The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients

被引:20
作者
Parsons, Ronald F. [1 ]
Zahid, Arslan [2 ]
Bumb, Shalini [3 ]
Decker, Hannah [2 ]
Sullivan, Harold C. [4 ]
Lee, Frances Eun-Hyung [5 ]
Badell, Idelberto Raul [1 ]
Ford, Mandy L. [1 ]
Larsen, Christian P. [1 ]
Pearson, Thomas C. [1 ]
Jackson, Annette M. [6 ]
Chen, Dong-Feng [7 ]
Levine, Matthew [8 ]
Kamoun, Malek [9 ]
Bray, Robert A. [4 ]
Gebel, Howard M. [4 ]
机构
[1] Emory Univ, Sch Med, Dept Surg, Div Transplantat, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Atlanta, GA USA
[3] Univ Cincinnati, Dept Internal Med, Cincinnati, OH USA
[4] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA
[5] Emory Univ, Sch Med, Dept Med, Div Pulm Allergy Crit Care & Sleep Med, Atlanta, GA USA
[6] Duke Univ, Sch Med, Dept Surg, Durham, NC USA
[7] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA
[8] Univ Penn, Dept Surg, Perelman Sch Med, Div Transplantat, Philadelphia, PA 19104 USA
[9] Univ Penn, Dept Pathol, Perelman Sch Med, Philadelphia, PA 19104 USA
关键词
alloantibody; clinical research; practice; immunosuppressant - fusion proteins and monoclonal antibodies; belatacept; immunosuppression; immune modulation; kidney transplantation; nephrology; sensitization; COSTIMULATION BLOCKADE; RENAL-TRANSPLANTATION; ALLOCATION SYSTEM; ANTIBODY; DESENSITIZATION; RESPONSES; CELLS; KAS;
D O I
10.1111/ajt.15585
中图分类号
R61 [外科手术学];
学科分类号
摘要
Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was >= 98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P < .0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P < .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.
引用
收藏
页码:573 / 581
页数:9
相关论文
共 28 条
[1]   Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway [J].
Adams, Andrew B. ;
Ford, Mandy L. ;
Larsen, Christian P. .
JOURNAL OF IMMUNOLOGY, 2016, 197 (06) :2045-2050
[2]   Single-Center Kidney Paired Donation: The Methodist San Antonio Experience [J].
Bingaman, A. W. ;
Wright, F. H., Jr. ;
Kapturczak, M. ;
Shen, L. ;
Vick, S. ;
Murphey, C. L. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2012, 12 (08) :2125-2132
[3]   Transplanting the highly sensitized patient: The emory algorithm [J].
Bray, R. A. ;
Nolen, J. D. L. ;
Larsen, C. ;
Pearson, T. ;
Newell, K. A. ;
Kokko, K. ;
Guasch, A. ;
Tso, P. ;
Mendel, J. B. ;
Gebel, H. M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2006, 6 (10) :2307-2315
[4]   De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies [J].
Bray, R. A. ;
Gebel, H. M. ;
Townsend, R. ;
Roberts, M. E. ;
Polinsky, M. ;
Yang, L. ;
Meier-Kriesche, H. -U. ;
Larsen, C. P. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2018, 18 (07) :1783-1789
[5]   Posttransplant reduction in preexisting donor-specific antibody levels after belatacept- versus cyclosporine-based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT-EXT [J].
Bray, R. A. ;
Gebel, H. M. ;
Townsend, R. ;
Roberts, M. E. ;
Polinsky, M. ;
Yang, L. ;
Meier-Kriesche, H. -U. ;
Larsen, C. P. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2018, 18 (07) :1774-1782
[6]   Dual targeting: Combining costimulation blockade and bortezomib to permit kidney transplantation in sensitized recipients [J].
Burghuber, Christopher K. ;
Manook, Miriam ;
Ezekian, Brian ;
Gibby, Adriana C. ;
Leopardi, Frank, V ;
Song, Minqing ;
Jenks, Jennifer ;
Saccoccio, Frances ;
Permar, Sallie ;
Farris, Alton B. ;
Iwakoshi, Neal N. ;
Kwun, Jean ;
Knechtlel, Stuart J. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2019, 19 (03) :724-736
[7]   Comparison of de novo IgM and IgG anti-HLA DSAs between belatacept- and calcineurin-treated patients: An analysis of the BENEFIT and BENEFIT-EXT trial cohorts [J].
Everly, Matthew J. ;
Roberts, Mustimbo ;
Townsend, Robert ;
Bray, Robert A. ;
Gebel, Howard M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2018, 18 (09) :2305-2313
[8]   Allocating Deceased Donor Kidneys to Candidates with High Panel-Reactive Antibodies [J].
Gebel, Howard M. ;
Kasiske, Bertram L. ;
Gustafson, Sally K. ;
Pyke, Joshua ;
Shteyn, Eugene ;
Israni, Ajay K. ;
Bray, Robert A. ;
Snyder, Jon J. ;
Friedewald, John J. ;
Segev, Dorry L. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2016, 11 (03) :505-511
[9]   Long-Lived Plasma Cells Are Contained within the CD19-CD38hiCD138+ Subset in Human Bone Marrow [J].
Halliley, Jessica L. ;
Tipton, Christopher M. ;
Liesveld, Jane ;
Rosenberg, Alexander F. ;
Darce, Jaime ;
Gregoretti, Ivan V. ;
Popova, Lana ;
Kaminiski, Denise ;
Fucile, Christopher F. ;
Albizua, Igor ;
Kyu, Shuya ;
Chiang, Kuang-Yueh ;
Bradley, Kyle T. ;
Burack, Richard ;
Slifka, Mark ;
Hammarlund, Erika ;
Wu, Hao ;
Zhao, Liping ;
Walsh, Edward E. ;
Falsey, Ann R. ;
Randall, Troy D. ;
Cheung, Wan Cheung ;
Sanz, Inaki ;
Lee, F. Eun-Hyung .
IMMUNITY, 2015, 43 (01) :132-145
[10]   Kidney exchange match rates in a large multicenter clearinghouse [J].
Holscher, Courtenay M. ;
Jackson, Kyle ;
Chow, Eric K. H. ;
Thomas, Alvin G. ;
Haugen, Christine E. ;
DiBrito, Sandra R. ;
Purcell, Carlin ;
Ronin, Matthew ;
Waterman, Amy D. ;
Wang, Jacqueline Garonzik ;
Massie, Allan B. ;
Gentry, Sommer E. ;
Segev, Dorry L. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2018, 18 (06) :1510-1517