文章：

双重T细胞受体β链恒定区(TRBC1/TRBC2)染色用于流式细胞术鉴定T细胞肿瘤

Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry

原文发布日期：2024-02-29

DOI: 10.1038/s41408-024-01002-0

类型: Article

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英文摘要：

The diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+ and CD8+ T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p < 0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 24 clinical specimens (15%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies.
 

摘要翻译： 

白血病性T细胞恶性肿瘤的诊断往往具有挑战性，其原因在于其与反应性T细胞特征存在重叠，且当前可用的T细胞克隆性检测方法存在局限。近期研发的治疗性抗体可特异性识别互斥的T细胞受体恒定β链（TRBC）1和TRBC2异构体，这为在T细胞肿瘤流式细胞分析中通过评估TRBC限制性作为克隆性替代指标提供了独特机遇。为验证该方法的诊断效用，我们研究了164例临床标本（含60例T细胞肿瘤及104例非肿瘤样本），并纳入39例健康供者血液样本。采用与常规检测B细胞克隆性的κ/λ免疫球蛋白轻链评估相似的方式，在综合性T细胞检测组合中分析了TRBC1和TRBC2的双重表达。所有健康供者的总T细胞、CD4+及CD8+ T细胞均呈现多型性TRBC表达；经胞内染色证实良性T细胞前体亦具此特征。除8例（13%）缺乏TRBC表达的病例外，所有肿瘤性T细胞均显示TRBC限制性表达。在17例无T细胞恶性肿瘤的样本（13%）中发现了意义未明的T细胞克隆，其细胞比例显著低于肿瘤性克隆（中位数：淋巴细胞占比4.7%对69%，p<0.0001）。单一TRBC1染色在24例临床标本（15%）中产生了假性TRBC1弱表达亚群，而双重TRBC1/2染色可完全消除此现象。通过流式细胞术评估TRBC限制性，为检测克隆性T细胞及精准判定T细胞恶性肿瘤表达的可靶向TRBC异构体提供了快速诊断方法。

原文链接：

Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry