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The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions.

Publication ,  Journal Article
Dvorak, CC; Haddad, E; Heimall, J; Dunn, E; Cowan, MJ; Pai, S-Y; Kapoor, N; Satter, LF; Buckley, RH; O'Reilly, RJ; Chandra, S; Bednarski, JJ ...
Published in: J Allergy Clin Immunol
February 2023

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 × 109/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 × 109/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.

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Published In

J Allergy Clin Immunol

DOI

EISSN

1097-6825

Publication Date

February 2023

Volume

151

Issue

2

Start / End Page

547 / 555.e5

Location

United States

Related Subject Headings

  • Severe Combined Immunodeficiency
  • Retrospective Studies
  • Prospective Studies
  • Infant, Newborn
  • Infant
  • Humans
  • Homeodomain Proteins
  • Allergy
  • 1107 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
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Dvorak, C. C., Haddad, E., Heimall, J., Dunn, E., Cowan, M. J., Pai, S.-Y., … Puck, J. M. (2023). The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions. J Allergy Clin Immunol, 151(2), 547-555.e5. https://doi.org/10.1016/j.jaci.2022.10.021
Dvorak, Christopher C., Elie Haddad, Jennifer Heimall, Elizabeth Dunn, Morton J. Cowan, Sung-Yun Pai, Neena Kapoor, et al. “The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions.J Allergy Clin Immunol 151, no. 2 (February 2023): 547-555.e5. https://doi.org/10.1016/j.jaci.2022.10.021.
Dvorak CC, Haddad E, Heimall J, Dunn E, Cowan MJ, Pai S-Y, et al. The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions. J Allergy Clin Immunol. 2023 Feb;151(2):547-555.e5.
Dvorak, Christopher C., et al. “The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions.J Allergy Clin Immunol, vol. 151, no. 2, Feb. 2023, pp. 547-555.e5. Pubmed, doi:10.1016/j.jaci.2022.10.021.
Dvorak CC, Haddad E, Heimall J, Dunn E, Cowan MJ, Pai S-Y, Kapoor N, Satter LF, Buckley RH, O’Reilly RJ, Chandra S, Bednarski JJ, Williams O, Rayes A, Moore TB, Ebens CL, Davila Saldana BJ, Petrovic A, Chellapandian D, Cuvelier GDE, Vander Lugt MT, Caywood EH, Chandrakasan S, Eissa H, Goldman FD, Shereck E, Aquino VM, Desantes KB, Madden LM, Miller HK, Yu L, Broglie L, Gillio A, Shah AJ, Knutsen AP, Andolina JP, Joshi AY, Szabolcs P, Kapadia M, Martinez CA, Parrot RE, Sullivan KE, Prockop SE, Abraham RS, Thakar MS, Leiding JW, Kohn DB, Pulsipher MA, Griffith LM, Notarangelo LD, Puck JM. The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions. J Allergy Clin Immunol. 2023 Feb;151(2):547-555.e5.
Journal cover image

Published In

J Allergy Clin Immunol

DOI

EISSN

1097-6825

Publication Date

February 2023

Volume

151

Issue

2

Start / End Page

547 / 555.e5

Location

United States

Related Subject Headings

  • Severe Combined Immunodeficiency
  • Retrospective Studies
  • Prospective Studies
  • Infant, Newborn
  • Infant
  • Humans
  • Homeodomain Proteins
  • Allergy
  • 1107 Immunology