Sensitive Solid-Phase Detection of Donor-Specific Antibodies as an Aid Highly Relevant to Improving Allograft Outcomes
- PDF / 662,155 Bytes
- 17 Pages / 595.276 x 790.866 pts Page_size
- 36 Downloads / 155 Views
REVIEW ARTICLE
Sensitive Solid-Phase Detection of Donor-Specific Antibodies as an Aid Highly Relevant to Improving Allograft Outcomes Gerald Schlaf • Beatrix Pollok-Kopp Wolfgang W. Altermann
•
Ó Springer International Publishing Switzerland 2013
Abstract Transplant recipients who have had sensitizing events such as pregnancies, blood transfusions and previous transplants often develop antibodies directed against human leukocyte antigen (HLA)-molecules of the donor tissue. These pre-formed donor-specific antibodies (DSA) represent a high risk of organ failure as a consequence of antibody-mediated hyper-acute or acute allograft rejection. As a first assay to detect DSA, the complement-dependent lymphocytotoxicity assay (CDC) was established more than 40 years ago. However, this assay is characterized by several drawbacks such as a low sensitivity and a high susceptibility to various artificial factors generally not leading to valid and reliable outcomes under several circumstances that are reviewed in this article. Furthermore, only those antibodies that exert complement-fixing activity are detected. As a consequence, novel procedures that act independently of the complement system and that do not represent functional assays were generated in the format of solid phase assays (SPAs) (bead- or ELISA-based). In this article, we review the pros and cons of these sensitive SPA in comparison with the detection of DSA through the use of the traditional methods such as CDC and flow cytometric analyses. Potential drawbacks of the alternative methodological approaches comprising high background reactivity, susceptibility to environmental factors and the possible
G. Schlaf (&) W. W. Altermann Tissue Typing Laboratory, University Hospital Halle/Saale, Martin-Luther University of Halle-Wittenberg, Magdeburger Strasse 16, 06112 Halle (Saale), Germany e-mail: [email protected] B. Pollok-Kopp Department of Transfusion Medicine, University Hospital Go¨ttingen, Robert-Koch-Strasse 40, 37075 Go¨ttingen, Germany e-mail: [email protected]
influence of subjective operators’ errors concerning the interpretation of the results are summarized and critically discussed for each method. We provide a forecast on the future role of SPAs reliably excluding highly deleterious DSA, thus leading to an improved graft survival.
1 Introduction It has been known for more than 40 years that antibodies that are directed against human leukocyte antigens (HLAs) represent the dominant reason for hyper-acute or acute rejections of renal allografts and allografts of other organs [1–3]. These donor-specific anti-HLA antibodies (DSA) are thus regarded as a contraindication for grafting according to the transplantation guidelines of most countries and supranational societies (e.g. Eurotransplant Foundation) responsible for the supervision of the allocation of kidneys and other solid organs. Consequently, a so-called crossmatch (XM-) procedure was developed in the late 1960s in order to detect antibodies in a given recipient’s serum a
Data Loading...