TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity.,Clinical & Experimental Immunology

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TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity.
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-06-26 , DOI: 10.1111/cei.13484
M Dasouki ₁ , A Jabr ₁ , G AlDakheel ₁ , F Elbadaoui ₁ , A M Alazami ₁ , B Al-Saud ₂ , R Arnaout ₂ , H Aldhekri ₂ , I Alotaibi ₂ , H Al-Mousa _{2,

3} , A Hawwari _{1,

4}

Affiliation

Primary immune deficiency (PID) disorders are clinically and molecularly heterogeneous diseases. T cell receptor excision circles (TRECs) and κ (kappa)‐deleting excision circles (KRECs) are markers of T and B cell development, respectively. They are useful tools to assess T and B cell function and immune reconstitution and have been used for newborn screening for severe combined immunodeficiency disease (SCID) and agammaglobulinemia, respectively. Their profiles in several genetically confirmed PIDs are still lacking. The objective of this study was to determine TREC and KREC genomic profiling among various molecularly confirmed PIDs. We used real‐time–quantitative polymerase chain reaction (RT–qPCR)‐based triplex analysis of TRECs, KRECs and β‐actin (ACTB) in whole blood genomic DNA isolated from 108 patients with molecularly confirmed PIDs. All agammaglobulinemia patients had low KREC counts. All SCIDs and Omenn syndrome patients secondary to mutations in RAG1, RAG2, DCLRE1C and NHEJ1 had low TREC and KREC counts. JAK3‐deficient patients had normal KREC and the TREC count was influenced by the type of mutation. Early‐onset ADA patients had low TREC and KREC counts. Four patients with zeta‐chain‐associated protein kinase 70 (ZAP70) had low TREC. All purine nucleoside phosphorylase (PNP) patients had low TREC. Combined immunodeficiency (CID) patients secondary to AK2, PTPRC, CD247, DCLREC1 and STAT1 had normal TREC and KREC counts. Most patients with ataxia–telangiectasia (AT) patients had low TREC and KREC, while most DOCK8‐deficient patients had low TRECs only. Two of five patients with Wiskott–Aldrich syndrome (WAS) had low TREC counts as well as one patient each with bare lymphocyte syndrome (BLS) and chronic granulomatous disease. All patients with Griscelli disease, Chediak–Higashi syndrome, hyper‐immunoglobulin (Ig)M syndrome and IFNGR2 had normal TREC and KREC counts. These data suggest that, in addition to classical SCID and agammaglobulinemia, TREC/KREC assay may identify ZAP70 patients and secondary target PIDs, including dedicator of cytokinesis 8 (DOCK8) deficiency, AT and some individuals with WAS and BLS.

中文翻译：

TREC 和 KREC 分析作为各种先天性免疫缺陷患者胸腺和骨髓输出的代表。

原发性免疫缺陷 (PID) 疾病是临床和分子异质性疾病。T细胞受体切除环（TRECs）和κ（kappa）缺失切除环（KRECs）分别是T细胞和B细胞发育的标志物。它们是评估 T 和 B 细胞功能以及免疫重建的有用工具，并已分别用于新生儿筛查严重联合免疫缺陷病 (SCID) 和丙种球蛋白血症。他们在几个经基因证实的 PID 中的资料仍然缺乏。本研究的目的是确定各种分子确认的 PID 之间的 TREC 和 KREC 基因组谱。我们使用基于实时定量聚合酶链反应 (RT-qPCR) 的三重分析对从 108 名分子确诊 PID 患者中分离的全血基因组 DNA 中的 TREC、KREC 和 β-肌动蛋白 (ACTB) 进行分析。所有无丙种球蛋白血症患者的 KREC 计数均较低。继发于基因突变的所有 SCID 和 Omenn 综合征患者RAG1、RAG2、DCLRE1C和NHEJ1 的TREC 和 KREC 计数较低。JAK3缺陷患者的 KREC 正常，TREC 计数受突变类型的影响。早发性 ADA 患者的 TREC 和 KREC 计数较低。四名 zeta 链相关蛋白激酶 70 (ZAP70) 患者的 TREC 较低。所有嘌呤核苷磷酸化酶 (PNP) 患者的 TREC 均较低。继发于AK2、PTPRC、CD247、DCLREC1和STAT1 的联合免疫缺陷 (CID) 患者具有正常的 TREC 和 KREC 计数。大多数共济失调-毛细血管扩张症 (AT) 患者的 TREC 和 KREC 较低，而大多数DOCK8‐缺陷患者仅具有低 TREC。5 名 Wiskott-Aldrich 综合征 (WAS) 患者中有 2 名 TREC 计数低，1 名患者分别患有裸淋巴细胞综合征 (BLS) 和慢性肉芽肿病。所有患有 Griscelli 病、Chediak-Higashi 综合征、高免疫球蛋白 (Ig)M 综合征和IFNGR2 的患者的 TREC 和 KREC 计数正常。这些数据表明，除了经典的 SCID 和无丙种球蛋白血症外，TREC/KREC 检测还可以识别 ZAP70 患者和次要目标 PID，包括胞质分裂 8 (DOCK8) 缺乏症的奉献者、AT 和一些 WAS 和 BLS 患者。

更新日期：2020-06-26

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