Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11·2 microdeletion and partial DiGeorge syndrome

Abstract

SummaryA subgroup of patients with 22q11·2 microdeletion and partial DiGeorge syndrome (pDGS) appears to be susceptible to non-cardiac mortality (NCM) despite sufficient overall CD4 + T cells. To detect these patients, 20 newborns with 22q11·2 microdeletion and congenital heart disease were followed prospectively for 6 years. + T cell numbers were observed in 65%/75%, respectively, of patients in period A (< 1 year) declining to 22%/50%, respectively, of patients in period B (> 1/< 7 years). The percentage of patients with low CTLs (< P10) remained robust until school age (period A: 60%; period B: 50%). Low numbers of CTLs were associated with abnormally low naive CD45RA+ RO -CD4 + T cells. A high-risk (HR) group (n = 11) and a standardrisk (SR) (n = 9) group were identified. HR patients were characterized by low numbers of both naive CD4+ and CTLs and were prone to lethal infectious and lymphoproliferative complications (NCM: four of 11; cardiac mortality: one of 11) while SR patients were not (NCM: none of nine; cardiac mortality: two of nine). Naive CD31 + CD45RA + RO -CD4 + , naive CD45RA + RO -CD4 + T cells as well as TRECs/10 6 mononuclear cells were abnormally low in HR and normal in SR patients. Longitudinal monitoring of naive CD4+ and cytotoxic T cells may help to discriminate pDGS patients at increased risk for NCM.

Clinical Features and Follow-Up in Patients with 22q11.2 Deletion Syndrome

“…Other authors have observed an increased risk of severe infections and autoimmune and lymphoproliferative complications in a specific immunologic subgroup of infants with 22q11DS. 39 Specific studies are needed to identify immunologic markers predictive of a higher risk for severe infections and autoimmune manifestations in patients with 22q11DS.…”

Immunological aspects of 22q11.2 deletion syndrome

“…There are conflicting accounts regarding the gdTCR population with reductions and expansions reported [71,77]. A few patients with T lymphocytopenia appear to be at greater risk of significant viral or candidal infection or early infectious death, particularly those with a combined CD4 and CD8 lymphocytopenia and diminished thymic output, or associated hypoparathyroidism [78,79].…”

Successful Treatment of Sepsis Caused by Staphylococcus lugdunensis in an Adult with 22q11.2 Deletion Syndrome

“…However, the majority of patients only display a partial cellular defect involving reductions in their T cell numbers and mild to moderate immunodeficiency without a predisposition to opportunistic infections such as recurrent candidiasis and/or severe viral infections. In contrast, some patients with 22q11.2DS suffer from fatal infectious diseases such as candidiasis (11), Pneumocystis jiroveci (12) or Epstein-Barr vi- rus infection (13). The occurrence of opportunistic infections is more common among patients with predisposing conditions that impair host defenses including being in an immunocompromised state.…”

“…Although the present patient showed a normal CD4/CD8 ratio and a slightly decreased lymphocyte count, opportunistic infections should be taken into consideration. Patients with 22q11.2DS, might be associated with various immunologic abnormalities including elevated or decreased IgG levels, IgA deficiency, and a decreased B cell subset (12,13,16). Gennery et al (17) described that humoral immunodeficiency is more common than previously recognized in patients with 22q11.2DS, and 26 (81%) of their 32 22q11.2DS patients had severe or recurrent sinopulmonary infection.…”