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Journal articles on the topic 'Donor-specific antiboy'

Author: Grafiati

Published: 4 June 2021

Last updated: 18 February 2022

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1

Tinckam, Kathryn J., and Peter S. Heeger. "Complementing donor-specific antibody testing." Nature Reviews Nephrology 9, no. 12 (November 5, 2013): 713–14. http://dx.doi.org/10.1038/nrneph.2013.234.

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2

Mcmillan, M. A., J. D. Briggs, B. J. R. Junor, R. N. M. Macsween, and G. P. Sandilands. "DONOR-SPECIFIC TRANSFUSION AND ANTIBODY RESPONSE." Lancet 329, no. 8535 (March 1987): 744–45. http://dx.doi.org/10.1016/s0140-6736(87)90382-5.

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3

Book, B. K., N. G. Higgins, G. J. Eckert, K. M. Rosner, A. Lobashevsky, and M. D. Pescovitz. "DONOR SPECIFIC ANTIBODY CHANGES AFTER NEPHRECTOMY." Transplantation Journal 90 (July 2010): 378. http://dx.doi.org/10.1097/00007890-201007272-00697.

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4

Zhang, Rubin. "Donor-Specific Antibodies in Kidney Transplant Recipients." Clinical Journal of the American Society of Nephrology 13, no. 1 (April 26, 2017): 182–92. http://dx.doi.org/10.2215/cjn.00700117.

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Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. De novo donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient’s immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.

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5

Habig, Dennis F., Justine L. Gaspari, Parvez M. Lokhandwala, Ronald E. Domen, Catherine S. Abendroth, Zakiyah Kadry, Nasrollah Ghahramani, Riaz Ali Shah, Ashokkumar Jain, and Hiroko Shike. "Donor-specific antibody to trans-encoded donor HLA-DQ heterodimer." Human Immunology 76, no. 8 (August 2015): 587–90. http://dx.doi.org/10.1016/j.humimm.2015.09.004.

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6

Everly, M. J., J. J. Everly, B. Susskind, P. Brailey, L. J. Arend, R. R. Alloway, P. Roy-Chaudhury, et al. "Proteasome Inhibition Reduces Donor-Specific Antibody Levels." Transplantation Proceedings 41, no. 1 (January 2009): 105–7. http://dx.doi.org/10.1016/j.transproceed.2008.10.073.

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7

Matsumoto, Cal, Jason Hawksworth, Alexander H. Kroemer, Raffaele GIrlanda, Nada Yazgi, Khalid Khan, Stuart S. Kaufman, et al. "Denovo Donor Specific Antibody in Intestinal Transplantation." Transplantation 101 (June 2017): S5. http://dx.doi.org/10.1097/01.tp.0000521279.38245.2d.

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8

Hawksworth, Jason S., and Cal S. Matsumoto. "Donor-specific antibody management in intestine transplantation." Current Opinion in Organ Transplantation 24, no. 2 (April 2019): 212–18. http://dx.doi.org/10.1097/mot.0000000000000619.

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9

Schwaiger, Elisabeth, Farsad Eskandary, Nicolas Kozakowski, Gregor Bond, Željko Kikić, Daniel Yoo, Susanne Rasoul-Rockenschaub, Rainer Oberbauer, and Georg A. Böhmig. "Deceased donor kidney transplantation across donor-specific antibody barriers: predictors of antibody-mediated rejection." Nephrology Dialysis Transplantation 31, no. 8 (March 24, 2016): 1342–51. http://dx.doi.org/10.1093/ndt/gfw027.

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10

Ma, Jeffrey, Anita Patel, and Kathryn Tinckam. "Donor-Specific Antibody Monitoring: Where Is the Beef?" Advances in Chronic Kidney Disease 23, no. 5 (September 2016): 317–25. http://dx.doi.org/10.1053/j.ackd.2016.08.004.

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11

Mamatov, E., A. F. Kocaay, M. A. Koc, Z. K. Celebi, S. Sengül, K. Keven, H. Tutkak, and A. Tuzuner. "Predictive Role of Neutrophil Gelatinase–Associated Lipocaline in Donor-Specific Antibody–Positive and Donor-Specific Antibody–Negative Renal Transplant Patients." Transplantation Proceedings 47, no. 6 (July 2015): 1688–91. http://dx.doi.org/10.1016/j.transproceed.2015.06.010.

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12

Higgins, R., D. Briggs, D. Lowe, M. Hathaway, R. Hamer, N. Krishnan, and D. Zehnder. "CHANGES IN DONOR SPECIFIC AND THIRD PARTY HLA ANTIBODY LEVELS AFTER ANTIBODY INCOMPATIBLE TRANSPLANTATION; PRODUCTION, ABSORPTION AND DONOR-SPECIFIC MODULATION." Transplantation 86, Supplement (July 2008): 46. http://dx.doi.org/10.1097/01.tp.0000332672.58940.4f.

