Identification of Severe Combined Immunodeficiency by T-Cell Receptor Excision Circles Quantification Using Neonatal Guthrie Cards

Morinishi, Yoichi; Imai, Kohsuke; Nakagawa, Noriko; Sato, Hiroki; Horiuchi, Katsuyuki; Ohtsuka, Yoshitoshi; Kaneda, Yumi; Taga, Takashi; Hashimoto, Hiroaki; Miyaji, Ryosuke; Endo, Makoto; Oh‐ishi, Tsutomu; Kamachi, Yusuke; Akahane, Koshi; Kobayashi, Chie; Tsuchida, Masahiro; Morio, Tomohiro; Sasahara, Yoji; Kumaki, Satoru; Ishigaki, Keiko; Yoshida, Makoto; Urabe, Tomonari; Kobayashi, N.; Okimoto, Yuri; Reichenbach, Janine; Hashii, Yoshiko; Tsuji, Yoshitaka; Kogawa, Kazuhiro; Yamaguchi, Seiji; Kanegane, Hirokazu; Miyawaki, Toshio; Yamada, Masafumi; Ariga, Tadashi; Nonoyama, Shigeaki

doi:10.1016/j.jpeds.2009.05.026

Cited by 106 publications

(61 citation statements)

References 19 publications

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“…Measurement of TREC and KREC levels TREC, sjKREC and cjKREC levels were measured by real-time PCR as described previously [15][16][17][18][19] at 1, 3 and 6 months, and yearly after HCT. RNase P was used as an internal control.…”

Section: Introductionmentioning

confidence: 99%

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Nakatani

Imai

Shigeno

et al. 2014

Bone Marrow Transplant

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Hematopoietic cell transplantation (HCT) is used for treatment of hematopoietic diseases. Assessment of T-and B-cell reconstitution after HCT is crucial because poor immune recovery has a major effect on the clinical course. In this study, we retrospectively analyzed T-cell receptor excision circles (TRECs) as well as signal and coding joint kappa-deleting recombination excision circles (sjKRECs and cjKRECs, respectively) as markers of newly produced lymphocytes in 133 patients (56 primary immunodeficient and 77 malignant cases, median (range): 12 (0-62) years old). We analyzed the kinetics of TREC and KREC recovery and determined the factors that contributed to better immune recovery. KRECs became positive earlier than TRECs and increased thereafter. Younger recipient age had a favorable effect on recovery of sjKRECs and cjKRECs. Compared with BM and peripheral blood, our data suggested that cord blood (CB) provided rapid B-cell recovery. CB also provided better B-cell neogenesis in adult HCT recipients. Chronic GVHD was associated with low TRECs, but not increased sjKRECs/cjKRECs. Finally, positive sjKRECs 1 month after HCT were associated with fewer infectious episodes. Monitoring of TRECs and KRECs may serve as a useful tool for assessment of immune reconstitution post HCT.

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Section: Introductionmentioning

confidence: 99%

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Nakatani

Imai

Shigeno

et al. 2014

Bone Marrow Transplant

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“…Following the pilot program in Wisconsin, the TREC assay was subsequently shown to successfully detect various forms of SCID, regardless of the molecular cause [26]. Perhaps more importantly, the same study showed the presence of maternal T cells, or T cell from either leaky SCID or hypomorphic mutations did not affect the outcome of the assay.…”

Section: Improvements In the Trec Assay Lead To Nbs For Scidmentioning

confidence: 98%

“…For subjects in whom peripheral T cells were found but TRECS were undetectable, fluorescent in-situ hybridization (FISH) analysis showed the cells were contributed from the mother. Because the δRec/ψJα TREC is found primarily in naïve T-cells and not memory cells, maternally engrafted cells will not contribute to the TREC count in infant samples, nor will residual memory cells found in Omenn Syndrome, RAG1 deficiency, or ADA deficiency for the same reason [26]. Other conditions with absent or low TRECs that would be detected by this assay include syndromic conditions affecting T cell development (e.g., CHARGE syndrome, Jacobsen syndrome, RAC2 defect, Ataxia telangelactasia, Trisomy 21 and 18), secondary T cell lymphopenias (e.g., Chylothorax, gastrointestinal atresia, hypoplastic left heart syndrome, neonatal leukemia, congenital anomalies) and prematurity [2].…”

Section: Improvements In the Trec Assay Lead To Nbs For Scidmentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency-A History of the TREC Assay

Bausch-Jurken

Verbsky

Routes

2017

IJNS

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Abstract:Infants born with T cell lymphopenias, especially severe combined immunodeficiency (SCID) are at risk for serious, often fatal infections without intervention within the first year or two of life. The majority of these disorders can be detected through the use of the T cell recombination excision circle assay (TREC assay.) The TREC assay detects the presence of non-replicating, episomal DNA that is formed during T cell development. This assay initially developed to measure thymic output during aging and HIV infection, has undergone modifications for the purpose of newborn screening (NBS) for SCID. To meet the requirements for inclusion on NBS panels, the assay needed to utilize blood from dried blood spots on NBS cards, and be both sensitive and specific, avoiding the costs of false positives. Currently, the assay relies upon real time, quantitative PCR (RT-qPCR) to detect TRECs in punches taken from dried blood spots. This review seeks to highlight some of the early work leading up to the initial implementation of the TREC assay for SCID detection, and the subsequent revisions made to optimize the assay.

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“…Newborn screening (NBS) for a number of T and B lymphocyte deficiencies is now available and has already been implemented in a few countries [52,53] . NBS is performed using real-time polymerase chain reaction on DNA extracted from blood collected on NBS cards.…”

Section: Future Perspectives: Neonatal Screening For Pidsmentioning

confidence: 99%

Consanguinity and Primary Immunodeficiencies

et al. 2014

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Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families.

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Identification of Severe Combined Immunodeficiency by T-Cell Receptor Excision Circles Quantification Using Neonatal Guthrie Cards

Cited by 106 publications

References 19 publications

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

Newborn Screening for Severe Combined Immunodeficiency-A History of the TREC Assay

Consanguinity and Primary Immunodeficiencies

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