Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.

BACKGROUND: Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation. OBJECTIVES: Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC. METHODS: Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation. RESULTS: Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19hiCD21lo B cells, and double negative cells and reduction in CD4 naïve T cells and regulatory T cells. First-line treatment for 17/29 (59%) included corticosteroids and/or high-dose immunoglobulin replacement therapy. Other overlapping therapies included eltrombopag, rituximab, and T cell immunomodulators. CONCLUSIONS: AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens.

Two Unique Cases of X-linked SCID: A Diagnostic Challenge in the Era of Newborn Screening.

In the era of newborn screening (NBS) for severe combined immunodeficiency (SCID) and the possibility of gene therapy (GT), it is important to link SCID phenotype to the underlying genetic disease. In western countries, X-linked interleukin 2 receptor gamma chain (IL2RG) and adenosine deaminase (ADA) deficiency SCID are two of the most common types of SCID and can be treated by GT. As a challenge, both IL2RG and ADA genes are highly polymorphic and a gene-based diagnosis may be difficult if the variant is of unknown significance or if it is located in non-coding areas of the genes that are not routinely evaluated with exon-based genetic testing (e.g., introns, promoters, and the 5'and 3' untranslated regions). Therefore, it is important to extend evaluation to non-coding areas of a SCID gene if the exon-based sequencing is inconclusive and there is strong suspicion that a variant in that gene is the cause for disease. Functional studies are often required in these cases to confirm a pathogenic variant. We present here two unique examples of X-linked SCID with variable immune phenotypes, where IL2R gamma chain expression was detected and no pathogenic variant was identified on initial genetic testing. Pathogenic IL2RG variants were subsequently confirmed by functional assay of gamma chain signaling and maternal X-inactivation studies. We propose that such tests can facilitate confirmation of suspected cases of X-linked SCID in newborns when initial genetic testing is inconclusive. Early identification of pathogenic IL2RG variants is especially important to ensure eligibility for gene therapy.

The effect of a 473-mL (16-oz) water drink on vasovagal donor reaction rates in high-school students.

BACKGROUND: Recent clinical studies found that a water drink prevented orthostatic hypotension in healthy subjects subjected to a tilt-table test. A water drink was tested as a method to decrease vasovagal donor reactions in high-school students. STUDY DESIGN AND METHODS: A total of 8894 high-school donations in Fall 2004 and 2005 were assigned to groups receiving or not receiving a 473-mL water drink after acceptance for whole-blood donation. In addition, 4340 donations in 2004 were reduced to 2895 donations ("balanced 2004 group") with an algorithm that equally balanced the donors between the water and no water arms. RESULTS: The donor reaction rate was 9.9 percent (349 reactions/3534 donations) in donors given a water drink versus 12.5 percent (668 reactions/5360 donations; p = 0.0002) in donors not given a water drink. Donors given a water drink had a 21 percent reduction in their donor reaction rate. The main benefit of water was in Caucasian, first-time donors. In the balanced 2004 group, the donor reaction rate was 10.6 percent (153 reactions/1438 donations) in donors given a water drink versus 14.8 percent (216 reactions/1457 donations; p = 0.0008) in donors not given a water drink. Donors given a water drink in the balanced 2004 group had a 28 percent reduction in their donor reaction rate. The use of water did not interfere with donor processing and was judged by collection staff as easy to implement. CONCLUSION: A 473-mL water drink decreased the vasovagal donor reaction rate in high-school donors by 21 percent, but to varying degrees in different subpopulations.