Defining combined immunodeficiency

Chaim M. Roifman*, Raz Somech, Fotini Kavadas, Linda Pires, Amit Nahum, Ilan Dalal, Eyal Grunebaum

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Although the extreme condition of typical profound T-cell dysfunction (TD), severe combined immunodeficiency (SCID), has been carefully defined, we are currently in the process of better defining less typical T-cell deficiencies, which tend to present with autologous circulating T-cell combined immunodeficiency (CID). Because autologous cells might interfere with the outcome of bone marrow transplantation, protocols usually include conditioning regimens. Therefore it is important to define the numbers of autologous cells usually detected in patients with CID versus those with SCID. Objectives: We sought to determine the number of circulating T cells in patients with SCID as opposed to those with CID, to study their function, and to evaluate their possible detection during newborn screening using T-cell receptor excision circle (TREC) analysis. Methods: Numbers of circulating CD3 + T cells (as determined by means of flow cytometry), in vitro responses to PHA, and TREC levels, all measured at presentation, were compiled from the research charts of the entire cohort of patients followed prospectively for T-cell immunodeficiency at the Hospital for Sick Children. Clinical data were ascertained retrospectively from the patient's hospital charts. Results: One hundred three patients had CD3 + determinations, and 80 of them had a genetic diagnosis. All patients considered to have typical SCID had CD3 + T-cell counts of fewer than 500 cells/μL. Some variability was observed among different genotypes. In vitro responses to PHA were recorded in 88 patients, of whom 68 had a genetic diagnosis. All patients with low CD3 + T-cell numbers (<500 cells/μL) also had markedly decreased responses to PHA (typical SCIDs). However, responses ranged widely in the groups of patients with TD who had more than 500 CD3 + autologous circulating T cells per microliter. Although patients with Omenn syndrome and ζ chain-associated protein, 70 kDa (ZAP70), and purine nucleoside phosphorylase (PNP) deficiencies had low responses, patients with the p.R222C mutation in the IL-2 receptor γ (IL2RG) gene as well as IL-10 receptor and CD40 ligand deficiencies had normal or near-normal mitogen responses. Finally, 51 patients had TREC levels measured. All patients with typical SCID, Omenn syndrome, and ZAP70 deficiency had low TREC levels. In contrast, patients with mutations in forkhead box protein 3 (FOXP3), CD40 ligand (CD40L), and IL-10 receptor α (IL10RA), as well as patients with the p.R222C mutation in the IL2RG gene, had normal TREC levels. Conclusion: Patients with typical SCID can be defined as having fewer than 500 circulating CD3 + T cells. Most patients with autologous T cells still have profound TD, as defined by reduced in vitro function and thymus output. Some patients with conditions including TD have normal TREC levels and will therefore not be detected in a TREC-based newborn screening program.

Original languageEnglish
Pages (from-to)177-183
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jul 2012


  • CD3
  • Combined immunodeficiency
  • T-cell receptor excision circles
  • phytohemagglutinin


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