Christopher C. Dvorak, University of California San Francisco
Elie Haddad, University of Montreal
Jennifer Heimall, Perelman School of Medicine at the University of Pennsylvania
Elizabeth Dunn, University of California San Francisco
Morton J. Cowan, University of California San Francisco
Sung-Yun Pai, National Cancer Institute, Bethesda, Md
Neena Kapoor, Children's Hospital Los Angeles
Lisa Forbes Satter, Baylor College of Medicine, Houston, Tex
Rebecca H. Buckley, Duke University Medical Center, Durham, NC
Richard J. O'Reilly, Memorial Sloan Kettering, New York
Sharat Chandra, University of Cincinnati College of Medicine
Jeffrey J. Bednarski, Washington University School of Medicine, St Louis, Mo
Olatundun Williams, Ann and Robert H. Lurie Children's Hospital of Chicago
Ahmad Rayes, Huntsman Cancer Institute at the University of Utah
Theodore B. Moore, UCLA David Geffen School of Medicine
Christen L. Ebens, University of Minnesota, Minneapolis
Blachy J. Davila Saldana, Children's National Hospital, Washington, DC
Aleksandra Petrovic, University of Washington, Seattle Children's Hospital
Deepak Chellapandian, Johns Hopkins All Children's Hospital, St Petersburg, Fla
Geoffrey D. E. Cuvelier, University of Manitoba, Winnipeg, Manitoba
Mark T. Vander Lugt, University of Michigan
Emi H. Caywood, Thomas Jefferson University, Wilmington, Del
Shanmuganathan Chandrakasan, Emory University School of Medicine, Atlanta, Ga
Hesham Eissa, University of Colorado, Aurora
Frederick D. Goldman, University of Alabama, Birmingham
Evan Shereck, Oregon Health & Science University, Portland
Victor M. Aquino, University of Texas Southwestern Medical Center, Dallas
Kenneth B. Desantes, University of Wisconsin School of Medicine, Madison
Lolie Yu, LSU Health Sciences Center - New OrleansFollow
et al

Document Type

Article

Publication Date

11-28-2022

Publication Title

Journal of Allergy and Clinical Immunology

Abstract

Background: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortium's (PIDTC's) prospective and retrospective studies of SCID. Objective: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. Methods: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. Results: According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (< 0.05 × 10(9)/L) characterized typical SCID under the 2022 Definitions. Pathogenic variant(s) in SCID-associated genes was identified in 93% of patients, with 7 genes (IL2RG, RAG1, ADA, IL7R, DCLRE1C, JAK3, and RAG2) accounting for 89% of typical SCID. Three genotypes (RAG1, ADA, and RMRP) accounted for 57% of cases of leaky/atypical SCID; there were 13 other rare genotypes. Patients with leaky/atypical SCID were more likely to be diagnosed at more than age 1 year than those with typical SCID lacking maternal T cells: 20% versus 1% (P < .001). Although repeat testing proved important, an initial CD3 T-cell count of less than 0.05 × 10(9)/L differentiated cases of typical SCID lacking maternal cells from leaky/atypical SCID: 97% versus 7% (P < .001). Conclusions: The PIDTC 2022 Definitions describe SCID and its subtypes more precisely than before, facilitating analyses of SCID characteristics and outcomes.

First Page

547

Last Page

555.e5

PubMed ID

36456360

Volume

151

Issue

2

Comments

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