Relationship Between Severity of T cell Lymphopenia and Immune Dysregulation in Patients With DiGeorge Syndrome (22q11.2 Deletions and/or Related TBX1 Mutations): A USIDNET Study

Abstract

To evaluate if the severity of T-cell lymphopenia is associated with immune dysregulation, such as autoimmunity and asthma, in patients with DiGeorge syndrome (DGS) and/or TBX1 mutation.In this study, researchers included 415 patients with DGS and/or TBX1 mutations from the US Immunodeficiency Network registry. Patients with complete and atypical complete DGS were excluded. The median age was 4.6 years (range: 0–45 years).This was a retrospective analysis of 415 patients with DGS and/or TBX1 mutations from the US Immunodeficiency Network registry. Patients were stratified on the basis of severity of initial absolute CD3+ T cells. The rate of infections, autoimmunity, and atopic disease were compared by using χ2 tests and multivariate logistic regression.In this DGS cohort, the median absolute CD3+ T-cell count was 1424 (range: 85–6371 cells/μl). Among the 415 DGS patients, 25% reported congenital heart disease, 4.1% reported autoimmunity, and 6.7% reported asthma. Absolute CD3 counts were lower in those with cardiac disease (P < .001). Patients with absolute CD3+ T cells <50% of age-adjusted normal values were more likely to have reported autoimmunity (odds ratio: 7.56; 95% confidence interval: 1.58 to 36.17; P = .01) and asthma (odds ratio: 4.5; 95% confidence interval: 1.06 to 18.93; P = .04) when compared with those with normal T cell counts. The most commonly reported autoimmune conditions were thyroid disease and cytopenias. Patients with reported autoimmunity more frequently had low CD19+ B cells (P = .002) and low immunoglobulin G (P = .005), when compared with those without autoimmunity. There was no association noted between low CD3+ T cells and immunoglobulin levels or infection rates.Patients with DGS and absolute CD3+ T cells <50% of age-adjusted normal levels had a higher odds of developing autoimmunity and/or asthma, when compared with those with normal T cell counts.Although it is well known that DGS increases the risk for autoimmunity and atopy, in this study, the authors investigated the association between the severity of T-cell lymphopenia and odds of autoimmunity and atopy. Patients with absolute CD3+ T cells <50% of age-adjusted normal levels had a significantly higher odds of developing autoimmunity and/or asthma. This information is useful to providers because it helps us identify those at higher risk for developing autoimmunity and/or asthma and allows us to heighten our surveillance in this population, especially because autoimmunity and/or asthma had increasing frequency with advancing age. This was a large study of DGS patients nationally; however, it was limited by the nature of registry data, which had variable areas of missing data.