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Clinical Significance of Alloantibodies in Hand Transplantation

A Multicenter Study

Berglund, Erik MD, PhD1,2; Andersen Ljungdahl, Mette MD1; Bogdanović, Darko MD1; Berglund, David MD, PhD3; Wadström, Jonas MD, PhD1; Kowalski, Jan4; Brandacher, Gerald MD5; Kamińska, Dorota MD, PhD6; Kaufman, Christina L. PhD7; Talbot, Simon G. MD8; Azari, Kodi MD9; Landin, Luis MD, PhD10; Höhnke, Christoph MD, PhD11,12; Dwyer, Karen M. PhD13; Cavadas, Pedro C. MD, PhD14; Thione, Alessandro MD, PhD14; Clarke, Brendan15; Kay, Simon MD15; Wilks, Dan MD15; Iyer, Subramania MD16; Iglesias, Martin MD17; Özkan, Ömer MD18; Özkan, Özlenen MD18; Krapf, Johanna MD19; Weissenbacher, Annemarie MD20,21; Petruzzo, Palmina MD, PhD22; Schneeberger, Stefan MD20

doi: 10.1097/TP.0000000000002650
Original Clinical Science–General
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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.

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.

Received 12 September 2018. Revision received 4 January 2019.

Accepted 17 January 2019.

The study was supported by Emil and Vera Cornell’s Foundation, Stig and Gunborg Westman’s Foundation, The Foundation Blanceflor Boncompagni Ludovisi née Bildt, the Hirsch Fellowship for Surgeons, Erik and Edith Fernström´s Foundation for Medical Research, and the Swedish Society of Medicine.

The authors declare no conflicts of interest.

E.B., M.A.L., D.B., D.B., J.W., A.W., P.P., and S.S. participated in research design, performing of the research, data analysis, and writing of the article. J.K., G.B., D.K., C.L.K., S.G.T., K.A., L.L., C.H., K.M.D., P.C.C., A.T., B.C., S.K., D.W., S.I., M.I., Ö.Ö., Ö.Ö., and J.K. all contributed to data analysis, performance of the research, and writing of the article.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Erik Berglund, MD, PhD, Division of Transplantation Surgery, Department of Transplantation Surgery, CLINTEC, Karolinska Institute, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. (Erik.Berglund@ki.se).

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