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Review
. 2022 May 6:13:864671.
doi: 10.3389/fimmu.2022.864671. eCollection 2022.

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

Rosa G M Lammerts  1 , Dania Altulea  2 , Bouke G Hepkema  1 , Jan-Stephan Sanders  2 , Jacob van den Born  2 , Stefan P Berger  2
Affiliations
Review

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

Rosa G M Lammerts et al. Front Immunol. .

Abstract

To date, human leukocyte antigens (HLA) have been the major focus in the approach to acute and chronic antibody-mediated rejection (AMBR) in solid-organ transplantation. However, evidence from the clinic and published studies has shown that non-HLA antibodies, particularly anti-endothelial cell antibodies (AECAs), are found either in the context of AMBR or synergistically in the presence of donor-specific anti-HLA antibodies (DSA). Numerous studies have explored the influence of AECAs on clinical outcomes, yet the determination of the exact clinical relevance of non-HLA antibodies in organ transplantation is not fully established. This is due to highly heterogeneous study designs including differences in testing methods and outcome measures. Efforts to develop reliable and sensitive diagnostic non-HLA antibody tests are continuously made. This is essential considering the technical difficulties of non-HLA antibody assays and the large variation in reported incidences of antibodies. In addition, it is important to take donor specificity into account in order to draw clinically relevant conclusions from non-HLA antibody assays. Here, we provide an overview of non-HLA solid-phase and cell-based crossmatch assays for use in solid-organ transplantation that are currently available, either in a research setting or commercially.

Keywords: antibody-mediated allograft rejection; endothelial crossmatching assays; non-HLA; solid-organ transplantation; solid-phase detection assays.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Non-HLA immunization can both contribute to and arise from allograft injury. (Non-HLA antibodies depicted in the illustration are examples, and no scientific evidence exists that it is this specific antibody that is present at this time point). Created with biorender.com.
Figure 2
Figure 2
Assays for alloreactive antibodies. Abs, antibodies; ELISA, enzyme-linked immunosorbent assay; HLA, human leukocyte antigen. * New/unknown non-HLA Abs. Created with biorender.com.
Figure 3
Figure 3
Summary points.
See this image and copyright information in PMC

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