HLA genetic study from United Arab Emirates (UAE), Abu Dhabi

Emiratis belong to the United Arab Emirates (UAE) country. UAE is placed at the East part of the Arabian Peninsula, protruding into the Arabia Gulf and was populated since 130,000 years ago. First humans migrating out of Africa went probably across this territory. HLA-A, -B, -C, -DRB1, -DQB1, -DQA1 were typed in order to obtain HLA profile for clinical, epidemiological and population genetics studies. Twenty different HLA-A, thirty-five HLA-B and twenty-two HLA-C class I alleles were detected; twenty-seven different HLA-DRB1, fourteen HLA-DQB1 and twelve HLA-DQA1 class II alleles were found. Most frequent extended HLA haplotypes are also depicted. People are present in this area since prehistoric ages according to archaeological studies; the “Out of Africa” eastern migration may have affected the present day population composition.     

The outcome of the endothelial precursor cell crossmatch test in lymphocyte crossmatch positive and negative patients evaluated for living donor kidney transplantation

The presence of human leukocyte antigen (HLA) and non-HLA antibodies (Abs) in kidney transplant recipients is associated with graft rejections. This study reports the results of an endothelial precursor cell crossmatch (EPCXM) test for detection of non-HLA Abs and its correlation to lymphocyte crossmatch (LXM) test results, the degree and type of sensitization, and transplantation (Tx) outcome in patients evaluated for living donor (LD) kidney transplantation (KTx). Patients were tested before any pre-transplantation (pre-Tx) treatment and at Tx. Pre-Tx treatments included B cell depletion and Ab removal. Patient records were reviewed for assessment of renal graft function, results of biopsies, and identification of complications affecting the graft. Pre-Tx sera from 32% of the LD patients had IgG and/or IgM-binding donor EPCs. Twenty-five percent of the patients were EPCXM IgM+. Of the patients with negative LXM tests, 25% had EPC Abs mainly of IgM class not reactive with HLA. There was no difference in rejection frequency or serum creatinine levels between the EPCXM+ and EPCXM− groups. The pre-Tx EPCXM+ group had significantly more patients with delayed graft function. Prospective studies with appropriate control groups are needed to establish whether pre-treatments aiming at removing anti-endothelial cell antibodies, as detected by the EPCXM pre-Tx, have a beneficial effect on short-term and long-term graft survival.     

Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A

One of many protein-protein interactions modulated upon DNA damage is that of the single-stranded DNA-binding protein, replication protein A (RPA), with the p53 tumor suppressor. Here we report the crystal structure of RPA residues 1-120 (RPA70N) bound to the N-terminal transactivation domain of p53 (residues 37-57; p53N) and, by using NMR spectroscopy, characterize two mechanisms by which the RPA/p53 interaction can be modulated. RPA70N forms an oligonucleotide/oligosaccharide-binding fold, similar to that previously observed for the ssDNA-binding domains of RPA. In contrast, the N-terminal p53 transactivation domain is largely disordered in solution, but residues 37-57 fold into two amphipathic helices, H1 and H2, upon binding with RPA70N. The H2 helix of p53 structurally mimics the binding of ssDNA to the oligonucleotide/oligosaccharide-binding fold. NMR experiments confirmed that both ssDNA and an acidic peptide mimicking a phosphorylated form of RPA32N can independently compete the acidic p53N out of the binding site. Taken together, our data suggest a mechanism for DNA damage signaling that can explain a threshold response to DNA damage.