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MHC II deficient infant identified by newborn screening program for SCID

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Abstract

Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), using the TREC-based assay, have enabled early diagnosis, prompt treatment, and eventually changed the natural history of affected infants. Nevertheless, it was believed that some affected infants with residual T cell, such as patients with MHC II deficiency, will be misdiagnosed by this assay. A full immune workup and genetic analysis using direct Sanger sequencing and whole exome sequencing have been performed to a patient that was identified by the Israeli NBS program for SCID. The patient was found to have severe CD4 lymphopenia with an inverted CD4/CD8 ratio, low TREC levels in peripheral blood, abnormal response to mitogen stimulation, and a skewed T cell receptor repertoire. HLA-DR expression on peripheral blood lymphocytes was undetectable suggesting a diagnosis of MHC II deficiency. Direct sequencing of the RFX5 gene revealed a stop codon change (p. R239X, c. C715T), which could cause the patient’s immune phenotype. His parents were found to be heterozygote carriers for the mutation. Whole exome sequencing could not identify other potential mutations to explain his immunodeficiency. The patient underwent successful conditioned hematopoietic stem cell transplantation from healthy matched unrelated donor and is currently well and alive with full chimerism. Infants with MHC class II deficiency can potentially be identified by the TREC-based assay NBS for SCID. Therefore, MHC II molecules (e.g., HLA-DR) measurement should be part of the confirmatory immune-phenotyping for patients with positive screening results. This will make the diagnosis of such patients straightforward.

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Abbreviations

HSCT:

Hematopoietic stem cell transplantation

MHC:

Major histocompatibility complex

NBS:

Newborn screening

SCID:

Severe combined immunodeficiency

TCR:

T cell receptor

TRECs:

T cell receptor excision circles

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Authors and Affiliations

  1. Allergy and Immunology Unit, Felsenstein Medical Research Center, Kipper Institute of Immunology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

    Nufar Marcus

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Nufar Marcus, Jerry Stein & Raz Somech

  3. Pediatric Department A, Pediatric Immunology Service, Jeffrey Modell Foundation Center, 52621, Tel Hashomer, Israel

    Tali Stauber, Atar Lev, Amos J. Simon & Raz Somech

  4. Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, 52621, Tel Hashomer, Israel

    Tali Stauber, Atar Lev, Amos J. Simon & Raz Somech

  5. Department for Hemato-Oncology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

    Jerry Stein

  6. Pediatric Immunology Clinic, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Arnon Broides

  7. Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany

    Ido Somekh

  8. The National Center for Newborn Screening, Ministry of Health, 52621, Tel HaShomer, Israel

    Shlomo Almashanu

  9. The National Lab for Confirming Primary Immunodeficiency in Newborn Screening Center for Newborn Screening, Ministry of Health, Tel HaShomer, Israel

    Raz Somech

Authors
  1. Nufar Marcus
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  2. Tali Stauber
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  3. Atar Lev
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  4. Amos J. Simon
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  5. Jerry Stein
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  6. Arnon Broides
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  7. Ido Somekh
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  8. Shlomo Almashanu
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  9. Raz Somech
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Corresponding author

Correspondence to Raz Somech.

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Marcus, N., Stauber, T., Lev, A. et al. MHC II deficient infant identified by newborn screening program for SCID. Immunol Res 66, 537–542 (2018). https://doi.org/10.1007/s12026-018-9019-2

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  • DOI: https://doi.org/10.1007/s12026-018-9019-2

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