCA亚型之间的共同病理生理机制。
Acquired chronic pure red cell aplasia (PRCA) develops idiopathically or in association with other medical conditions, including T cell large granular lymphocytic leukemia (T-LGLL) and thymoma. T cell dysregulation is considered a cardinal pathogenesis of PRCA, but genetic-phenotypic associations in T cell abnormalities are largely unclear. We evaluated an extended cohort of 90 patients with acquired PRCA, including 26 with idiopathic, 36 with T-LGLL-associated and 15 with thymoma-associated PRCA, for their T cell immuno-phenotypes, clonalities and STAT3 mutations. TCR repertoire skewing of CD8(+) T cells was detected in 37.5% of idiopathic, 66.7% of T-LGLL-associated and 25% of thymoma-associated PRCA patients, and restriction to V beta 1 was most prominent (41%). Clonalities of TCR beta or gamma chain and STAT3 mutational status were statistically associated (P = 0.0398), and they were detected in all three subtypes. The overall response rate to cyclosporin A was 73.9%, without significant difference by subtypes nor STAT3 mutational status. The T cell dysregulations, such as TCR repertoire skewing with predominant V beta 1 usage, clonality and STAT3 mutations, were frequently found across the subtypes, and the close associations between them suggest that these T cell derangements reflect a common pathophysiological mechanism among these PRCA subtypes.