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13

Hayde, Nicole, Yi Bao, James Pullman, Bin Ye, R. Brent Calder, Monica Chung, Daniel Schwartz, et al. "The Clinical and Genomic Significance of Donor-Specific Antibody–Positive/C4d-Negative and Donor-Specific Antibody–Negative/C4d-Negative Transplant Glomerulopathy." Clinical Journal of the American Society of Nephrology 8, no. 12 (September 12, 2013): 2141–48. http://dx.doi.org/10.2215/cjn.04240413.

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14

Lee, Boram, Soomin Ahn, Haeryoung Kim, Ho-Seong Han, Yoo-Seok Yoon, Jai Young Cho, and Young Rok Choi. "Donor Specific Antibody Negative Antibody-Mediated Rejection after ABO Incompatible Liver Transplantation." Journal of the Korean Society for Transplantation 32, no. 4 (2018): 108. http://dx.doi.org/10.4285/jkstn.2018.32.4.108.

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15

Jordan, Stanley C., Suphamai Bunnapradist, Jonathan S. Bromberg, Anthony J. Langone, David Hiller, James P. Yee, John J. Sninsky, Robert N. Woodward, and Arthur J. Matas. "Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients." Transplantation Direct 4, no. 9 (September 2018): e379. http://dx.doi.org/10.1097/txd.0000000000000821.

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16

Aikawa, A., T. Hadano, T. Ohara, M. Yamashita, K. Arai, N. Hirayama, Y. Mori, M. Muramatsu, and A. Hasegawa. "Donor specific antibody suppression in ABO incompatible kidney transplantation." Transplantation Proceedings 33, no. 1-2 (February 2001): 395–97. http://dx.doi.org/10.1016/s0041-1345(00)02063-7.

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17

Piazza, A., L. Borrelli, P. I. Monaco, E. Poggi, F. Pisani, M. Valeri, D. Fraboni, S. Servetti, C. U. Casciani, and D. Adorno. "Posttransplant donor-specific antibody characterization and kidney graft survival." Transplant International 13, S1 (June 2000): S439—S443. http://dx.doi.org/10.1111/j.1432-2277.2000.tb02078.x.

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18

Pereira, Shalini, Susan Perkins, Jar-How Lee, Wayne Shumway, William LeFor, Mayra Lopez-Cepero, Cynthia Wong, Amy Connolly, Jane C. Tan, and F. Carl Grumet. "Donor-specific antibody against denatured HLA-A1: Clinically nonsignificant?" Human Immunology 72, no. 6 (June 2011): 492–98. http://dx.doi.org/10.1016/j.humimm.2011.02.012.

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19

Hawksworth, Jason, Ahmed M. Elsabbagh, Sandra Rosen-Bronson, Raffaele Girlanda, Alexander Kroemer, Stuart Kaufman, Khalid Khan, et al. "Sensitization and Preformed Donor Specific Antibody in Intestinal Transplantation." Transplantation 101 (June 2017): S1. http://dx.doi.org/10.1097/tp.0000000000001799.

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20

Chhatwani, L., J. Mooney, R. Balestra, R. Lee, C. Lou, D. Weill, D. Tyan, and G. Dhillon. "Complement-Fixing Donor-Specific Antibody and Lung Transplant Outcomes." Journal of Heart and Lung Transplantation 33, no. 4 (April 2014): S160. http://dx.doi.org/10.1016/j.healun.2014.01.430.

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21

Adams, Patrick W., Julie Graziani, Charles Orosz, and Andrea A. Zachary. "A donor-specific Elisa for monitoring antibody down-regulation." Human Immunology 64, no. 10 (October 2003): S119. http://dx.doi.org/10.1016/j.humimm.2003.08.223.

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22

Jain, Anil, Prabir Roy-Chaudhury, Michael Cardi, E. Steve Woodle, Michael Hanaway, Joseph Austin, Shaoming Huang, Paul Brailey, Ramkrishnan Manohar, and Brian M. Susskind. "Donor-specific antibody detection correlates with late humoral rejection." Human Immunology 65, no. 9-10 (September 2004): S63. http://dx.doi.org/10.1016/j.humimm.2004.07.118.

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23

Stamm, Luz, Anastasio Salazar, Iwona Galaszkiewicz, and Noureddine Berka. "Up regulation of non donor specific antibody after transplantation." Human Immunology 66, no. 8 (August 2005): 15. http://dx.doi.org/10.1016/j.humimm.2005.08.023.

