Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation

During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mecha...

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Main Authors: M. Kueht, P. Jindra, H.L. Stevenson, T.N. Galvan, B. Murthy, J. Goss, J. Anton, R. Abbas, M.F. Cusick
Format: Article
Language:English
Published: Elsevier 2021-03-01
Series:Molecular Genetics and Metabolism Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214426920301518
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spelling doaj-3d1867eefb694791b611bb8d5cc4856e2021-02-13T04:24:48ZengElsevierMolecular Genetics and Metabolism Reports2214-42692021-03-0126100705Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantationM. Kueht0P. Jindra1H.L. Stevenson2T.N. Galvan3B. Murthy4J. Goss5J. Anton6R. Abbas7M.F. Cusick8Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States of America; Correspondence to: M Kueht, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0533, United States of America.Department of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of AmericaDepartment of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States of AmericaDepartment of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of AmericaDepartment of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of AmericaDepartment of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of AmericaDepartment of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of AmericaDepartment of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of AmericaDepartment of Pathology, University of Michigan Medicine, 2800 Plymouth Rd., Building 36, Ann Arbor, MI 48109, United States of America; Correspondence to: M F. Cusick, University of Michigan Medicine, 2800 Plymouth Rd., Building 36, Ann Arbor, MI 48109, United States of America.During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mechanisms and timing underlying immunologic changes that occur intra-operatively remain largely unknown. Therefore, we measured the intra- and peri-operative kinetics of anti-HLA antibodies in highly sensitized SLK recipients. In this study, pre- and post-operative blood samples were obtained from sensitized SLK candidates with documented DSA. Intra-operative samples were obtained from a sub-group of SLK recipients. Pretransplant anti-HLA antibody profiles were created and flow cytometry and anti-human globulin complement-dependent cytotoxic crossmatches were performed. Significant reductions in anti-HLA class I and II DSA were seen intra-operatively shortly after reperfusion of the liver allograft. This effect was most pronounced for anti-HLA class I DSA (mean change, −85%, p < 0.05); changes to anti-HLA class II DSA were less robust (mean change, −47%, p = 0.15). Importantly, non-DSA anti-HLA antibodies remained unchanged throughout the perioperative period, suggesting the mechanism(s) by which the liver lowers DSA levels are specific to the DSA. These data demonstrate the immunologic benefit of performing SLK is lasting and occurs very shortly after liver reperfusion.http://www.sciencedirect.com/science/article/pii/S2214426920301518Simultaneous liver-kidney transplantDonor specific antibodySensitized
collection DOAJ
language English
format Article
sources DOAJ
author M. Kueht
P. Jindra
H.L. Stevenson
T.N. Galvan
B. Murthy
J. Goss
J. Anton
R. Abbas
M.F. Cusick
spellingShingle M. Kueht
P. Jindra
H.L. Stevenson
T.N. Galvan
B. Murthy
J. Goss
J. Anton
R. Abbas
M.F. Cusick
Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation
Molecular Genetics and Metabolism Reports
Simultaneous liver-kidney transplant
Donor specific antibody
Sensitized
author_facet M. Kueht
P. Jindra
H.L. Stevenson
T.N. Galvan
B. Murthy
J. Goss
J. Anton
R. Abbas
M.F. Cusick
author_sort M. Kueht
title Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation
title_short Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation
title_full Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation
title_fullStr Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation
title_full_unstemmed Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation
title_sort intra-operative kinetics of anti-hla antibody in simultaneous liver-kidney transplantation
publisher Elsevier
series Molecular Genetics and Metabolism Reports
issn 2214-4269
publishDate 2021-03-01
description During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mechanisms and timing underlying immunologic changes that occur intra-operatively remain largely unknown. Therefore, we measured the intra- and peri-operative kinetics of anti-HLA antibodies in highly sensitized SLK recipients. In this study, pre- and post-operative blood samples were obtained from sensitized SLK candidates with documented DSA. Intra-operative samples were obtained from a sub-group of SLK recipients. Pretransplant anti-HLA antibody profiles were created and flow cytometry and anti-human globulin complement-dependent cytotoxic crossmatches were performed. Significant reductions in anti-HLA class I and II DSA were seen intra-operatively shortly after reperfusion of the liver allograft. This effect was most pronounced for anti-HLA class I DSA (mean change, −85%, p < 0.05); changes to anti-HLA class II DSA were less robust (mean change, −47%, p = 0.15). Importantly, non-DSA anti-HLA antibodies remained unchanged throughout the perioperative period, suggesting the mechanism(s) by which the liver lowers DSA levels are specific to the DSA. These data demonstrate the immunologic benefit of performing SLK is lasting and occurs very shortly after liver reperfusion.
topic Simultaneous liver-kidney transplant
Donor specific antibody
Sensitized
url http://www.sciencedirect.com/science/article/pii/S2214426920301518
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