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  1. Article ; Online: A modeling approach for mean fluorescence intensity value harmonization and cutoff prediction for luminex single antigen bead assays of two different vendors.

    Karahan, Gonca E / Haasnoot, Geert W / Voogt-Bakker, Kim / Claas, Frans H J / Roelen, Dave / Heidt, Sebastiaan

    HLA

    2023  Volume 102, Issue 5, Page(s) 557–569

    Abstract: Luminex single antigen bead (SAB) kits from One Lambda (OL) and Lifecodes (LC) are widely used for HLA antibody detection but have substantial differences in design and assay protocol resulting in different mean fluorescence intensity (MFI) values. Here, ...

    Abstract Luminex single antigen bead (SAB) kits from One Lambda (OL) and Lifecodes (LC) are widely used for HLA antibody detection but have substantial differences in design and assay protocol resulting in different mean fluorescence intensity (MFI) values. Here, we present a non-linear modeling approach to accurately convert MFI values between two vendors and to establish user-independent MFI cutoffs when analyzing big datasets. HLA antibody data from a total of 47 EDTA-treated sera tested using both OL and LC SAB kits were analyzed. MFI comparisons were made for the common 84 HLA class I and 63 class II beads. In the exploration set (n = 24), a non-linear hyperbola model on raw MFI corrected by locus-specific highest self MFI subtraction yielded the highest correlation (class I r
    MeSH term(s) Humans ; HLA Antigens ; Alleles ; Antibodies ; Histocompatibility Testing/methods ; Kidney Transplantation/methods ; Isoantibodies ; Graft Rejection
    Chemical Substances HLA Antigens ; Antibodies ; Isoantibodies
    Language English
    Publishing date 2023-05-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.15082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 661: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Antibody verification of HLA class I and class II eplets by human monoclonal HLA antibodies.

    Kramer, Cynthia S M / Bezstarosti, Suzanne / Franke-van Dijk, Marry E I / Vergunst, Manon / Roelen, Dave L / Uyar-Mercankaya, Merve / Voogt-Bakker, Kim H / Heidt, Sebastiaan

    HLA

    2024  Volume 103, Issue 1, Page(s) e15345

    Abstract: In solid organ transplantation, formation of de novo donor-specific HLA antibodies is induced by mismatched eplets on donor HLA molecules. While several studies have shown a strong correlation between the number of eplet mismatches and inferior outcomes, ...

    Abstract In solid organ transplantation, formation of de novo donor-specific HLA antibodies is induced by mismatched eplets on donor HLA molecules. While several studies have shown a strong correlation between the number of eplet mismatches and inferior outcomes, not every eplet mismatch is immunogenic. Eplets are theoretically defined entities, necessitating formal proof that they can be recognised and bound by antibodies. This antibody verification is pivotal to ensure that clinically relevant eplets are considered in studies on molecular matching. Recombinant human HLA-specific monoclonal antibodies (mAbs) were generated from HLA-reactive B cell clones isolated from HLA immunised individuals using recombinant HLA molecules. Subsequently, the reactivity patterns of the mAbs obtained from single antigen bead assay were analysed using HLA-EMMA software to identify single or configurations of solvent accessible amino acids uniquely present on the reactive HLA alleles and were mapped to eplets. Two HLA class I and seven HLA class II-specific human mAbs were generated from four individuals. Extensive mAb reactivity analysis, led to antibody verification of three HLA-DR-specific eplets, and conversion of five eplets (one HLA-A, one HLA-B, two HLA-DR, and one HLA-DP), from provisionally verified to truly antibody-verified. Finally, one HLA-DQ-specific eplet was upgraded from level A2 to level A1 verification evidence. The generation of recombinant human HLA-specific mAbs with different specificities contributes significantly to the antibody verification of eplets and therefore is instrumental for implementation of eplet matching in the clinical setting.
    MeSH term(s) Humans ; Antibodies, Monoclonal ; Epitopes ; Alleles ; HLA-DR Antigens ; Tissue Donors ; HLA-B Antigens ; HLA Antigens ; Histocompatibility Testing ; Graft Rejection
    Chemical Substances Antibodies, Monoclonal ; Epitopes ; HLA-DR Antigens ; HLA-B Antigens ; HLA Antigens
    Language English
    Publishing date 2024-01-18
    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.15345
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 661: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: HLA-DQ eplet mismatch load may identify kidney transplant patients eligible for tacrolimus withdrawal without donor-specific antibody formation after mesenchymal stromal cell therapy.

    Bezstarosti, Suzanne / Meziyerh, Soufian / Reinders, Marlies E J / Voogt-Bakker, Kim / Groeneweg, Koen E / Roelen, Dave L / Kers, Jesper / de Fijter, Johan W / Heidt, Sebastiaan

    HLA

    2023  Volume 102, Issue 1, Page(s) 3–12

    Abstract: Recently, the randomized phase-II Triton study demonstrated that mesenchymal stromal cell (MSC) therapy facilitated early tacrolimus withdrawal in living donor kidney transplant recipients. The current sub-study analyzed formation of de novo donor- ... ...

    Abstract Recently, the randomized phase-II Triton study demonstrated that mesenchymal stromal cell (MSC) therapy facilitated early tacrolimus withdrawal in living donor kidney transplant recipients. The current sub-study analyzed formation of de novo donor-specific HLA antibodies (dnDSA) in the context of the degree of HLA eplet mismatches. At the time of protocol biopsy at 6 months, 7/29 patients (24%) in the MSC group and 1/27 patient (3.7%) in the control group had developed dnDSA. In the MSC group, all dnDSA were anti-HLA-DQ; two patients had anti-DQ alone and five patients combined with anti-class I, HLA-DR or -DP. Despite excess dnDSA formation in the MSC-arm of the study, the evolution of eGFR (CKD-EPI) and proteinuria were comparable 2 years posttransplant. All dnDSA were complement-binding and three patients had antibody-mediated rejection in the protocol biopsy, but overall rejection episodes were not increased. Everolimus had to be discontinued in nine patients because of toxicity, and tacrolimus was reintroduced in six patients because of dnDSA formation. The HLA-DQ eplet mismatch load independently associated with dnDSA (adjusted hazard ratio = 1.07 per eplet mismatch, p = 0.008). A threshold of ≥11 HLA-DQ eplet mismatches predicted subsequent dnDSA in all 11 patients in the MSC group, but specificity was low (44%). Further research is warranted to explore HLA molecular mismatch load as a biomarker to guide personalized maintenance immunosuppression in kidney transplantation.
    MeSH term(s) Humans ; Kidney Transplantation/adverse effects ; Tacrolimus/therapeutic use ; Antibody Formation ; Graft Rejection ; Histocompatibility Testing/methods ; Alleles ; Antibodies ; HLA Antigens/genetics
    Chemical Substances Tacrolimus (WM0HAQ4WNM) ; Antibodies ; HLA Antigens
    Language English
    Publishing date 2023-03-03
    Publishing country England
    Document type Clinical Trial, Phase II ; Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2845111-9
    ISSN 2059-2310 ; 2059-2302
    ISSN (online) 2059-2310
    ISSN 2059-2302
    DOI 10.1111/tan.15008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 661: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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