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24

Park, Younhee, Hyon-Suk Kim, Dong Il Won, Hae Jin Kim, and Yu Seun Kim. "52-P: Correlations of donor-specific antibody detection methods." Human Immunology 70 (November 2009): S37. http://dx.doi.org/10.1016/j.humimm.2009.09.085.

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25

Allan, Lenka, and Paul A. Keown. "P240 Unmasking prozone, detecting the hidden donor specific antibody." Human Immunology 78 (September 2017): 230. http://dx.doi.org/10.1016/j.humimm.2017.06.300.

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26

Piazza, A., L. Borrelli, P. I. Monaco, E. Poggi, F. Pisani, M. Valeri, D. Fraboni, S. Servetti, C. U. Casciani, and D. Adorno. "Posttransplant donor-specific antibody characterization and kidney graft survival." Transplant International 13 (April 28, 2000): S439—S443. http://dx.doi.org/10.1007/s001470050378.

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27

Matsumoto, Cal S., and Sandra Rosen-Bronson. "Donor-specific antibody and sensitized patients in intestinal transplantation." Current Opinion in Organ Transplantation 26, no. 2 (January 29, 2021): 245–49. http://dx.doi.org/10.1097/mot.0000000000000853.

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28

Onda, Shinji, Hiroaki Shiba, Kenei Furukawa, Takashi Horiuchi, Yoshihiro Shirai, Jungo Yasuda, Hironori Shiozaki, Takeshi Gocho, Yuichi Ishida, and Katsuhiko Yanaga. "SUCCESSFUL LIVING-DONOR LIVER TRANSPLANTATION FOR DONOR-SPECIFIC ANTIBODY-POSITIVE RECIPIENTS USING RITUXIMAB." Transplantation 104, S3 (September 2020): S473. http://dx.doi.org/10.1097/01.tp.0000701032.00779.44.

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29

Ziemann, Malte, Wolfgang Altermann, Katharina Angert, Wolfgang Arns, Anette Bachmann, Tamam Bakchoul, Bernhard Banas, et al. "Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation." Clinical Journal of the American Society of Nephrology 14, no. 7 (June 18, 2019): 1056–66. http://dx.doi.org/10.2215/cjn.13401118.

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Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.ResultsPretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.ConclusionsPreformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.

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30

Roux, A., I. Bendib Le Lan, S. Holifanjaniaina, K. A. Thomas, A. M. Hamid, C. Picard, D. Grenet, et al. "Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics." American Journal of Transplantation 16, no. 4 (February 4, 2016): 1216–28. http://dx.doi.org/10.1111/ajt.13589.

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31

Lan, James H., Matthew Kadatz, Doris T. Chang, Jagbir Gill, Howard M. Gebel, and John S. Gill. "Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival." Clinical Journal of the American Society of Nephrology 16, no. 2 (January 25, 2021): 275–83. http://dx.doi.org/10.2215/cjn.13640820.

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Background and objectivesPanel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies.Design, setting, participants, & measurementsRetrospective observational study of kidney allograft survival among 4058 zero HLA-A–, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci.ResultsAmong 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%–97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss: hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients.ConclusionsCalculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3

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32

Kanter Berga, J., A. Sancho Calabuig, E. Gavela Martinez, N. Puig Alcaraz, A. Avila Bernabeu, J. Crespo Albiach, P. Molina Vila, S. Beltrán Catalan, and L. Pallardó Mateu. "Desensitization Protocol in Recipients of Deceased Kidney Donor With Donor-Specific Antibody–Low Titers." Transplantation Proceedings 48, no. 9 (November 2016): 2880–83. http://dx.doi.org/10.1016/j.transproceed.2016.07.050.

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33

Costa, Luciano J., Omar Moussa, Robert A. Bray, and Robert K. Stuart. "Overcoming HLA-DPB1 donor specific antibody-mediated haematopoietic graft failure." British Journal of Haematology 151, no. 1 (July 16, 2010): 94–96. http://dx.doi.org/10.1111/j.1365-2141.2010.08305.x.

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34

Njue, Faith, and Sharon Chih. "When to intervene for donor-specific antibody after heart transplantation." Current Opinion in Organ Transplantation 24, no. 3 (June 2019): 271–78. http://dx.doi.org/10.1097/mot.0000000000000634.

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35

Mulley, W. R., L. Cantwell, F. Hudson, L. Huang, R. Holdsworth, S. Cohney, and J. Kanellis. "UNMASKING DONOR SPECIFIC ANTIBODIES IN PATIENTS WITH ANTIBODY MEDIATED REJECTION." Transplantation Journal 90 (July 2010): 271. http://dx.doi.org/10.1097/00007890-201007272-00513.

