Erik Berglund1,2, Mette Andersen Ljungdahl1, Darko Bogdanović1, David Berglund3, Jonas Wadström1, Jan Kowalski4, Gerald Brandacher5, Dorota Kamińska6, Christina L Kaufman7, Simon G Talbot8, Kodi Azari9, Luis Landin10, Christoph Höhnke11,12, Karen M Dwyer13, Pedro C Cavadas14, Alessandro Thione14, Brendan Clarke15, Simon Kay15, Dan Wilks15, Subramania Iyer16, Martin Iglesias17, Ömer Özkan18, Özlenen Özkan18, Johanna Krapf19, Annemarie Weissenbacher20,21, Palmina Petruzzo22, Stefan Schneeberger20. 1. Division of Transplantation Surgery, Department of Transplantation Surgery, CLINTEC, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. 2. Department of Medicine, Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY. 3. Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Sweden. 4. JK Biostatistics AB, Stockholm, Sweden. 5. Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. 6. Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland. 7. Christine M. Kleinert Institute for Hand and Microsurgery, Louisville, KY. 8. Division of Plastic Surgery, Brigham and Women's Hospital, Boston, MA. 9. Division of Plastic Surgery, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. 10. FIBHULP/IdiPaz, Division of Plastic and Reconstructive Surgery, Hospital Universitario "La Paz," Madrid, Spain. 11. Division of Plastic and Reconstructive Surgery, Klinikum Memmingen, Memmingen, Germany. 12. Technical University Munich, München, Germany. 13. School of Medicine, Faculty of Health, Deakin University, Geelong, Australia. 14. Plastic and Reconstructive Surgery Division, Clinica Cavadas, Valencia, Spain. 15. Department of Plastic and Reconstructive Surgery, Leeds General Infirmary, Leeds, United Kingdom. 16. Plastic/Reconstructive Surgery, Amrita Institute of Medical sciences, Kochi, Kerala, India. 17. Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico. 18. Department of Plastic and Reconstructive Surgery, Akdeniz University Faculty of Medicine, Antalya, Turkey. 19. Department of Plastic and Reconstructive Surgery, Innsbruck Medical University, Innsbruck, Austria. 20. Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria. 21. Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, Oxford University, Oxford, United Kingdom. 22. Department of Transplantation, Hôpital Edouard Herriot, HCL, Lyon, France.
Abstract
BACKGROUND: Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. METHODS: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. RESULTS: Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. CONCLUSIONS: While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
BACKGROUND:Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. METHODS: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. RESULTS: Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. CONCLUSIONS: While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
Authors: Flemming Puscz; Mehran Dadras; Alexander Dermietzel; Frank Jacobsen; Marcus Lehnhardt; Björn Behr; Tobias Hirsch; Maximilian Kueckelhaus Journal: PLoS One Date: 2020-06-26 Impact factor: 3.240
Authors: Joseph Y Kim; Zhengdeng Lei; Mark Maienschein-Cline; George E Chlipala; Arumugam Balamurugan; Sue V McDiarmid; Kodi Azari; Otto O Yang Journal: Transplantation Date: 2021-07-01 Impact factor: 5.385
Authors: Theresa Hautz; Franka Messner; Annemarie Weissenbacher; Hubert Hackl; Martin Kumnig; Marina Ninkovic; Valeria Berchtold; Johanna Krapf; Bettina G Zelger; Bernhard Zelger; Dolores Wolfram; Gerhard Pierer; Wolfgang N Löscher; Robert Zimmermann; Markus Gabl; Rohit Arora; Gerald Brandacher; Raimund Margreiter; Dietmar Öfner; Stefan Schneeberger Journal: Transpl Int Date: 2020-11-10 Impact factor: 3.842