Development and Validation of a Multiplex Non-HLA Antibody Assay for the Screening of Kidney Transplant Recipients

被引：34

作者：

Kamburova, Elena G. ^{[1
]}

Kardol-Hoefnagel, Tineke ^{[1
]}

Wisse, Bram W. ^{[1
]}

Joosten, Irma ^{[2
]}

Allebes, Wil A. ^{[2
]}

van der Meer, Arnold ^{[2
]}

Hilbrands, Luuk B. ^{[3
]}

Baas, Marije C. ^{[3
]}

Spierings, Eric ^{[1
]}

Hack, Cornelis E. ^{[1
]}

van Reekum, Franka E. ^{[4
]}

van Zuilen, Arjan D. ^{[4
]}

Verhaar, Marianne C. ^{[4
]}

Bots, Michiel L. ^{[5
]}

Drop, Adriaan C. A. D. ^{[1
]}

Plaisier, Loes ^{[1
]}

Meeldijk, Jan ^{[1
]}

Bovenschen, Niels ^{[1
,6
]}

Seelen, Marc A. J. ^{[7
]}

Sanders, Jan Stephan ^{[7
]}

Hepkema, Bouke G. ^{[8
]}

Lambeck, Annechien J. A. ^{[8
]}

Bungener, Laura B. ^{[8
]}

Roozendaal, Caroline ^{[8
]}

Tilanus, Marcel G. J. ^{[9
]}

Voorter, Christina E. ^{[9
]}

Wieten, Lotte ^{[9
]}

van Duijnhoven, Elly M. ^{[10
]}

Gelens, Marielle A. C. J. ^{[10
]}

Christiaans, Maarten H. L. ^{[10
]}

van Ittersum, Frans J. ^{[11
]}

Nurmohamed, Shaikh A. ^{[11
]}

Lardy, Neubury M. ^{[12
]}

Swelsen, Wendy ^{[12
]}

van der Pant, Karlijn A. M. I. ^{[13
]}

van der Weerd, Neelke C. ^{[13
]}

ten Berge, Ineke J. M. ^{[13
]}

Bemelman, Frederike J. ^{[13
]}

van der Boog, Paul J. M. ^{[14
]}

de Fijter, Johan W. ^{[14
]}

Betjes, Michiel G. H. ^{[15
]}

Heidt, Sebastiaan ^{[16
]}

Roelen, Dave L. ^{[16
]}

Claas, Frans H. ^{[16
]}

Otten, Henny G. ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Lab Med Immunol,Lab Med, Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Nephrol, Nijmegen, Netherlands

[4] Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, Netherlands

[5] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[6] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[7] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands

[8] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands

[9] Maastricht Univ, Med Ctr, Dept Transplantat Immunol, Tissue Typing Lab, Maastricht, Netherlands

[10] Maastricht Univ, Div Nephrol, Dept Internal Med, Med Ctr, Maastricht, Netherlands

[11] Vrije Univ Amsterdam, Dept Nephrol, Amsterdam Univ Med Ctr, Amsterdam, Netherlands

[12] Sanquin Diagnost Serv, Dept Immunogenet, Amsterdam, Netherlands

[13] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Internal Med, Renal Transplant Unit, Amsterdam, Netherlands

[14] Leiden Univ, Dept Nephrol, Med Ctr, Leiden, Netherlands

[15] Erasmus MC, Nephrol, Dept Internal Med, Rotterdam, Netherlands

[16] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

关键词：

non-HLA antibody; kidney transplant; Luminex; multiplex assay; protein production; HaloTag; II TYPE-1 RECEPTOR; CROSS-MATCH TEST; MEDIATED REJECTION; RISK; ANTIGENS; IDENTIFICATION; TARGETS;

D O I：

10.3389/fimmu.2018.03002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The best treatment for patients with end-stage renal disease is kidney transplantation. Although graft survival rates have improved in the last decades, patients still may lose their grafts partly due to the detrimental effects of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) and to a lesser extent also by antibodies directed against non-HLA antigens expressed on the donor endothelium. Assays to detect anti-HLA antibodies are already in use for many years and have been proven useful for transplant risk stratification. Currently, there is a need for assays to additionally detect multiple non-HLA antibodies simultaneously in order to study their clinical relevance in solid organ transplantation. This study describes the development, technical details and validation of a high-throughput multiplex assay for the detection of antibodies against 14 non-HLA antigens coupled directly to MagPlex microspheres or indirectly via a HaloTag. The non-HLA antigens have been selected based on a literature search in patients with kidney disease or following transplantation. Due to the flexibility of the assay, this approach can be used to include alternative antigens and can also be used for screening of other organ transplant recipients, such as heart and lung.

引用

页数：12

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