Correction of both immunodeficiency and hypoparathyroidism by thymus transplantation in complete DiGeorge Syndrome

Combined immune deficiency due to athymia in patients with complete DiGeorge syndrome can be corrected by allogeneic thymus transplantation. Hypoparathyroidism is a frequent concomitant clinical problem in these patients, which persists after thymus transplantation. Cotransplantation of allogeneic thymus and parental parathyroid tissue has been attempted but does not achieve durable correction of the patients' hypoparathyroidism due to parathyroid graft rejection. Surprisingly, we observed correction of hypoparathyroidism in one patient after thymus transplantation. Immunohistochemical analysis and fluorescence in situ hybridization confirmed the presence of allogeneic parathyroid tissue in the patient's thymus transplant biopsy. Despite a lack of HLA‐matching between thymus donor and recipient, the reconstituted immune system displays tolerance toward the thymus donor. Therefore we expect this patient's hypoparathyroidism to be permanently cured. It is recognised that ectopic parathyroid tissue is not infrequently found in the thymus. If such thymuses could be identified, we propose that their use would offer a compelling approach to achieving lasting correction of both immunodeficiency and hypoparathyroidism

Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19(+) B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology

Decision Support System for Site-Specific Fertilizer Recommendations in Cassava Production in Southern Togo

The Quantitative Evaluation of the Fertility of Tropical Soils (QUEFTS) model recommended as a decision support tool for deriving optimal site-specific fertilizer rates for cassava has limited ability to estimate water-limited yields. We assessed potential and water-limited yields based on the light interception and utilization (LINTUL) modelling approach in order to enhance the determination of fertilizer requirements for cassava production in Southern Togo. Data collected in 2 years field experiments in Sevekpota and Djakakope were used. Potential ranged from 12.2 to 17.6 Mg ha−1, and water-limited yields from 10.4 to 14.5 Mg ha−1. The simulated average fertilizer requirements were 121 kg N, 2 kg P and no K ha−1 for a target yield of 9.3 Mg ha−1 at Sevekpota, and 103 kg N, 6 kg P and 175 kg K ha−1 for a target yield of 9.7 Mg ha−1 at Djakakope. The variability of fertilizer requirements was attributed to differences in indigenous soil fertility and water-limited yields. The latter correlated well with rainfall variability over years and sites. Integrating LINTUL output with QUEFTS helped account for location-specific weather seasonal variability and enhanced assessment of fertilizer requirement for cassava production in Southern Togo