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36

Zito, Anna, Antonio Schena, Giuseppe Grandaliano, Loreto Gesualdo, and Francesco Paolo Schena. "Increasing relevance of donor-specific antibodies in antibody-mediated rejection." Journal of Nephrology 26, no. 2 (December 20, 2012): 237–42. http://dx.doi.org/10.5301/jn.5000240.

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37

Clerkin, K. J., S. W. Restaino, E. R. Vasilescu, E. Zorn, C. C. Marboe, and D. M. Mancini. "The Impact of Donor Specific Antibodies on Antibody Mediated Rejection." Journal of Heart and Lung Transplantation 35, no. 4 (April 2016): S207. http://dx.doi.org/10.1016/j.healun.2016.01.582.

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38

Steele, Melissa, Christina L. Kaufman, Rosemary Ouseph, Allan M. Ramirez, Tuna Ozyurekoglu, Christopher M. Jones, and Tiffany K. Roberts. "P031 Role of donor specific antibody (DSA) in hand transplantation." Human Immunology 78 (September 2017): 76. http://dx.doi.org/10.1016/j.humimm.2017.06.091.

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39

Reddy, Dheera, Danielle Ladie, Robert C. Scott, Partick Yang, and Harold C. Yang. "P110 Clinical predictors of donor specific antibody following kidney transplantation." Human Immunology 79 (October 2018): 143. http://dx.doi.org/10.1016/j.humimm.2018.07.168.

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40

Lefaucheur, Carmen, Denis Viglietti, Carol Bentlejewski, Jean-Paul Duong van Huyen, Dewi Vernerey, Olivier Aubert, Jérôme Verine, et al. "IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury." Journal of the American Society of Nephrology 27, no. 1 (August 20, 2015): 293–304. http://dx.doi.org/10.1681/asn.2014111120.

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41

Zhao, Daqiang, Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, and Qiquan Sun. "Triptolide inhibits donor-specific antibody production and attenuates mixed antibody-mediated renal allograft injury." American Journal of Transplantation 18, no. 5 (December 29, 2017): 1083–95. http://dx.doi.org/10.1111/ajt.14602.

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42

Gjelaj, C., A. Luke, A. Paschenko, R. Fletcher, E. Borukhov, D. Nnani, D. B. Sims, et al. "Sum Total MFI of Donor-Specific Antibody - A Prognostic Marker in Antibody-Mediated Rejection." Journal of Heart and Lung Transplantation 39, no. 4 (April 2020): S243. http://dx.doi.org/10.1016/j.healun.2020.01.921.

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43

Roux, A., I. Lelan Bendib, S. Holifanjaniaina, K. Thomas, C. Picard, D. Grenet, S. De Miranda, et al. "Association of Anti DQ Donor Specific Antibody with Antibody Mediated Rejection in Lung Transplantation." Journal of Heart and Lung Transplantation 35, no. 4 (April 2016): S134. http://dx.doi.org/10.1016/j.healun.2016.01.366.

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44

Linjama, T., R. Niittyvuopio, J. Tuimala, M. Pyörälä, H. Rintala, J. Rimpiläinen, M. Kauppila, J. Peräsaari, and E. Juvonen. "Platelet donor selection for HLA-immunised patients; the impact of donor-specific HLA antibody levels." Transfusion Medicine 27, no. 5 (April 6, 2017): 375–83. http://dx.doi.org/10.1111/tme.12412.

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45

Knight, R. J., S. J. Patel, K. Achkar, G. Land, S. Dilioglou, J. Hamilton, P. Barretto, and A. O. Gaber. "A GRADED DESENSITIZATION TREATMENT PROTOCOL FOR MANAGEMENT OF LIVING DONOR RECIPIENTS WITH DONOR SPECIFIC ANTIBODY." Transplantation Journal 90 (July 2010): 85. http://dx.doi.org/10.1097/00007890-201007272-00162.

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46

Yoshizawa, A., H. Egawa, Y. Ogura, K. Yurugi, R. Hishida, E. Ashihara, A. Miyagawa-Hayashino, et al. "THE IMPACT OF DONOR SPECIFIC ANTIBODY ON LIVER ALLOGRAFT SURVIVAL AFTER LIVING DONOR LIVER TRANSPLANTATION." Transplantation Journal 90 (July 2010): 376. http://dx.doi.org/10.1097/00007890-201007272-00694.

