False-positive reactivity of anti-human leukocyte antigen antibodies detected using the single-antigen bead assay

Hum Immunol. 2021 Jun;82(6):409-413. doi: 10.1016/j.humimm.2021.03.002. Epub 2021 Apr 17.

Abstract

The single-antigen bead assay (SABA) demonstrates high sensitivity and specificity for detecting anti-human leukocyte antigen (HLA) antibodies. However, SABA may produce false-positive results for anti-HLA antibodies. Herein, we analyzed the data of patients with complement-dependent cytotoxic crossmatch-/flow cytometric crossmatch-/SABA+/- results to determine false-positive results for anti-HLA antibodies. We also determined the prevalence of false-positive results by comparing false-positive data from our laboratory and national allele frequency data obtained with high-resolution HLA typing. For HLA-A, -B, -C, and -DR, a ratio of positive frequency to allele frequency of ≥3 in our laboratory was considered a false-positive result. For HLA-DQA1/DQB1 and HLA-DPA1/DPB1, we considered the positive frequency of ≥3 as a false positive result due to lack of haplotype frequency data. SABA results from 284 patients (78.0%) demonstrated false reactivity. The antibody against HLA-C*17:01 displayed the highest frequency ratio (298.3). If false-positive reactivity is suspected, results should be confirmed using different methods. If confirmation tests are unfeasible, comparing the allele frequency with the positive rate of detected anti-HLA antibodies and using a ratio ≥3 may facilitate the interpretation of SABA results. The positive rate of anti-HLA antibodies can be validated using the HLA allele frequency of the population to determine false-positive results.

Keywords: Allele frequency; Antibodies; Human leukocyte antigen; Single-antigen bead assay; Transplantation.

MeSH terms

  • Antibodies / metabolism*
  • Complement System Proteins / metabolism
  • False Positive Reactions
  • Gene Frequency
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Histocompatibility Testing
  • Humans
  • Immunomagnetic Separation / methods*
  • Organ Transplantation
  • Sensitivity and Specificity

Substances

  • Antibodies
  • HLA Antigens
  • Complement System Proteins