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Xenoreactive antibodies and latent fibrin formation in VAD and cardiac transplant recipients can confound the detection and measurement of anti‐ AT 1R antibodies
Author(s) -
Oaks Martin,
Michel Karen,
Downey Francis X.,
Thohan Vinay
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14753
Subject(s) - antibody , medicine , autoantibody , transplantation , immunology , angiotensin ii , heart transplantation , receptor , antigen
Autoantibodies to the angiotensin II type 1 receptor ( AT 1R) are thought to be important in antibody‐mediated rejection ( AMR ), especially in the absence of anti‐ HLA antibodies. We used a variety of methods to examine the specificity of a commercially available kit designed to quantitate anti‐ AT 1R antibodies. We found that fibrin formation in serum samples from patients awaiting cardiac transplantation with ventricular assist devices ( VADs ) can produce falsely elevated anti‐ AT 1R values. In addition, absorption studies with a variety of cell lines with or without expression of human AT 1R, and those that express xenoantigens, suggest that many of the antibodies detected in the AT 1R test system are heterophilic and have reactivity to xenoantigens. Furthermore, we provide data that show that reactivity to the sialic acid Neu5Gc is a common finding among samples that are highest in anti‐ AT 1R levels. We conclude that a common laboratory method for quantitation of anti‐ AT 1R antibodies is nonspecific and overestimates the frequency of true positives. A reevaluation of the role that anti‐ AT 1R antibodies play in allograft function and patient outcomes is warranted.