Can solid phase assays be better utilized to measure efficacy of antibody removal therapies?

Anat R. Tambur*, Denis Glotz, Nancy D. Herrera, Erik N. Chatroop, Tal Roitberg, John J. Friedewald, David Gjertson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment. MFI values of IgG and C1q single-antigen-bead assays were compared with antibody titer values (serial dilutions). Antibody reduction was tracked and the differences in pre-to-post-treatment values were calculated as delta-reduction of antibody levels. Dynamic patterns of titration studies reduced effects of serum-inherent inhibitory factors (prozone-like); eliminated over-saturation limitations, and provided better estimation of antibody-binding strength compared with the other methods. Moreover, delta-reduction of antibody values using titration studies was significantly more uniform compared with either IgG or C1q tests. Analyzing antibody results using only C1q positive or only higher MFI values did not change the overall magnitude of results. Overall, titration studies provided better estimate of responsiveness to treatment and thus can serve as companion to monitoring efficacy of antibody-removal therapies.

Original languageEnglish (US)
Pages (from-to)624-630
Number of pages7
JournalHuman Immunology
Volume77
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • AMR
  • Desensitization
  • HLA antibody
  • Luminex
  • MFI
  • SAB
  • Titer

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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