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Gül-Klein S, Hegermann H, Röhle R, et al. Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies. J Inflamm Res. 2021;14:2697-2712doi: 10.2147/JIR.S307778.
Gül-Klein, S., Hegermann, H., Röhle, R., Schmelzle, M., Tacke, F., Schöning, W., Öllinger, R., Dziodzio, T., Maier, P., Plewe, J. M., Horst, D., Sauer, I. M., Pratschke, J., Lachmann, N., & Eurich, D. (2021). Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies. Journal of inflammation research, 142697-2712. https://doi.org/10.2147/JIR.S307778
Gül-Klein, Safak, et al. "Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies." Journal of inflammation research vol. 14 (2021): 2697-2712. doi: https://doi.org/10.2147/JIR.S307778
Gül-Klein S, Hegermann H, Röhle R, Schmelzle M, Tacke F, Schöning W, Öllinger R, Dziodzio T, Maier P, Plewe JM, Horst D, Sauer IM, Pratschke J, Lachmann N, Eurich D. Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies. J Inflamm Res. 2021 Jun 23;14:2697-2712. doi: 10.2147/JIR.S307778. eCollection 2021. PMID: 34188517; PMCID: PMC8236257.
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J Inflamm Res. 2021 Jun 23;14:2697-2712. doi: 10.2147/JIR.S307778. eCollection 2021.

Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies.

Journal of inflammation research

Safak Gül-Klein, Henriette Hegermann, Robert Röhle, Moritz Schmelzle, Frank Tacke, Wenzel Schöning, Robert Öllinger, Tomasz Dziodzio, Patrick Maier, Julius M Plewe, David Horst, Igor Maximilian Sauer, Johann Pratschke, Nils Lachmann, Dennis Eurich

Affiliations

  1. Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany.
  2. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany.
  3. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Coordinating Center for Clinical Studies, Berlin, Germany.
  4. Berlin Institute of Health (BIH), Berlin, Germany.
  5. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Hepatology & Gastroenterology, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany.
  6. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  7. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, HLA Laboratory, Institute of Transfusion Medicine, Histocompatibility and Immunogenetics, Charité - Universitätsmedizin, Berlin, Germany.

PMID: 34188517 PMCID: PMC8236257 DOI: 10.2147/JIR.S307778

Abstract

BACKGROUND: Donor-specific antibodies (DSA) against donor human leukocyte antigen after liver transplantation, which are associated with histological changes, have been widely studied with respect to their sustained impact on transplant function. However, their long-term impact after liver transplantation remains unclear.

METHODS: We performed a cross-sectional analysis from June 2016 to July 2017 that included all patients who presented themselves for scheduled follow-up after receiving a liver transplantation between September 1989 and December 2016. In addition to a liver protocol biopsy, patients were screened for human leukocyte antigen antibodies (HLAab) and donor-specific antibodies. Subsequently, the association between human leukocyte antigen antibodies, donor-specific antibodies, histologic and clinical features, and immunosuppression was analyzed.

RESULTS: Analysis for human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was performed for 291 and 271 patients. A significant association between higher inflammation grades and the presence of human leukocyte antigen antibodies and donor-specific antibodies was detected, while fibrosis stages remained unaffected. These results were confirmed by multivariate logistic regression for inflammation showing a significant increase for presence of human leukocyte antigen antibodies and donor-specific antibodies (OR: 4.43; 95% CI: 1.67-12.6; p=0.0035). Furthermore, the use of everolimus in combination with tacrolimus was significantly associated with the status of negative human leukocyte antigen antibodies and donor-specific antibodies. Viral etiology for liver disease, hepatocellular carcinoma (HCC) and higher steatosis grades of the graft were significantly associated with a lower rate of human leukocyte antigen antibodies. The impact of human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was associated with higher levels of laboratory parameters, such as transaminases and bilirubin.

CONCLUSION: Donor-specific antibodies against donor human leukocyte antigen are associated with histological and biochemical graft inflammation after liver transplantation, while fibrosis seems to be unaffected. Future studies should validate these findings for longer observation periods and specific subgroups.

© 2021 Gül-Klein et al.

Keywords: donor-specific antibodies; human leukocyte antigen antibodies; liver biopsy; liver transplantation

Conflict of interest statement

Professor Moritz Schmelzle reports personal fees from Merck Serono, Bayer, non-financial support from ERBE, Amgen, non-financial support from Johnson & Johnson, Takeda, Olympus, Medtronic, Intuitive,

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