The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions.

Abstract

Severe combined immunodeficiency (SCID) results from defects in the differentiation of hematopoietic stem cells into mature T lymphocytes, with additional lymphoid lineages affected in particular genotypes. In 2014, the Primary Immune Deficiency Treatment Consortium published criteria for diagnosing SCID, which are now revised to incorporate contemporary approaches. Patients with typical SCID must have less than 0.05 × 109 autologous T cells/L on repetitive testing, with either pathogenic variant(s) in a SCID-associated gene, very low/undetectable T-cell receptor excision circles or less than 20% of CD4 T cells expressing naive markers, and/or transplacental maternally engrafted T cells. Patients with less profoundly impaired autologous T-cell differentiation are designated as having leaky/atypical SCID, with 2 or more of these: low T-cell numbers, oligoclonal T cells, low T-cell receptor excision circles, and less than 20% of CD4 T cells expressing naive markers. These patients must also have either pathogenic variant(s) in a SCID-associated gene or reduced T-cell proliferation to certain mitogens. Omenn syndrome requires a generalized erythematous rash, absent transplacentally acquired maternal engraftment, and 2 or more of these: eosinophilia, elevated IgE, lymphadenopathy, hepatosplenomegaly. Thymic stromal defects and other causes of secondary T-cell deficiency are excluded from the definition of SCID. Application of these revised Primary Immune Deficiency Treatment Consortium 2022 Definitions permits precise categorization of patients with T-cell defects but does not imply a preferred treatment strategy.

• Authors: Christopher C Dvorak, Elie Haddad, Jennifer Heimall, Elizabeth Dunn, Rebecca H Buckley, Donald B Kohn, Morton J Cowan, Sung-Yun Pai, Linda M Griffith, Geoffrey D E Cuvelier, Hesham Eissa, Ami J Shah, Richard J O'Reilly, Michael A Pulsipher, Nicola A M Wright, Roshini S Abraham, Lisa Forbes Satter, Luigi D Notarangelo, Jennifer M Puck
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 151 Issue 2 Pg. 539-546 (02 2023) ISSN: 1097-6825 [Electronic] United States
• PMID: 36456361 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Antigen, T-Cell

Topics

• Humans
• Severe Combined Immunodeficiency (diagnosis, genetics, therapy)
• Immunologic Deficiency Syndromes (therapy)
• CD4-Positive T-Lymphocytes
• Thymus Gland
• Receptors, Antigen, T-Cell (genetics)