Immunophenotype Anomalies Predict the Development of Autoimmune Cytopenia in 22q11.2 Deletion Syndrome

J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2369-2376. doi: 10.1016/j.jaip.2019.03.014. Epub 2019 Mar 26.


Background: Patients with 22q11.2 deletion syndrome (22q11.2DS) may develop severe thrombocytopenic purpura and hemolytic anemia. There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients.

Objective: To describe the peculiar B and T subpopulation defects in patients with 22q11DS who have developed HA and test if these defects precede the development of HA.

Methods: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without HA (non-HA). A complete immunological evaluation was performed at diagnosis and at the last follow-up including extensive T and B phenotypes.

Results: Immunophenotype at the last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells (26.8% vs 43.2%, P = .003) and recent thymic emigrants (48.6% vs 80.5%, P = .046); decreased class-switched B cells (2.0% vs 5.9%, P = .04) and increased naive B cells (83.5% vs 71.4%, P = .02); increased CD16+/56+ both in absolute number (312 vs 199, P = .009) and percentage (20.0% vs 13.0%, P = .03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0, P = .002) and switched memory B cells ≤2% (OR 44.0, P = .01). The estimated survival curves reached statistical significance, respectively, P = .0001 and P = .002.

Conclusions: Among patients with 22q11.2DS, those with HA have characteristic lymphocyte anomalies that appear considerably before HA onset. Systematic immunophenotyping of patients with 22q11.2DS at diagnosis is advisable for early identification of patients at risk for this severe complication.

Keywords: 22q11.2 deletion syndrome; Autoimmune cytopenia; B immunophenotype; CD4 naïve cells; DiGeorge syndrome; Hemolytic anemia; NK cells; Switched memory B cells; T immunophenotype; Thrombocytopenic purpura.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Autoimmune Diseases / epidemiology
  • Autoimmune Diseases / immunology*
  • B-Lymphocytes / immunology*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • DiGeorge Syndrome / epidemiology
  • DiGeorge Syndrome / immunology*
  • Female
  • Humans
  • Immunophenotyping
  • Lymphopenia / epidemiology
  • Lymphopenia / immunology*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Young Adult