IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

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We quantified neutrophils and neutrophil progenitors, and assessed granulocyte colony-stimulating factor (G-CSF) production in the liver and bone marrow of 20 human abortuses after elective pregnancy termination between 14 and 24 wk of gestation. Mature neutrophils were not observed in any of the liver specimens, but were present in the bone marrow as early as 14 wk. The concentrations of neutrophils in the fetal marrow were extremely low, by comparison with term infants and adults, with less than 5% of the nucleated cells being segmented neutrophils, band neutrophils, or metamyelocytes compared with 31-69% in term infants. Despite the low neutrophil populations, progenitors which had the capacity for clonal maturation into neutrophils in vitro were abundant in the fetal liver and fetal bone marrow. In addition, such progenitors had a dose-response relationship to recombinant G-CSF similar to that of progenitors from the bone marrow of healthy adults. At each gestational age tested, stimulation of mononuclear cells from fetal liver with IL-la generated less G-CSF protein and fewer G-CSF mRNA transcripts than did stimulation of mononuclear cells from fetal bone marrow. Mononuclear cells from the fetal bone marrow produced less G-CSF protein and mRNA than did mononuclear cells from the blood of The NSP is the sum of all segmented neutrophils, band neutrophils, and metamyelocytes held in reserve for ready release into the circulation (1). Rat pups delivered prematurely have a much smaller NSP, per g of body weight, than do those delivered at term, and pups delivered at term have a smaller NSP than do adult rats (2-6). It is unknown, however, whether this observation applies to humans. Studies employing cells

Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting.