Relationship between human leukocyte antigen alleles and risk of Kaposi’s sarcoma in Cameroon

Several studies published to date report associations between human leukocyte antigen (HLA) alleles and different types of Kaposi’s Sarcoma (KS). However, there is little concordance between the HLA alleles identified and the populations studied. To test whether HLA alleles associate with KS in a Cameroonian case–control study, we performed high-resolution HLA typing in KSHV seropositive individuals. Among HIV-positive individuals, carriers of HLA-B*14:01 were at a significantly higher risk of AIDS-KS (p = 0.033). For HIV-negative patients, a gene-wise comparison of allele frequencies identified the HLA-B (p = 0.008) and -DQA1 (p = 0.002) loci as possible risk factors for endemic KS. Our study provides additional understanding of genetic determinants of KS and their implications in disease pathogenesis. Further validation of these findings is needed to define the functional relevance of these associations

Recipient BCL2 inhibition and NK cell ablation form part of a reduced intensity conditioning regime that improves allo-bone marrow transplantation outcomes

Allogeneic hematopoietic stem cell transplantation (alloSCT) is used to treat over 15,000 patients with acute myeloid leukemia (AML) per year. Donor graft-versus-leukemia (GVL) effect can prevent AML relapse; however, alloSCT is limited by significant toxicity related to conditioning intensity, immunosuppression, opportunistic infections, and graft-versus-host disease (GVHD). Reducing the intensity of conditioning regimens prior to alloSCT has improved their tolerability, but does not alter the pattern of GVHD and has been associated with increased rates of graft rejection and relapse. Here, using a murine pre-clinical model, we describe a novel recipient conditioning approach combining reduced intensity conditioning with either genetic or pharmacological inhibition of NK cell numbers that permits efficient donor engraftment and promotes GVL without inducing GVHD. We show that NK cell-specific deletion of Bcl2 or Mcl1 in mice, or pharmacological inhibition of BCL2 impairs radio-resistant NK cell-mediated rejection of allogeneic engraftment and allows reduction of conditioning intensity below that associated with GVHD priming. The combination of reduced intensity conditioning and NK cell targeting in mice allowed successful donor T cell engraftment and protective immunity against AML while avoiding GVHD. These findings suggest that reduced conditioning in combination with targeted therapies against recipient NK cells may allow the delivery of effective alloSCT against AML while reducing the toxicities associated with more intensive conditioning including GVHD.Yuhao Jiao, Joanne E. Davis, Jai Rautela, Emma M. Carrington, Mandy J. Ludford-Menting ... Benjamin T. Kile ... et al

Carbon sequestration in clay and silt fractions of Brazilian soils under conventional and no-tillage systems

The capacity of soils to sequestrate carbon (C) is mainly related to the formation of organo-mineral complexes. In this study, we investigated the influence of soil management systems on the C retention capacity of soil with an emphasis on the silt and clay fractions of two subtropical soils with different mineralogy and climate. Samples from a Humic Hapludox and a Rhodic Hapludox, clayey soils cultivated for approximately 30 years under no-tillage (NT) and conventional tillage (CT) were collected from six layers distributed within 100-cm soil depth from each site and from an adjacent native forest. After the removal of particulate organic matter (POM), the suspension (<53 μm) was sonicated, the silt and clay fractions were separated in accordance with Stokes' law and the carbon content of whole soil and physical fractions was determined. In the Humic Hapludox, the clay and silt fractions under NT showed a higher maximum C retention (72 and 52 g kg−1, respectively) in comparison to those under CT (54 and 38 g kg−1, respectively). Moreover, the C concentration increase in both fractions under NT occurred mainly in the topsoil (up to 5 cm). The C retention in physical fractions of Rhodic Hapludox varied from 25 to 32 g kg−1, and no difference was observed whether under an NT or a CT management system. The predominance of goethite and gibbsite in the Humic Hapludox, as well as its exposure to a colder climate, may have contributed to its greater C retention capacity. In addition to the organo-mineral interaction, a mechanism of organic matter self-assemblage, enhanced by longer periods of soil non-disturbance, seems to have contributed to the carbon stabilization in both soils