Identification of an infant with severe combined immunodeficiency by newborn screening

Hale, Jaime E.; Bonilla, Francisco A.; Pai, Sung-Yun; Gerstel-Thompson, Jacalyn L.; Notarangelo, Luigi D.; Eaton, Roger B.; Comeau, Anne Marie

doi:10.1016/j.jaci.2010.08.043

Cited by 45 publications

(33 citation statements)

References 6 publications

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“…While infants with SCID and primary and secondary T cell defects can now be readily identified, referral centers are also identifying infants with idiopathic TCL the unexpected observation that infants with idiopathic TCL are also being identified [1,3,5] prompted longer term follow-up of such infants in this report. The true incidence of this is not clear, but the overall denominator reported for New York State, was 30 lymphopenic infants in 2 years, with 485,912 infants screened in this interval [8].…”

Section: Discussionmentioning

confidence: 99%

“…The method of evaluating T-cell receptor excision circles (TRECs) to universally screen infants for a profound deficiency in T cells in the newborn period was established in Wisconsin and Massachusetts in 2009, based on methodology developed by Puck [1–5]. This practice has now been extended to the majority of states and the success of this approach in identifying infants with severe combined immunodeficiency (SCID) and other forms of severe T cell impairment, has been proven [3,4,6–9].…”

Section: Introductionmentioning

confidence: 99%

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Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Albin-Leeds

Ochoa

Mehta

et al. 2017

Clinical Immunology

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Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. We performed a retrospective review of clinical and laboratory studies for 26 infants collected from 7 New York State referral centers from 2010 to 2016 with low TRECs (mean, 70 copies/μl) and subnormal CD3 counts (mean, 1150/cubic mm). Over time absolute CD3 counts increased in 17 and decreased in 9; 22 (85%) have done well clinically regardless of absolute T cell values. Additional infants with TCL will continue to be identified in newborn screening panels. While most patients seem to do well clinically, parameters for diagnosis and monitoring have yet to be formalized, and additional information needs to be collected, causes and outcomes reported.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Albin-Leeds

Ochoa

Mehta

et al. 2017

Clinical Immunology

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“…T-cell receptor excision circle (TREC) levels were determined by using real-time quantitative PCR of genomic DNA with RNAse P as the control gene 32,33 and newborn screening dried blood spot specimens retrieved with informed consent (patient 1) or in the course of universal pilot screening (patient 2). Determination of TREC levels in patient 3 was performed at age 23 months by using quantitative PCR of genomic DNA from PBMCs with albumin as the internal control of genomic DNA amplification.…”

Section: Methodsmentioning

confidence: 99%

Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment

Cattaneo¹,

Recher²,

Masneri³

et al. 2013

Journal of Allergy and Clinical Immunology

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Background: Mutations in Janus kinase 3 (JAK3) are a cause of severe combined immunodeficiency, but hypomorphic JAK3 defects can result in a milder clinical phenotype, with residual development and function of autologous T cells. Maternal T-cell engraftment is a common finding in infants with severe combined immunodeficiency but is not typically observed in patients with residual T-cell development. Objective: We sought to study in detail the molecular, cellular, and humoral immune phenotype and function of 3 patients with hypomorphic JAK3 mutations. Methods: We analyzed the distribution and function of T and B lymphocytes in 3 patients and studied the in vitro and in vivo responses of maternal T lymphocytes in 1 patient with maternal T-cell engraftment and residual production of autologous T lymphocytes. Results: B cells were present in normal numbers but with abnormal distribution of marginal zone–like and memory B cells. B-cell differentiation to plasmablasts in vitro in response to CD40 ligand and IL-21 was abolished. In 2 patients the T-cell repertoire was moderately restricted. Surprisingly, 1 patient showed coexistence of maternal and autologous T lymphocytes. By using an mAb recognizing the maternal noninherited HLA-A2 antigen, we found that autologous cells progressively accumulated in vivo but did not compete with maternal cells in vitro. Conclusion: The study of 3 patients with hypomorphic JAK3 mutations suggests that terminal B-cell maturation/ differentiation requires intact JAK3 function, even if partially functioning T lymphocytes are present. Maternal T-cell engraftment can occur in patients with JAK3 mutations despite the presence of autologous T cells.

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“…In Massachusetts, 100,597 infants were screened for SCID in a pilot program. (29) Of these, 78 infants needed additional testing. One infant was identified as having SCID and successfully underwent a hematopoietic stem cell transplant before becoming symptomatic.…”

Section: Current Status Of Severe Combined Immunodeficiency Screeningmentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency

Randolph¹,

Routes²,

Verbsky³

2013

NeoReviews

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Verbsky have disclosed no financial relationships relevant to this article. Dr Routes has disclosed that he has a research grant from Baxter US, in Deerfield, IL. This commentary does contain a discussion of an unapproved/ investigative use of a commercial product/ device. Educational GapAs screening programs for severe combined immunodeficiency increase in prevalence, there may be new implications for clinical practice, including an awareness of the variety of genetic causes, the presentation, and the treatment of this disorder. AbstractSevere combined immunodeficiency (SCID) is a rare disorder that is lethal in childhood if not diagnosed and treated properly. Recently, a number of states have begun neonatal screening programs for SCID to facilitate diagnosis and improve outcomes. Here we review the pathogenesis and treatment of SCID. We also review the rationale for statewide screening programs, the molecular basis for the screening test, and discuss the experience to date of statewide screening in Wisconsin, the first state to implement such a program.Objectives After completing this article, readers should be able to:1. List steps of T-cell development at which various molecular defects can lead to severe combined immunodeficiency (SCID) or severe T-cell lymphopenia. 2. Describe the common presentations of SCID, particularly in the newborn period. 3. Describe therapies for SCID and the rationale for initiating therapy as soon as possible. 4. Describe the molecular basis for newborn SCID screening.

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Identification of an infant with severe combined immunodeficiency by newborn screening

Cited by 45 publications

References 6 publications

Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Idiopathic T cell lymphopenia identified in New York State Newborn Screening

Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment

Newborn Screening for Severe Combined Immunodeficiency

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