Immunologic Research

, Volume 66, Issue 4, pp 537–542 | Cite as

MHC II deficient infant identified by newborn screening program for SCID

  • Nufar Marcus
  • Tali Stauber
  • Atar Lev
  • Amos J. Simon
  • Jerry Stein
  • Arnon Broides
  • Ido Somekh
  • Shlomo Almashanu
  • Raz SomechEmail author
Original Article


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.


SCID TREC Newborn screening MHC class II HLA-DR Immunodeficiency 



Hematopoietic stem cell transplantation


Major histocompatibility complex


Newborn screening


Severe combined immunodeficiency


T cell receptor


T cell receptor excision circles


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nufar Marcus
    • 1
    • 2
  • Tali Stauber
    • 3
    • 4
  • Atar Lev
    • 3
    • 4
  • Amos J. Simon
    • 3
    • 4
  • Jerry Stein
    • 2
    • 5
  • Arnon Broides
    • 6
  • Ido Somekh
    • 7
  • Shlomo Almashanu
    • 8
  • Raz Somech
    • 2
    • 3
    • 4
    • 9
    Email author
  1. 1.Allergy and Immunology Unit, Felsenstein Medical Research Center, Kipper Institute of ImmunologySchneider Children’s Medical Center of IsraelPetach TikvaIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Pediatric Department A, Pediatric Immunology ServiceJeffrey Modell Foundation CenterTel HashomerIsrael
  4. 4.Edmond and Lily Safra Children’s HospitalSheba Medical CenterTel HashomerIsrael
  5. 5.Department for Hemato-OncologySchneider Children’s Medical Center of IsraelPetach TikvaIsrael
  6. 6.Pediatric Immunology Clinic, Faculty of Health SciencesSoroka University Medical Center, Ben-Gurion University of the NegevBeer ShevaIsrael
  7. 7.Dr. von Hauner Children’s HospitalUniversity Hospital, LMU MunichMunichGermany
  8. 8.The National Center for Newborn ScreeningMinistry of HealthTel HaShomerIsrael
  9. 9.The National Lab for Confirming Primary Immunodeficiency in Newborn Screening Center for Newborn ScreeningMinistry of HealthTel HaShomerIsrael

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