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Use of Genetic Testing for Primary Immunodeficiency Patients

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A Correction to this article was published on 21 May 2018

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Abstract

Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey. Finally, we delineate the CIS’s recommendations for the use of genetic testing in light of these issues.

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Change history

  • 21 May 2018

    The original version of this article unfortunately contained mistakes in some of the author names and affiliations. The correct list of author names and affiliations is below, with the corrections in bold.

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Author information

Authors and Affiliations

  1. Division of Allergy and Immunology, Children’s Hospital of Philadelphia, University of Pennsylvania, Wood Building 3rd Floor, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Jennifer R. Heimall & Sarah E. Henrickson

  2. Allergy and Immunology Division, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

    David Hagin

  3. Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Baylor College of Medicine, Houston, TX, USA

    Joud Hajjar

  4. Wherry Lab, University of Pennsylvania, Philadelphia, PA, USA

    Sarah E. Henrickson

  5. Division of Infectious Disease & Immunology, Connecticut Children’s Medical Center, Hartford, CT, USA

    Hillary S. Hernandez-Trujillo

  6. CT Asthma and Allergy Center, West Hartford, CT, USA

    Hillary S. Hernandez-Trujillo

  7. The Charles Bronfman Institute of Personalized Medicine, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yuval Tan

  8. Allergy/Immunology, Emory University, Atlanta, GA, USA

    Lisa Kobrynski

  9. Division of Allergy-Immunology, LSU Health Sciences Center, Children’s Hospital, New Orleans, LA, USA

    Kenneth Paris

  10. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Troy R. Torgerson

  11. Pediatrics and Microbiology and Molecular Genetics Section of Pediatric Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA

    James W. Verbsky

  12. Department of Pediatrics, Medical City Children’s Hospital, Dallas, TX, USA

    Richard L. Wasserman

  13. Department of Immunology and Microbiology, Department of Pediatrics, Division of Allergy and Immunology, University of Colorado, School of Medicine, Aurora, CO, USA

    Elena W. Y. Hsieh

  14. Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Jack J. Blessing

  15. Division of Immunology, Boston Children’s Hospital, Boston, MA, USA

    Janet S. Chou

  16. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Janet S. Chou

  17. Division of Asthma, Allergy and Clinical Immunology, University of Virginia Health System, Charlottesville, VA, USA

    Monica G. Lawrence

  18. Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Rebecca A. Marsh

  19. NIH Clinical Center, Bethesda, MD, USA

    Sergio D. Rosenzweig

  20. Center for Human Immunobiology, Texas Children’s Hospital, Houston, TX, USA

    Jordan S. Orange

  21. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Jordan S. Orange

  22. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Roshini S. Abraham

Authors
  1. Jennifer R. Heimall
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  2. David Hagin
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  3. Joud Hajjar
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  4. Sarah E. Henrickson
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  5. Hillary S. Hernandez-Trujillo
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  6. Yuval Tan
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  7. Lisa Kobrynski
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  8. Kenneth Paris
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  9. Troy R. Torgerson
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  10. James W. Verbsky
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  11. Richard L. Wasserman
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  12. Elena W. Y. Hsieh
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  13. Jack J. Blessing
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  14. Janet S. Chou
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  15. Monica G. Lawrence
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  16. Rebecca A. Marsh
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  17. Sergio D. Rosenzweig
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  18. Jordan S. Orange
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  19. Roshini S. Abraham
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Corresponding author

Correspondence to Jennifer R. Heimall.

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Conflict of Interest

The authors declared that they have no conflict of interest, except for the following:

Jennifer Heimall, MD: ADMA Consultant; CSL Behring speaker panel

Sarah Henrickson, MD, PhD: Horizon Pharmaceuticals advisory board

Kenneth Paris, MD, MPH: Shire Advisory Board Participant, Speaker, Clinical Trial Investigator; CSL Behring Advisory Board Participant

Troy Torgerson, MD, PhD: Director Seattle Children’s Immunology Diagnostic Lab, Seattle, WA

Jordan Orange, MD, PhD: Shire Consultant, Grifols Consultant

Additional information

Summary Statements

1. The Clinical Immunology Society (CIS) supports the use of genetic testing by clinical immunologists to provide state of the art diagnosis and precision treatment for primary immunodeficiency patients.

2. Genetic testing provides the ability to make a definitive diagnosis, project prognosis based on genotype-phenotype association, utilize available targeted therapy and inform family planning decisions.

3. Genetic counseling should be provided before and after genetic testing with an immunologist or genetic counselor with expertise in primary immunodeficiency.

4. The choice of genetic test for a given patient should be made by the immunologist within the context of the patient’s clinical history and other phenotypic and functional results.

5. The use and application of individual Sanger sequencing tests, gene panels and broader genomic approaches has different and rapidly changing cost and turn-around-time implications.

6. In patients in whom initial genetic testing is not conclusive, follow up testing may be needed to determine a conclusive diagnosis.

7. Genetic testing should not be a pre-requisite confirmatory test to initiate or continue disorder-specific or supportive therapy such as immunoglobulin replacement in patients where the clinical history and routine testing demonstrate a clear need for the therapy.

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Heimall, J.R., Hagin, D., Hajjar, J. et al. Use of Genetic Testing for Primary Immunodeficiency Patients. J Clin Immunol 38, 320–329 (2018). https://doi.org/10.1007/s10875-018-0489-8

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  • DOI: https://doi.org/10.1007/s10875-018-0489-8

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