2,271 research outputs found
A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers
No full textBackground and Aims: Chronic infection with the hepatitis B virus (HBV) is a major health issue worldwide. Recently, single nucleotide polymorphisms (SNPs) within the human leukocyte antigen (HLA)-DP locus were identified to be associated with HBV infection in Asian populations. Most significant associations were observed for the A alleles of HLA-DPA1 rs3077 and HLA-DPB1 rs9277535, which conferred a decreased risk for HBV infection. We assessed the implications of these variants for HBV infection in Caucasians.
Methods: Two HLA-DP gene variants (rs3077 and rs9277535) were analyzed for associations with persistent HBV infection and with different clinical outcomes, i.e., inactive HBsAg carrier status versus progressive chronic HBV (CHB) infection in Caucasian patients (n = 201) and HBsAg negative controls (n = 235).
Results: The HLA-DPA1 rs3077 C allele was significantly associated with HBV infection (odds ratio, OR = 5.1, 95% confidence interval, CI: 1.9–13.7; p = 0.00093). However, no significant association was seen for rs3077 with progressive CHB infection versus inactive HBsAg carrier status (OR = 2.7, 95% CI: 0.6–11.1; p = 0.31). In contrast, HLA-DPB1 rs9277535 was not associated with HBV infection in Caucasians (OR = 0.8, 95% CI: 0.4–1.9; p = 1).
Conclusions: A highly significant association of HLA-DPA1 rs3077 with HBV infection was observed in Caucasians. However, as a differentiation between different clinical courses of HBV infection was not possible, knowledge of the HLA-DPA1 genotype cannot be translated into personalized anti-HBV therapy approaches
Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses
No full textSince HLA-restricted cytotoxic T-cell responses select specific polymorphisms in HIV-1 sequences and HLA diversity is relatively static in human populations, we investigated the use of peptide epitopes based on sites of HLA-associated adaptation in HIV-1 sequences to stimulate and detect T-cell responses ex vivo. These "HLA-optimised" peptides captured more HIV-1 Nef-specific responses compared with overlapping peptides of a single consensus sequence, in interferon-γ enzyme linked immunospot assays. Sites of immune selection can reveal more immunogenic epitopes in HLA-diverse populations and offer insights into the nature of HLA-epitope targeting, which could be applied in vaccine design
Identification of a novel HLA-C*08 allele, HLA-C*08:01:20
No full textHLA-C*08:01:20 differs from C*08:01:01 by a single nucleotide substitution at position 93 of exon 2.SCI(E)EDITORIAL MATERIAL3178-+9
Identification of a novel HLA-A*02 allele, HLA-A*02:622N
No full textHLA-A*02:622N differs from A*02:07:01 by a single nucleotide substitution at position 420 of exon 3.? 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.SCI(E)PubMedEDITORIAL [email protected]
Identification of a novel HLA-DRB1*07 allele, HLA-DRB1*07:01:19
No full textHLA-DRB1*07:01:19 differs from DRB1*07:01:01:01 by a single nucleotide substitution at position 261 of exon 2.? 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.SCI(E)PubMedEDITORIAL [email protected]
Design and implementation of a HLA inter-federation bridge
No full textIn this paper, we discuss the design and implementation of a HLA inter-federation bridge. Our works are mainly motivated by the scalability and security problems, but we also consider the use of bridges for interoperability purposes. We describe several bridge topologies, including linear and cyclic inter-federations. We discuss problems raised by bridge federates and the use of different RTI implementations. We detail several solutions, leading to the design and implementation of a bridge prototype. Then we present our current results, and on-going works concerning performance improvements, interoperability, and security purposes
Towards an HLA Run-time Infrastructure with Hard Real-time Capabilities
No full textOur work takes place in the context of the HLA standard and its application in real-time systems context. The HLA standard is inadequate for taking into consideration the different constraints involved in real-time computer systems. Many works have been invested in order to providing real-time capabilities to Run Time Infrastructures (RTI) to run real time simulation. Most of these initiatives focus on major issues including QoS guarantee, Worst Case Transit Time (WCTT) knowledge and scheduling services provided by the underlying operating systems. Even if our ultimate objective is to achieve real-time capabilities for distributed HLA federations executions, this paper describes a preliminary work focusing on achieving hard real-time properties for HLA federations running on a single computer under Linux operating systems. Our paper proposes a novel global bottom up approach for designing real-time Run time Infrastructures and a formal model for validation of uni processor to (then) distributed real-time simulation with CERTI
CD4+ T cell epitopes of FliC conserved between strains of Burkholderia: implications for vaccines against melioidosis and cepacia complex in cystic fibrosis.
No full textBurkholderia pseudomallei is the causative agent of melioidosis characterized by pneumonia and fatal septicemia and prevalent in Southeast Asia. Related Burkholderia species are strong risk factors of mortality in cystic fibrosis (CF). The B. pseudomallei flagellar protein FliC is strongly seroreactive and vaccination protects challenged mice. We assessed B. pseudomallei FliC peptide binding affinity to multiple HLA class II alleles and then assessed CD4 T cell immunity in HLA class II transgenic mice and in seropositive individuals in Thailand. T cell hybridomas were generated to investigate cross-reactivity between B. pseudomallei and the related Burkholderia species associated with Cepacia Complex CF. B. pseudomallei FliC contained several peptide sequences with ability to bind multiple HLA class II alleles. Several peptides were shown to encompass strong CD4 T cell epitopes in B. pseudomallei-exposed individuals and in HLA transgenic mice. In particular, the p38 epitope is robustly recognized by CD4 T cells of seropositive donors across diverse HLA haplotypes. T cell hybridomas against an immunogenic B. pseudomallei FliC epitope also cross-reacted with orthologous FliC sequences from Burkholderia multivorans and Burkholderia cenocepacia, important pathogens in CF. Epitopes within FliC were accessible for processing and presentation from live or heat-killed bacteria, demonstrating that flagellin enters the HLA class II Ag presentation pathway during infection of macrophages with B. cenocepacia. Collectively, the data support the possibility of incorporating FliC T cell epitopes into vaccination programs targeting both at-risk individuals in B. pseudomallei endemic regions as well as CF patients
HLA-CSPIF panel on commercial off-the-shelf distributed simulation
No full textCommercial-off-the-shelf (COTS) simulation packages are widely used in many areas of industry. Several research groups are attempting to integrate distributed simulation principles and techniques with these packages to potentially give us COTS distributed simulation. The High Level Architecture-COTS Simulation Package Interoperation Forum (HLA-CSPIF) is a group of researchers and practitioners that are studying methodological and technological issues in this area. This panel paper presents the views of four members of this forum on the technical problems that must be overcome for this emerging field to be realized
Seronegative spondyloarthropathies : a review : part II: genetics and pathogenesis
No full textIn none of the spondyloarthropathies is the pathogenesis well understood. Much of the investigation into the aetio-pathogenesis of these diseases has focused on the association with HLA-B27 and the known triggering potential of certain infectious agents. In this article the author describes that the HLA linked genes which is subdivided into three groups, class I, class II and class III, which are structurally and functionally distinct from each other.peer-reviewe
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