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Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B 9) defi ciency and cobalamin (vitamin B 12) defi ciency. Megaloblastic anemia can be diagnosed based on characteristic morphologic and laboratory fi ndings. However, other benign and neoplastic diseases need to be considered, particularly in severe cases. Therapy involves treating the underlying cause-eg, with vitamin supplementation in cases of defi ciency, or with discontinuation of a suspected medication. KEY POINTS The hallmark of megaloblastic anemia is macrocytic anemia (mean corpuscular volume > 100 fL), often associated with other cytopenias. Dysplastic features may be present and can be diffi cult to differentiate from myelodysplastic syndrome. Megaloblastic anemia is most commonly caused by folate defi ciency from dietary defi ciency, alcoholism, or malabsorption syndromes or by vitamin B 12 defi ciency, usually due to pernicious anemia. Both vitamin defi ciencies cause hematologic signs and symptoms of anemia; vitamin B 12 defi ciency also causes neurologic symptoms. Oral supplementation is available for both vitamin defi ciencies; intramuscular vitamin B 12 supplementation should be used in cases involving severe neurologic symptoms or gastric or bowel resection.

GTPase of immunity-associated protein 5 (Gimap5) is linked with lymphocyte survival, autoimmunity, and colitis, but its mechanisms of action are unclear. Here, we show that Gimap5 is essential for the inactivation of glycogen synthase kinase-3β (GSK3β) following T cell activation. In the absence of Gimap5, constitutive GSK3β activity constrains c-Myc induction and NFATc1 nuclear import, thereby limiting productive CD4+ T cell proliferation. Additionally, Gimap5 facilitates Ser389 phosphorylation and nuclear translocation of GSK3β, thereby limiting DNA damage in CD4+ T cells. Importantly, pharmacological inhibition and genetic targeting of GSK3β can override Gimap5 deficiency in CD4+ T cells and ameliorates immunopathology in mice. Finally, we show that a human patient with a GIMAP5 loss-of-function mutation has lymphopenia and impaired T cell proliferation in vitro that can be rescued with GSK3 inhibitors. Given that the expression of Gimap5 is lymphocyte-restricted, we propose that its control of GSK3β is an important checkpoint in lymphocyte proliferation.

IMPORTANCEPatients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other). OBJECTIVE To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.