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  1. Article ; Online: Homozygous HLA-DQB1*06:02 combined with T-cell receptor alpha polymorphism results in narcolepsy onset - A familial case report.

    Jervis, Steven / Payton, Antony / Verma, Arpana / Thomasson, Rachel / Poulton, Kay

    International journal of immunogenetics

    2024  

    Abstract: Narcolepsy is a life-long neurological disorder with well-established genetic risk factors. Human leukocyte antigen-DQB1*06:02 remains the strongest genetic predeterminant; however, polymorphisms in genes encoding the T-cell receptor alpha chain are also ...

    Abstract Narcolepsy is a life-long neurological disorder with well-established genetic risk factors. Human leukocyte antigen-DQB1*06:02 remains the strongest genetic predeterminant; however, polymorphisms in genes encoding the T-cell receptor alpha chain are also strongly linked. This case report shows the inheritance pathway of these genetic markers contributing to narcolepsy onset in a 17-year-old female.
    Language English
    Publishing date 2024-03-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2177883-8
    ISSN 1744-313X ; 1744-3121
    ISSN (online) 1744-313X
    ISSN 1744-3121
    DOI 10.1111/iji.12666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Predicting flow cytometry crossmatch results from single-antigen bead testing.

    Flynn, Patrick A / Fernando, Sebastian / Worthington, Judith E / Poulton, Kay V

    International journal of immunogenetics

    2024  Volume 51, Issue 2, Page(s) 93–99

    Abstract: The aim of this study was to devise an algorithm that would predict flow cytometry crossmatch (FCXM) results using single-antigen bead (SAB) mean fluorescent intensity (MFI) levels using samples received through the National External Quality Assurance ... ...

    Abstract The aim of this study was to devise an algorithm that would predict flow cytometry crossmatch (FCXM) results using single-antigen bead (SAB) mean fluorescent intensity (MFI) levels using samples received through the National External Quality Assurance Scheme (NEQAS) 2B external proficiency testing scheme between 2019 and 2023. A total of 159 serum samples were retrospectively screened using LABScreen Single Antigen Class I and II (SAB), and 40 peripheral blood samples were human leucocyte antigen (HLA) typed with LABType SSO. Donor-specific antibodies were identified for each cell-serum combination tested, and cumulative MFI values were calculated for each test before correlating the screening result with the consensus crossmatch results for this scheme. HLA Class I MFIs were combined to predict the T cell crossmatch. For the B cell crossmatch prediction, two options were considered: (i) HLA Class II MFI values alone and (ii) HLA Class I + Class II MFIs. Receiver operating characteristic analysis was carried out to identify the combined MFI threshold that predicted NEQAS consensus results with the greatest sensitivity and specificity. HLA Class I combined MFI >5000 predicted T cell crossmatch results with 96% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 92% negative predictive value (NPV). For B cell results, HLA Class I + Class II combined MFIs >11,000 gave the best model, showing 97% sensitivity, 82% specificity, 96% PPV and 85% NPV. However, for samples with only HLA Class II sensitization, combined MFIs >13,000 improved the B cell crossmatch predictions: 92% sensitivity, 95% specificity, 96% PPV and 91% NPV. Using this model, combined MFI can be used to predict the immunological risk posed by donor-specific antibodies when it is not possible to carry out an FCXM.
    MeSH term(s) Humans ; Flow Cytometry/methods ; Kidney Transplantation ; Retrospective Studies ; Histocompatibility Testing/methods ; Antibodies ; HLA Antigens ; Isoantibodies ; Graft Rejection
    Chemical Substances Antibodies ; HLA Antigens ; Isoantibodies
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2177883-8
    ISSN 1744-313X ; 1744-3121
    ISSN (online) 1744-313X
    ISSN 1744-3121
    DOI 10.1111/iji.12658
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Immunology of cord blood T-cells favors augmented disease response during clinical pediatric stem cell transplantation for acute leukemia.

    Borrill, Roisin / Poulton, Kay / Wynn, Robert

    Frontiers in pediatrics

    2023  Volume 11, Page(s) 1232281

    Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) has been an important and efficacious treatment for acute leukemia in children for over 60 years. It works primarily through the graft-vs.-leukemia (GVL) effect, in which donor T-cells and other ... ...

    Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) has been an important and efficacious treatment for acute leukemia in children for over 60 years. It works primarily through the graft-vs.-leukemia (GVL) effect, in which donor T-cells and other immune cells act to eliminate residual leukemia. Cord blood is an alternative source of stem cells for transplantation, with distinct biological and immunological characteristics. Retrospective clinical studies report superior relapse rates with cord blood transplantation (CBT), when compared to other stem cell sources, particularly for patients with high-risk leukemia. Xenograft models also support the superiority of cord blood T-cells in eradicating malignancy, when compared to those derived from peripheral blood. Conversely, CBT has historically been associated with an increased risk of transplant-related mortality (TRM) and morbidity, particularly from infection. Here we discuss clinical aspects of CBT, the unique immunology of cord blood T-cells, their role in the GVL effect and future methods to maximize their utility in cellular therapies for leukemia, honing and harnessing their antitumor properties whilst managing the risks of TRM.
    Language English
    Publishing date 2023-09-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2023.1232281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SARS-CoV-2: An immunogenetics call to arms.

    Clark, Brendan / Poulton, Kay

    International journal of immunogenetics

    2020  Volume 47, Issue 4, Page(s) 319–323

    Abstract: Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing ... ...

    Abstract Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.
    MeSH term(s) Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/pathology ; Disease Susceptibility/immunology ; Humans ; Immunity, Innate/immunology ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances IL1B protein, human ; IL6 protein, human ; Interleukin-1beta ; Interleukin-6 ; TNF protein, human ; Tumor Necrosis Factor-alpha
    Keywords covid19
    Language English
    Publishing date 2020-07-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2177883-8
    ISSN 1744-313X ; 1744-3121
    ISSN (online) 1744-313X
    ISSN 1744-3121
    DOI 10.1111/iji.12504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Strategies for Success With Umbilical Cord Haematopoietic Stem Cell Transplantation in Children With Malignant and Non-Malignant Disease Indications.

    Wynn, Rob / Nataraj, Ramya / Nadaf, Rubiya / Poulton, Kay / Logan, Alison

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 836594

    Abstract: Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more ...

    Abstract Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more often HLA-mismatched compared to other unrelated donor transplants. The ability to transplant in such a setting, indeed without high rates of chronic Graft versus Host Disease (GVHD), constitutes an advantage compared to other unrelated donor cell sources and there are other advantages specifically associated with cord blood as a donor cell source. These advantages must be weighed against its disadvantage, and we have utilised cord blood preferentially as a donor cell source in certain clinical situations in paediatric medicine. In non-malignant diseases, outcomes in metabolic disease are critically dependent on age at transplant and the enzyme delivered by that transplant, and in cord blood transplantation then the time to transplant can be minimised and the engrafted recipients have higher chimerism that delivers higher enzyme levels. In malignant diseases, studies have described reduced relapse rate and better GVHD-free survival, and so we have prioritised cord as a donor cell source where the risk of relapse is highest, and the effects of higher transplant related mortality is most clearly offset by the reduced relapse rates.
    Language English
    Publishing date 2022-04-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.836594
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: SARS‐CoV‐2

    Clark, Brendan / Poulton, Kay

    International Journal of Immunogenetics

    An immunogenetics call to arms

    2020  Volume 47, Issue 4, Page(s) 319–323

    Keywords Genetics(clinical) ; Immunology ; Genetics ; Molecular Biology ; General Medicine ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2177883-8
    ISSN 1744-3121
    ISSN 1744-3121
    DOI 10.1111/iji.12504
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Strategies for Success With Umbilical Cord Haematopoietic Stem Cell Transplantation in Children With Malignant and Non-Malignant Disease Indications

    Rob Wynn / Ramya Nataraj / Rubiya Nadaf / Kay Poulton / Alison Logan

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more ...

    Abstract Umbilical Cord blood is an intuitively attractive stem cell source, but its use has declined since it is associated with an increased procedure-related morbidity and transplant related mortality. Some of this reflects that cord blood transplants are more often HLA-mismatched compared to other unrelated donor transplants. The ability to transplant in such a setting, indeed without high rates of chronic Graft versus Host Disease (GVHD), constitutes an advantage compared to other unrelated donor cell sources and there are other advantages specifically associated with cord blood as a donor cell source. These advantages must be weighed against its disadvantage, and we have utilised cord blood preferentially as a donor cell source in certain clinical situations in paediatric medicine. In non-malignant diseases, outcomes in metabolic disease are critically dependent on age at transplant and the enzyme delivered by that transplant, and in cord blood transplantation then the time to transplant can be minimised and the engrafted recipients have higher chimerism that delivers higher enzyme levels. In malignant diseases, studies have described reduced relapse rate and better GVHD-free survival, and so we have prioritised cord as a donor cell source where the risk of relapse is highest, and the effects of higher transplant related mortality is most clearly offset by the reduced relapse rates.
    Keywords leukaemia ; bone marrow transplant ; Hurler disease ; cord blood ; graft versus host disease ; immunotherapy ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: SARS-CoV-2: An immunogenetics call to arms

    Clark, Brendan / Poulton, Kay

    Int J Immunogenet

    Abstract: Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing ... ...

