Influence of Test Technique on Sensitization Status of Patients on the Kidney Transplant Waiting List

Abstract

The exquisitely sensitive single antigen bead (SAB) technique was shown to detect human leukocyte antigen (HLA) antibodies in sera of healthy male blood donors. Such false reactions can have an impact on critical decisions, especially with respect to the determination of unacceptable HLA-antigen mismatches in patients awaiting a kidney transplant. We tested pretransplant sera of 534 patients on the kidney waiting list using complement-dependent cytotoxicity (CDC), enzyme-linked immunosorbent assay (ELISA) and SAB in parallel. Evidence of HLA antibodies was obtained in 5% of patients using CDC, 14% using ELISA, and 81% using SAB. Among patients without history of an immunizing event, 77% showed evidence of HLA antibodies in SAB. In contrast 98% of these patients were negative in ELISA and CDC. In patients without an immunizing event, SAB-detected antibodies reacted not always weakly but with mean fluorescence intensity (MFI) values as high as 14 440. High-MFIvalue antibodies were found in some of these patients with HLA specificities that are rather common in general population, consideration of which would lead to unjustified exclusion of potential kidney donors. False SAB reactions can be unveiled by testing with additional antibody assays. Denial of donor kidneys to recipients based on HLA-antibody specificities detected exclusively in the SAB assay is not advisable.

Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants

“…Interpreting HLA or other antibodies as pathogenic requires expert opinion and is moving toward probabilistic assessment (28)(29)(30)(31), but this will often preclude the simple designation as ''positive versus negative'' specified in the Banff guidelines. For example, preexisting class I DSA has ABMR, antibody-mediated rejection; DSA, donor-specific antibody; NDSA, non-donor-specific HLA antibody.…”

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…The recent widespread application of SPA-based tests in clinical practice has confirmed the higher sensitivity of these diagnostic methods. Conflictingly, however, a growing number of studies in kidney transplantation patients have also shown that only a portion of Luminex-detectable HLA antibodies appear to cause antibody-mediated rejection [25][26][27]. This differentiation between clinically relevant and irrelevant DSAs is a major challenge, both before and after kidney [24,27,28].…”

“…Conflictingly, however, a growing number of studies in kidney transplantation patients have also shown that only a portion of Luminex-detectable HLA antibodies appear to cause antibody-mediated rejection [25][26][27]. This differentiation between clinically relevant and irrelevant DSAs is a major challenge, both before and after kidney [24,27,28]. For example, the pathogenetic roles of different Ig subclasses or those of complement-and non-complement-fixing DSAs in antibody-mediated rejection are controversially discussed [29].…”

Persistent immune-tolerance to non-inherited maternal antigen (NIMA) allows successful kidney transplantation in regraft patient: Case report

“…The significance of the DQ antibodies is increasingly recognized following the introduction of the SAB assay which considered today to be the most sensitive and specific method for alloimmunization assessment [13][14][15]. However, it is becoming clear that the detection of the HLA antibodies by SAB is not absolutely perfect due to the variation in densities and orientations of the antigen coated beads [16][17][18]. HLA-DQ antigen consists of two (αβ) polymorphic chains [19].…”