Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia

Roshini S. Abraham, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, OH, USA. Electronic address: Roshini.Abraham@nationwidechildrens.org.
Amrita Basu, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, OH, USA.
Jennifer R. Heimall, Division of Allergy and Immunology, Children's Hospital of Philadelphia, PA, USA.
Elizabeth Dunn, Division of Allergy, Immunology, and Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Alison Yip, Division of Allergy, Immunology, and Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Malika Kapadia, Division of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Department of Pediatrics, Harvard University Medical School, Boston, MA, USA.
Neena Kapoor, Transplantation and Cellular Therapy Program, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lisa Forbes Satter, Pediatrics, Immunology, Allergy and Rheumatology, Baylor College of Medicine, Houston, TX, USA.
Rebecca Buckley, Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC, USA.
Richard O'Reilly, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Geoffrey D. Cuvelier, Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
Sharat Chandra, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Jeffrey Bednarski, Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Sonali Chaudhury, Division of Hematology, Oncology, and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago-Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Theodore B. Moore, Division of Hematology/Oncology, Mattel Children's Hospital at UCLA, Los Angeles, CA, USA.
Hilary Haines, Division of Pediatric Hematology-Oncology and Bone Marrow Transplant, University of Alabama at Birmingham, Birmingham, AL, USA.
Blachy J. Dávila Saldaña, Division of Blood and Marrow Transplantation, Children's National Hospital-George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Deepakbabu Chellapandian, Blood and Marrow Transplant, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
Ahmad Rayes, Division of Pediatric Hematology and Oncology, Intermountain Primary Childrens Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, UT, USA.
Karin Chen, Department of Pediatrics, University of Washington-Seattle Children's Hospital, Seattle, WA, USA.
Emi Caywood, Nemours Children's Health Delaware, Thomas Jefferson University, Wilmington, DE, USA.
Shanmuganathan Chandrakasan, Bone Marrow Transplantation Program, Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Mark Thomas Lugt, Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI, USA.
Christen Ebens, Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy, University of Minnesota, Minneapolis, MN, USA.
Pierre Teira, Pediatric Immunology and Rheumatology Division, CHU Sainte-Justine, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
Evan Shereck, Division of Pediatric Hematology/Oncology, Oregon Health and Science University, Portland, OR, USA.
Holly Miller, Phoenix Children's Hospital, Phoenix, AZ, USA.
Victor Aquino, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hesham Eissa, Division of Pediatric Hematology-Oncology-BMT, University of Colorado, Aurora, CO, USA.
Lolie C. Yu, Division of Pediatric Hematology-Oncology/HSCT, LSUHSC and Children's Hospital, New Orleans, LA, USA.
Alfred Gillio, Institute for Pediatric Cancer and Blood Disorders, Hackensack University Medical Center, Hackensack, NJ, USA.
Lisa Madden, Pediatric Blood and Marrow Transplantation Program, Texas Transplant Institute, Methodist Children's Hospital, San Antonio, TX, USA.

Document Type

Journal Article

Publication Date

4-1-2024

Journal

Clinical immunology (Orlando, Fla.)

Volume

261

DOI

10.1016/j.clim.2024.109942

Keywords

Mitogen; PHA; PIDTC; SCID; Severe combined immunodeficiency; T-cell lymphopenia; T-cell proliferation

Abstract

Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.02). Further, in patients with CD3+ T cell counts between 51 and 300 cells/μL, there was a higher proliferative response with the PHA flow assay compared to the H-T assay (p < 0.0001), suggesting that the method of analysis influences the resolution and interpretation of PHA results. Importantly, we observed many SCID patients with profound T cell lymphopenia having normal T cell proliferation when assessed by flow cytometry. We recommend this test be considered only as supportive in the diagnosis of typical SCID.

Department

Pediatrics

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