Foxp3+ regulatory T cells (Tregs) are required for immune homeostasis. One notable distinction between conventional T cells (Tconv) and Tregs is differential phosphatidylinositol 3-kinase (PI3K) activity: only Tconv downregulate PTEN, the primary negative regulator of PI3K, upon activation. Here, we show that control of PI3K in Tregs is essential for lineage homeostasis and stability. Mice lacking Pten in Tregs developed an autoimmune-lymphoproliferative disease characterized by excessive TH1 responses and B cell activation. Diminished control of PI3K activity in Tregs led to reduced CD25 expression, accumulation of Foxp3+CD25− cells and ultimately, loss of Foxp3 expression in these cells. Collectively, these data demonstrate that control of PI3K signaling by PTEN in Tregs is critical to maintain their homeostasis, function and stability.

Differences in race/ethnicity can significantly affect the results obtained from MDRD-based eGFR equation. It is highly recommended that each population should validate eGFR equations before applying the equation in epidemiologic studies or clinical use.

Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen-positive [HBsAg(þ)] donors to HBsAg(À) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow-up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti-HBs) levels. The present retrospective, longitudinal study (clinicaltrial. gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(À) recipients with anti-HBs titer above 100 mIU/mL undergoing KT from HBsAg(þ) donors (n ¼ 43) and HBsAg(À) donors (n ¼ 86). During the median follow-up duration of 58.2 months (range 16.7-158.3 months), there were no significant differences in graft and patient survivals. No HBV-infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(þ) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV-associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(þ) donors with no HBV prophylaxis (n ¼ 20) provided comparable outcomes with those treated with lamivudine alone (n ¼ 21) or lamivudine in combination with HBV immunoglobulin (n ¼ 2). In conclusion, KT without HBV prophylaxis from HBsAg(þ) donors without hepatitis B viremia to HBsAg(À) recipients with anti-HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.