Detection of HLA Donor-Specific Antibodies with Screening and/or Specificity Kits and Antibody-Mediated Rejection in Kidney Transplant Recipients

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Abstract

Background

Detection of HLA donor-specific antibodies (DSA) with solid phase multiplex-bead arrays has been significant but imperfectly associated with antibody-mediated rejection (AMR) in kidney transplant (KT) recipients. Nowadays to assess the presence of DSA, Luminex panels manufactured kits are used for screening and single antigen beads (SAB) for determining the specificity. The high cost of SAB limits their general use. In many laboratories SAB are only used if screening is positive. We aimed to evaluate if SAB only performed when screening is positive (strategy1) fails to identify relevant DSA detected by direct SAB (strategy2).

Methods

Kidney transplant recipients with post-transplant biopsies (2011-2015) and serum for DSA evaluation were recruited. We compared validity of both strategies in DSA detection.

Results

118 KT recipients with one biopsy each; 16 normal biopsies (N), 53 with AMR and 49 with Interstitial Fibrosis and Tubular Atrophy (IFTA). Figure 1 shows the prevalence of DSA in the groups with both strategies. There were no differences in sensitivity (60.3% vs. 77.3%, p=0.08) or specificity (92.3% vs. 87.7%; p=0.44) between strategy 1 and 2. Significant differences were found in positive (86.5% vs. 83.6%; p=0.01) and negative (74% vs. 82.6%; p=0.02) predictive values.

Results

Strategy 2 detected DSA in 15 cases missed by screening. Among them, 1 had N biopsy, 4 IFTA and 10 AMR (with 3 graft-losses).

Conclusions

The evaluation of anti-HLA antibodies with direct SAB increased the detection of DSA in 17% cases of AMR and 17% without AMR missed by using SAB after screening+. It seems advisable to use directly SAB for DSA studies in case of possible AMR. Further studies are needed to assess cost-benefit analysis.

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