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47

Boiko, Julie R., Bita Sahaf, and David B. Miklos. "Allotype Reagents Distinguish Donor and Recipient Antibodies after Hematopoietic Transplantation." Blood 108, no. 11 (November 16, 2006): 2906. http://dx.doi.org/10.1182/blood.v108.11.2906.2906.

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Abstract Allogeneic immune responses provide beneficial graft-versus-leukemia (GVL) and detrimental graft-versus-host disease (GVHD). To characterize allogeneic B cells and their antibodies in relation to GVHD and GVL, antigen specific assays are required to distinguish donor and recipient antibodies. Inherited polymorphisms in heavy chain constant regions of immunoglobulin can be recognized by allotype specific monoclonal antibodies. We hypothesize that B cell reconstitution differs after myeloablative and nonmyeloablative (NMA) HCT with clinical implications. To test this, we developed allotype ELISAs to quantify donor and recipient antibody responses for specific infectious and allogeneic antigens. Human sera were screened by ELISA coating monoclonal antibodies specific for human allotypes (IgG1m(f), m(z), m(a), IgG2m(n), and IgG3m(g1)) at titers providing shared dynamic ranges. Pre-transplant sera from 48 patients and their donors were serially diluted, and allotype-specific immunoglobulin was detected by alkaline phosphatase-conjugated polyclonal anti-human IgG. Allotype-null sera clearly segregated from wild-type sera with 10-fold absorbency differences. Each null phenotype was confirmed by total IgG and isotype-specific quantification. Overall, IgG1m(f) was null in 8 of 96 sera (null allele frequency 29%), and IgG2m(n) was null in 23 of 96 (null allele frequency 48%). Six patients were null for both, and overall 17 of 48 donor/recipient transplant pairs were informative for either allotype. Nulls for the remaining three allotypes were infrequently recognized limiting their clinical utility. Additionally, we measured monoclonal IgG1 purified from 5 multiple myeloma patients identifying three null alleles, one wild-type, and a single intermediate polymorphism. Labeled conjugation of the wild-type monoclonal IgG1 enables competitive inhibition analysis of null allotype improving null allotype sensitivity for engraftment less than 5%. Sera were collected monthly from all HCT patients informative for allotype antibody. Three NMA HCT patients who underwent total lymphoid irradiation and anti-thymoglobulin (TLI/ATG) conditioning have donors that are null for IgG2m(n) and are being prospectively assessed for recipient antibody loss. Their recipient allotype-specific IgG persists at pretransplant recipient levels in all three patients measured six months after NMA HCT, and the lead patient expresses 100% pretransplant recipient allotype antibody ten months after HCT. Conversely, a single NMA patient null for IgG2m(n) with a wild-type donor has no detectable IgG2m(n) donor antibodies four months after HCT despite having 100% donor peripheral B cell engraftment measured 30 days after NMA HCT. In contrast, an informative patient undergoing myeloablative HCT developed 25% IgG2m(n) donor specific antibodies 3 months post-transplant, and 50% at 7 months. Others have reported donor allotype specific antibody achieves full engraftment by 6 months after myeloablative HCT (Van Tol et al. Blood 1996). Our ongoing preliminary studies suggest NMA HCT patients experience delayed donor antibody onset and prolonged recipient antibodies as compared to patients undergoing myeloablative HCT. In order to confirm this, we are measuring antigen-specific donor allotype antibody reconstitution for infectious antigens (EBV and tetanus) and allogeneic H-Y antigens.

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Summers, Phillip J., Aaron T. Whiteley, and Lee Ann Baxter-Lowe. "50-P: Comparison of Donor Specific Antibody Analysis Techniques: Maximum, Average, and Allele Specific." Human Immunology 71 (September 2010): S52. http://dx.doi.org/10.1016/j.humimm.2010.06.098.

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49

Krishnan, Nithya S., Daniel Zehnder, Sunil Daga, Dave Lowe, F. T. Lam, Habib Kashi, Lam Chin Tan, et al. "Behaviour of Non-Donor Specific Antibodies during Rapid Re-Synthesis of Donor Specific HLA Antibodies after Antibody Incompatible Renal Transplantation." PLoS ONE 8, no. 7 (July 26, 2013): e68663. http://dx.doi.org/10.1371/journal.pone.0068663.

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Kwun, Jean, Marie Matignon, Miriam Manook, Soulef Guendouz, Vincent Audard, David Kheav, Elsa Poullot, et al. "Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use." Journal of the American Society of Nephrology 30, no. 7 (June 21, 2019): 1206–19. http://dx.doi.org/10.1681/asn.2018121254.

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Abstract:

BackgroundDonor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production.MethodsTo target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant.ResultsThe animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P<0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; P<0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell–mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access.ConclusionsTargeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.

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