    Abstract Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #640248
    Database COVID19

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  9. Article ; Online: HLA expression levels of unstimulated and cytokine stimulated human umbilical vein endothelial cells.

    Carey, B Sean / Poulton, Kay V / Poles, Anthony

    HLA

    2020  Volume 95, Issue 6, Page(s) 505–515

    Abstract: Transplant rejection occurs following recipient recognition of mismatched HLA on donor tissue, but active rejection is dependent not only upon the severity of the T cell or alloantibody response, but also upon the cell surface expression of target HLA ... ...

    Abstract Transplant rejection occurs following recipient recognition of mismatched HLA on donor tissue, but active rejection is dependent not only upon the severity of the T cell or alloantibody response, but also upon the cell surface expression of target HLA molecules. To investigate the variation in HLA expression using a model of endothelium, human umbilical vein endothelial cell (HUVEC) cultures were generated from 48 umbilical cords donated consecutively following planned caesarean section. HUVECs were stimulated using the cytokines tumour necrosis factor alpha and interferon gamma and HLA expression of unstimulated and stimulated cells determined using flow cytometry. HLA-A2, HLA-A3 and HLA-C antigens all showed a modest increase in expression for 12 hours post cell activation, followed by a more pronounced response over the next 24 to 36 hours. Each of these antigens increased by up to 40 times over unstimulated levels and in addition cells homozygous for specific HLA antigens on average had twice the amount of antigen expressed compared with cells heterozygous for that antigen, both when unstimulated and following cytokine stimulation. Cell activation is an important consideration in the assessment of transplant risk and may help progress towards understanding why rejection does not always occur in the presence of significant donor specific antibody. This data also confirms guidelines for transplantation, which recommend doubling the specific antibody level when considering immunological risk for homozygous donors.
    MeSH term(s) Alleles ; Cells, Cultured ; Cytokines/pharmacology ; Endothelium, Vascular ; Female ; HLA Antigens/genetics ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Pregnancy
    Chemical Substances Cytokines ; HLA Antigens
    Language English
    Publishing date 2020-02-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.13808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: HLA-C expression level in both unstimulated and stimulated human umbilical vein endothelial cells is defined by allotype.

    Carey, B Sean / Poulton, Kay V / Poles, Anthony

    HLA

    2020  Volume 95, Issue 6, Page(s) 532–542

    Abstract: Human leukocyte antigens (HLA) are present on the surface of all nucleated cells, with the level of expression dependent on the particular HLA locus, the cell type and cellular activation state. Human umbilical vein endothelial cells (HUVECs) are easily ... ...

    Abstract Human leukocyte antigens (HLA) are present on the surface of all nucleated cells, with the level of expression dependent on the particular HLA locus, the cell type and cellular activation state. Human umbilical vein endothelial cells (HUVECs) are easily isolated from umbilical cords and may aid our understanding of HLA expression on the vascular endothelium in the setting of transplantation. Endothelial cells on the donor-recipient interface form the barrier between transplanted organs and the host immune system. Increased knowledge of the variation in levels of individual HLA specificities may inform the assessment of transplant risk. HUVECs from 48 full term babies born consecutively following planned caesarean section were isolated, HLA typed and grown on gelatin coated culture wells. Once confluent, cells were stimulated with optimal concentrations of the cytokines TNF-α and IFN-γ for 24 hours and HLA-C expression on both unstimulated and stimulated cells was quantified by flow cytometry using the fluorescent labelled monoclonal antibody DT-9 PE. Unstimulated HLA-C expression varied by over 60% between allotypes (ANOVA, P = .004). Following stimulation, HLA-C levels increased over 15-fold and showed the same variation of expression between allotypes (P < .001). Cell surface HLA-C expression increases between 500% and 3125%, after stimulation for 24 hours. HLA-C level varies between allotypes and cells expressing more HLA-C at baseline tended to have corresponding higher levels of HLA-C following cytokine stimulation (Pearson's correlation coefficient between unstimulated and stimulated expression, P = .002).
    MeSH term(s) Alleles ; Cells, Cultured ; Cesarean Section ; Female ; HLA-C Antigens/genetics ; Human Umbilical Vein Endothelial Cells ; Humans ; Pregnancy
    Chemical Substances HLA-C Antigens
    Language English
    Publishing date 2020-03-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.13852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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