Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens
IntroductionThe development of de novo anti-HLA donor specific antibodies (DSAs) is associated with poor outcomes in kidney transplant recipients. It is surmised that an interaction between DSAs and the graft endothelium cause tissue injury, however, the exact underlying pathomechanism and optimal m...
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1407407/full |
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| author | Linda Lóczi Linda Lóczi Réka P. Szabó Rita Orbán-Kálmándi Rebeka Hodossy-Takács Anikó Szilvási Zoltán Szalai Gábor Nagy Péter Antal-Szalmás Balázs Nemes Zsuzsa Bagoly Zsuzsa Bagoly Zsuzsa Bagoly |
| author_facet | Linda Lóczi Linda Lóczi Réka P. Szabó Rita Orbán-Kálmándi Rebeka Hodossy-Takács Anikó Szilvási Zoltán Szalai Gábor Nagy Péter Antal-Szalmás Balázs Nemes Zsuzsa Bagoly Zsuzsa Bagoly Zsuzsa Bagoly |
| author_sort | Linda Lóczi |
| collection | DOAJ |
| description | IntroductionThe development of de novo anti-HLA donor specific antibodies (DSAs) is associated with poor outcomes in kidney transplant recipients. It is surmised that an interaction between DSAs and the graft endothelium cause tissue injury, however, the exact underlying pathomechanism and optimal management of patients with DSAs remain undetermined.AimsWe hypothesized that in kidney transplant recipients the presence of DSAs induce hemostasis alterations, including hypercoagulability, as assessed by the thrombin generation assay (TGA). Patients and methods. In this observational cohort study, 27 kidney transplant recipients with DSAs (DSA+ group) and 16 without DSAs (DSA– group) were enrolled. Venous blood samples were obtained, and besides routine laboratory tests, von Willebrand factor antigen (VWF), FVIII activity, soluble E selectin (sEsel), soluble P selectin (sPsel), TGA, clot lysis assay (CLA), complement levels (C3, C4) were measured. To correlate results with potential changes in DSA status over time, patients were followed and reassessed 6 ± 1.5 months later.ResultsVWF and sPsel did not differ between groups, but both parameters were increased in the majority of patients. Endogenous thrombin potential (ETP) was significantly higher in the DSA+ group as compared to DSA– patients (median:1666; IQR:1438-2012 vs. 1230; IQR:1097-1659 nM*min, p=0.0019). Follow-up measurements indicated that the observed hemostasis alterations were not transient. CLA parameters, C3 and C4 did not differ between DSA+ and DSA– groups. The extent of anti-HLA II DSA positivity correlated positively with ETP, while tacrolimus levels negatively correlated with ETP and VWF/FVIII levels.ConclusionsIn patients with anti-HLA class II DSAs, thrombin generation was significantly increased as compared to DSA– kidney transplant recipients, suggesting that the presence of antibodies is associated with hypercoagulability. Tacrolimus levels were negatively associated with TGA parameters. Hypercoagulability, associated with the presence of DSAs, may potentially contribute to the pathomechanism of antibody-mediated graft injury, warranting future prospective studies. |
| format | Article |
| id | doaj-art-980b1d6c772a4aa8947cc7d4641752f8 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-980b1d6c772a4aa8947cc7d4641752f82025-08-20T02:11:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14074071407407Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigensLinda Lóczi0Linda Lóczi1Réka P. Szabó2Rita Orbán-Kálmándi3Rebeka Hodossy-Takács4Anikó Szilvási5Zoltán Szalai6Gábor Nagy7Péter Antal-Szalmás8Balázs Nemes9Zsuzsa Bagoly10Zsuzsa Bagoly11Zsuzsa Bagoly12Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of Debrecen, Debrecen, HungaryHungarian Research Network-University of Debrecen (HUN-REN-DE) Cerebrovascular Research Group, Debrecen, HungaryDivision of Nephrology, Department of Internal Medicine, University of Debrecen, Debrecen, HungaryDivision of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of Debrecen, Debrecen, HungaryDivision of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of Debrecen, Debrecen, HungaryTransplantation Immunogenetics Laboratory, Hungarian National Blood Transfusion Service, Budapest, HungaryDivision of Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDivision of Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDivision of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of Debrecen, Debrecen, HungaryHungarian Research Network-University of Debrecen (HUN-REN-DE) Cerebrovascular Research Group, Debrecen, HungaryHungarian Academy of Sciences-University of Debrecen (MTA-DE) Lendület “Momentum” Hemostasis and Stroke Research Group, Debrecen, HungaryIntroductionThe development of de novo anti-HLA donor specific antibodies (DSAs) is associated with poor outcomes in kidney transplant recipients. It is surmised that an interaction between DSAs and the graft endothelium cause tissue injury, however, the exact underlying pathomechanism and optimal management of patients with DSAs remain undetermined.AimsWe hypothesized that in kidney transplant recipients the presence of DSAs induce hemostasis alterations, including hypercoagulability, as assessed by the thrombin generation assay (TGA). Patients and methods. In this observational cohort study, 27 kidney transplant recipients with DSAs (DSA+ group) and 16 without DSAs (DSA– group) were enrolled. Venous blood samples were obtained, and besides routine laboratory tests, von Willebrand factor antigen (VWF), FVIII activity, soluble E selectin (sEsel), soluble P selectin (sPsel), TGA, clot lysis assay (CLA), complement levels (C3, C4) were measured. To correlate results with potential changes in DSA status over time, patients were followed and reassessed 6 ± 1.5 months later.ResultsVWF and sPsel did not differ between groups, but both parameters were increased in the majority of patients. Endogenous thrombin potential (ETP) was significantly higher in the DSA+ group as compared to DSA– patients (median:1666; IQR:1438-2012 vs. 1230; IQR:1097-1659 nM*min, p=0.0019). Follow-up measurements indicated that the observed hemostasis alterations were not transient. CLA parameters, C3 and C4 did not differ between DSA+ and DSA– groups. The extent of anti-HLA II DSA positivity correlated positively with ETP, while tacrolimus levels negatively correlated with ETP and VWF/FVIII levels.ConclusionsIn patients with anti-HLA class II DSAs, thrombin generation was significantly increased as compared to DSA– kidney transplant recipients, suggesting that the presence of antibodies is associated with hypercoagulability. Tacrolimus levels were negatively associated with TGA parameters. Hypercoagulability, associated with the presence of DSAs, may potentially contribute to the pathomechanism of antibody-mediated graft injury, warranting future prospective studies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1407407/fullantibody-mediated rejectiondonor specific antibodykidney transplantationthrombin generationhemostasis |
| spellingShingle | Linda Lóczi Linda Lóczi Réka P. Szabó Rita Orbán-Kálmándi Rebeka Hodossy-Takács Anikó Szilvási Zoltán Szalai Gábor Nagy Péter Antal-Szalmás Balázs Nemes Zsuzsa Bagoly Zsuzsa Bagoly Zsuzsa Bagoly Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens Frontiers in Immunology antibody-mediated rejection donor specific antibody kidney transplantation thrombin generation hemostasis |
| title | Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens |
| title_full | Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens |
| title_fullStr | Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens |
| title_full_unstemmed | Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens |
| title_short | Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens |
| title_sort | increased thrombin generation in kidney transplant recipients with donor specific antibodies directed against human leukocyte antigens |
| topic | antibody-mediated rejection donor specific antibody kidney transplantation thrombin generation hemostasis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1407407/full |
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