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J Clin Immunol. 2017 Oct;37(7):707-714. doi: 10.1007/s10875-017-0431-5. Epub 2017 Aug 21.

Detection of Sp110 by Flow Cytometry and Application to Screening Patients for Veno-occlusive Disease with Immunodeficiency.

Author information

1
Immunodeficiency Laboratory, Department of Biomedicine, Basel University Hospital, Basel, Switzerland.
2
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School and Massachusetts General Hospital, Massachusetts, MA, 02114, USA.
3
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
4
Pediatrics Department, Hotel-Dieu Hospital, St Joseph University, Beirut, Lebanon.
5
Institute of Human Genetics, UMR 9002 CNRS-University of Montpellier, 34095, Montpellier Cedex 5, France.
6
Saint George Hospital, University Medical Center, Beirut, Lebanon.
7
Center for Pediatric Pulmonary Medicine, Cleveland Clinic, Cleveland, OH, USA.
8
Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic, Cleveland, OH, USA.
9
Bone Marrow Transplantation Department, Hadassah Hospital, Jerusalem, Israel.
10
Immune Deficiency Genetics Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
11
Immunobiology Laboratory, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland.
12
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
13
Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Keck School of Medicine of University Southern California, Los Angeles, CA, USA.
14
Division of Immunology, Children's Hospital Boston, Boston, MA, USA.
15
Translational Immunology, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland.
16
Division of Rheumatology, Allergy and Immunology, Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
17
Immunodeficiency Laboratory, Department of Biomedicine, Basel University Hospital, Basel, Switzerland. mike.recher@usb.ch.

Abstract

Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC). This approach will fail to identify VODI patients because the disease is not associated with severe T cell lymphopenia at birth; (2) the SP110 gene contains 17 exons, making it a challenge for Sanger sequencing. The recently developed next-generation sequencing (NGS) platforms that can rapidly determine the sequence of all 17 exons are available in only a few laboratories; (3) there is no standard functional assay to test for the effects of novel mutations in Sp110; and (4) it has been difficult to use flow cytometry to identify patients who lack Sp110 because of the low level of Sp110 protein in peripheral blood lymphocytes. We report here a novel flow cytometric assay that is easily performed in diagnostic laboratories and might thus become a standard assay for the evaluation of patients who may have VODI. In addition, the assay will facilitate investigations directed at understanding the function of Sp110.

KEYWORDS:

Combined immunodeficiency; Flow cytometry; Newborn screening; Pneumocystis; Primary immunodeficiency; Sp110; VODI; Veno-occlusive disease with immunodeficiency

PMID:
28825155
PMCID:
PMC6069968
DOI:
10.1007/s10875-017-0431-5
[Indexed for MEDLINE]
Free PMC Article

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