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Updated: Apr 16, 2026

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
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Resolving the daratumumab interference with blood compatibility testing.

Claudia I Chapuy1, Rachel T Nicholson1, Maria D Aguad1

  • 1Blood Bank, Department of Pathology, Brigham and Women's Hospital.

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|March 13, 2015
PubMed
Summary
This summary is machine-generated.

Daratumumab causes false positive blood test results by binding to CD38 on red blood cells. Dithiothreitol treatment of red blood cells prevents this interference, ensuring safe blood transfusions for patients.

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Area of Science:

  • Hematology
  • Immunology
  • Transfusion Medicine

Background:

  • Daratumumab (DARA) is an IgG1κ monoclonal antibody targeting CD38 for multiple myeloma treatment.
  • DARA-treated patients' plasma showed positive antibody screens and panreactivity in red blood cell (RBC) compatibility testing.
  • This interference was hypothesized to be DARA binding to CD38 on reagent RBCs.

Purpose of the Study:

  • To investigate the cause of DARA-induced panreactivity in blood compatibility testing.
  • To identify methods to prevent DARA interference with serologic testing.

Main Methods:

  • Assessed DARA binding to CD38+ and CD38- HL60 cells via flow cytometry.
  • Utilized dithiothreitol (DTT) or trypsin to remove cell surface CD38.
  • Neutralized DARA using soluble CD38 or anti-DARA.
  • Tested patient samples and spiked normal plasma using routine blood bank methods.

Main Results:

  • DARA spiked into normal plasma mimicked the interference seen in DARA-treated patients.
  • Flow cytometry confirmed DARA binds to CD38+ cells but not CD38- cells.
  • DTT treatment reduced DARA binding by 92% by denaturing CD38.
  • Soluble CD38 or anti-DARA also inhibited DARA binding.

Conclusions:

  • Daratumumab causes in vitro panreactivity by binding to CD38 on reagent RBCs.
  • Treating reagent RBCs with DTT effectively negates DARA interference.
  • DTT treatment allows for safe blood provision to DARA-treated patients, with K- units supplied due to DTT's effect on Kell antigens.