Chromosome 22q11.2 deletion syndrome (del22q) is one of the most common genetic disorders in humans and results in the triad of cardiac defects, parathyroid hypoplasia, and thymic hypoplasia with variable immune deficiency. Some patients are at increased risk for infection and up to 10% will develop autoimmune disease. The purpose of this study was to further define reduced thymic output and risk for autoimmune disease in this population.
METHODS: This was a case-control study of 17 cases with del22q and age-matched, cardiac surgery status matched controls. Our cohort was young, with the majority of our cases under a year of age. Median age was 9 months with a range of 1 month to 23 years. Nine cases were male. Thirteen cases required cardiac surgery. Peripheral blood samples were assessed by flow cytometry for a variety of immune markers.
RESULTS: Cases showed a significantly lower number of naïve T cells. There was no difference in γδ T-cell number. αβ-T-cell receptor (TCR) repertoire demonstrated expansion of some Vβ families, with no evidence of restriction, and no apparent difference in repertoire variability. Fas expression on T cells was not significantly different. No difference was found in double-negative T cells expressing αβ-TCRs. The activation marker CD25 was higher on T cells, though the expression of HLA-DR, which is also increased with T-cell activation, showed no difference. B cells showed no significant difference in CD27, a marker for the memory cell subset, but CD5 expression, a marker for transitional B cells, was higher in del22q cases. The fraction of CD4+ T cells that were CD4+CD25+ regulatory T cells was higher in del22q cases, though absolute numbers were not significantly different. Del22q cases were also found to have a significantly higher number of natural killer T cells.
CONCLUSIONS: Decreased naïve T cells, TCR repertoire abnormalities, increased lymphocyte activation, increased NK T cells, and subtle B cell defects may all contribute to increased risk of autoimmune disease in patients with del22q. Data from our study and other literature support the hypothesis of decreased thymic output with peripheral homeostatic proliferation in patients with del22q.