Natural history of infants with non-SCID T cell lymphopenia identified on newborn screen.

Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; only one patient had an opportunistic infection (vaccine strain VZV infection). Twenty-six (31%) of patients had resolution of TCL during the study period.

Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID).

Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6-85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.