Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside

被引：30

作者：

Butler, Carrie L. ^{[1
]}

Hickey, Michelle J. ^{[1
]}

Jiang, Ning ^{[2
]}

Zheng, Ying ^{[1
]}

Gjertson, David ^{[1
]}

Zhang, Qiuheng ^{[1
]}

Rao, Ping ^{[1
]}

Fishbein, Gregory A. ^{[1
]}

Cadeiras, Martin ^{[3
]}

Deng, Mario C. ^{[3
]}

Banchs, Hector L. ^{[4
,5
]}

Torre, Guillermo ^{[6
]}

DeNofrio, David ^{[7
]}

Eisen, Howard J. ^{[8
]}

Kobashigawa, Jon ^{[9
]}

Starling, Randall C. ^{[10
]}

Kfoury, Abdallah ^{[11
]}

Van Bakel, Adrian ^{[12
]}

Ewald, Gregory ^{[13
]}

Balazs, Ivan ^{[2
]}

Baas, Arnold S. ^{[3
]}

Cruz, Daniel ^{[3
]}

Ardehali, Reza ^{[3
]}

Biniwale, Reshma ^{[3
]}

Kwon, Murray ^{[3
]}

Ardehali, Abbas ^{[3
]}

Nsair, Ali ^{[3
]}

Ray, Bryan ^{[2
]}

Reed, Elaine F. ^{[1
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[2] Immucor Inc, Norcross, GA USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA

[4] Cardiovasc Ctr Puerto Rico, Carolina, PR USA

[5] Caribbean Transplant Program, Carolina, PR USA

[6] Houston Methodist Hosp, Res Inst, Houston, TX 77030 USA

[7] Tufts Med Ctr, Boston, MA 02111 USA

[8] Drexel Univ, Coll Med, Philadelphia, PA USA

[9] Cedars Sinai Heart Inst, Los Angeles, CA USA

[10] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA

[11] Intermt Med Ctr, Salt Lake City, UT USA

[12] Med Univ South Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA

[13] Washington Univ, Dept Med, St Louis, MO USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2020年 / 20卷 / 10期

关键词：

autoantibody; autoantigen; clinical research; practice; heart transplantation; cardiology; histocompatibility; immunogenetics; microarray; protein array; organ transplantation in general; rejection; translational research; science; ENDOTHELIAL-CELL ANTIBODIES; CORONARY-ARTERY-DISEASE; MEDIATED REJECTION; HEART-TRANSPLANTATION; MICA ANTIBODIES; TARGETS; AUTOANTIBODIES; EXPRESSION; CLASSIFICATION; VASCULOPATHY;

D O I：

10.1111/ajt.15863

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

引用

页码：2768 / 2780

页数：13

共 22 条

[21] Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients
Lefaucheur, Carmen
Viglietti, Denis
Bouatou, Yassine
Philippe, Aurelie
Pievani, Daniele
Aubert, Olivier
Jean-Paul Duong Van Huyen
Taupin, Jean-Luc
Glotz, Denis
Legendre, Christophe
Loupy, Alexandre
Halloran, Philip F.
Dragun, Duska
KIDNEY INTERNATIONAL, 2019, 96 (01) : 189 - 201
[22] Non-HLA Antibodies: Angiotensin II Type 1 Receptor (Anti-AT1R) and Endothelin-1 Type A Receptor (Anti-ETAR) Are Associated With Renal Allograft Injury and Graft Loss
Banasik, M.
Boratynska, M.
Koscielska-Kasprzak, K.
Kaminska, D.
Zmonarski, S.
Mazanowska, O.
Krajewska, M.
Bartoszek, D.
Zabinska, M.
Myszka, M.
Kaminska, M.
Halon, A.
Dawiskiba, T.
Szyber, P.
Sas, A.
Klinger, M.
TRANSPLANTATION PROCEEDINGS, 2014, 46 (08) : 2618 - 2621

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