The HLA-A*30:02~C*18:02~B*57:03 African haplotype identified with the deletion of the HLA-DRB1 gene in individuals from La Réunion Island.

We found a haplotype with the deletion of the HLA-DRB1 gene in two unrelated individuals originated from La Reunion Island, probably resulting from a deletion in the African haplotype A*30:02~C*18:02~B*57:03~DRB1*13:01.

Implication of gammadelta T cells in the human immune response to cytomegalovirus.

In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates. This in vitro expansion was inhibited by anti-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.

What compatibility in 2017 for the haematopoietic stem cell transplantation?

The diversification of potential donors to perform stem cell allografts now enables to propose a compatible graft cell source adapted to the different clinical situations. Transplants with a geno-identical sibling donor, otherwise with the most HLA-compatible unrelated donor, remain the first-line solutions. Alternative transplants allow to graft patients having no donors in international registries, owing to the rarity of their HLA typing. They are carried out with fairly incompatible grafts and are therefore limited by the existence in the recipient of preformed anti-HLA antibodies which predispose to their rejection. The simple prevention of acute Graft-versus-host disease in haplo-identical transplants, as well as the availability of donors, explain why they have very often replaced placental stem cell transplants. These latter remain useful for pediatric patients or in the absence of family donors.

Evidence for a higher resolution of HLA genotyping by a new NGS-based approach.

With more than 16,000 alleles identified, the human leucocyte antigen (HLA) system is one of the most polymorphic regions of the human genome. Regarding the crucial role of HLA compatibility in transplantation and especially in Hematopoietic Stem Cell Transplantation, identification of HLA polymorphisms at a high-resolution level is of major interest. Recently, NGS technology has been proposed which appears to be simpler and more informative than the classical molecular methods such as SSP, SSOr and SBT. In the present report, a new set of NGS reagents and the appropriate associated software for sequence analysis are described. Through different studies, the performances of the system are illustrated and demonstrate that the method herein described overcomes current limitations in performing high-resolution HLA typing in clinical laboratories.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

An HLA-A*2607 variant (A*260702) independently identified in two unrelated French families.

Abstract In this report, we describe the identification of a new variant of the A*2607 allele, named A*260702. This variant was detected independently in two unrelated potential bone marrow donors living in two different regions of France. Molecular typing and mono-allelic sequencing revealed that this allele differs from the original A*2607 allele by a single-nucleotide substitution in codon 56 (GGG --> GGT). This nucleotide change does not affect the amino acid sequence, both triplets coding for a glycine.

Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role.

gammadelta T cells undergo massive expansion in the peripheral blood of renal transplant recipients who are infected with cytomegalovirus (CMV). In a 3-year prospective study, the relationship between the evolution of CMV infection and the kinetics of gammadelta T cell amplification was followed for 10 months after transplantation. Patients with late gammadelta T cell expansion (>/=45 days) had significantly longer (P<.0001) and higher (P<.0003) pp65 antigenemia and more-symptomatic CMV disease than did patients with early expansion. Analysis of data for each patient showed that gammadelta T cell expansion is concomitant with the resolution of CMV infection and disease, regardless of the CMV serologic status of donor and recipient before transplantation. These observations point to gammadelta T cell percentage determination as a new, rapid, and reliable prognosis factor to predict the resolution of CMV infection and strongly suggest that gammadelta T cells play a protective role against CMV infection.