Resolving the Interference of Anti-CD38 Antibodies on Blood Compatibility Assays Using CD38 “Baitbodies” Approach

Sep 29, 2026

Uploaded by Pentious

Blood transfusion safety relies on rapid, accurate blood compatibility testing. Alloantibodies against blood group antigens determine compatibility, while transfusion of incompatible blood can trigger life-threatening hemolytic reactions. Therapeutic anti-CD38 antibodies used in cancer immunotherapy interfere with testing because CD38 is expressed on red blood cells, creating false positives that can hide clinically relevant alloantibodies and delay safe supply. This work develops Fc-fusion “baitbodies” to neutralize anti-CD38 antibodies and prevent assay interference.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Therapeutic anti-CD38 antibodies and transfusion testing interference

Baitbody mitigation strategy using CD38-Fc fusion proteins

Assay evaluation and neutralization in relevant samples

Wiley Journal of Immunology Research Volume 2026, Article ID 7343647, 13 pages [https://doi.org/10.1155/jimr/7343647](https://doi.org/10.1155/jimr/7343647) Research Article Resolving the Interference of Anti-CD38 Antibodies on Blood Compatibility Assays Using CD38 “Baitbodies” Approach Dianne Celine Gnann , 1 Stephan Steinke , 1 Hendrikus S. P. Garritsen,2,3 and Michael Hust 1 1Abteilung Medizinische Biotechnologie, Institut für Biochemie, Biotechnologie und Bioinformatik, Technische Universität Braunschweig, Braunschweig 38106, Germany 2Institute for Clinical Transfusion Medicine, Celler Städtische Klinikum Braunschweig gGmbH, Braunschweig 38114, Germany 3Fraunhofer Institute for Surface Engineering and Thin Films IST, Braunschweig 38108, Germany Correspondence should be addressed to Michael Hust; [m.hust@tu-bs.de](m.hust@tu-bs.de) Received 5 August 2025; Revised 13 October 2025; Accepted 11 November 2025 Academic Editor: Poorani Gurumallesh Prabu Copyright © 2026 Dianne Celine Gnann et al. Journal of Immunology Research published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Blood transfusion safety depends on swift blood compatibility testing. Alloantibodies recognizing these blood group antigens determine blood compatibility, and the transfusion of incompatible blood can lead to life-threatening hemolytic transfusion reactions. Recently, the landscape of blood compatibility testing has been complicated due to the interference caused by therapeutic antibodies targeting CD38, a key target in cancer immunotherapy that is also expressed on red blood cells. The presence of anti-CD38 antibodies in blood samples has been found to bind to test or donor red blood cells, resulting in false positive tests. This interference poses a serious risk as it can potentially mask immunogenic alloantibodies and cause delays in supplying safe blood products. We present the development and application of fragment crystallizable (Fc)-fusion constructs, referred to as “baitbodies”, designed to neutralize anti-CD38 antibodies and mitigate false positive test outcomes. The extracellular domain of CD38 was fused to the Fc domain of a murine immunoglobulin G. These baitbody constructs were thoroughly characterized and applied in both serological microcolumn agglutination and automated solid-phase red cell adherence assays. The CD38-mFc baitbody successfully prevented agglutination reactions induced by three clinically relevant anti-CD38 monoclonal antibodies—daratumumab, felzartamab and isatuximab—in spiked samples. This allowed the detection of alloantibodies of the Rhesus, Kell and Duffy blood groups without interference. The CD38-mFc construct also demonstrated potential in a head-to-head comparison with commercial mitigation reagents, DaraEx and Grifols sCD38. Finally, the CD38-mFc baitbody effectively neutralized daratumumab in patient samples, preventing false positive test outcomes. 1. Introduction More than 200 therapeutic antibodies have received approval (EU EMA, US FDA, and other countries) for the treatment of hematologic and solid cancers, and many others are in phase III clinical studies (source: [antibodysociety.org](antibodysociety.org)). These antibodies are directed against cell surface protein markers on cancer cells. One such monoclonal therapeutic antibody is daratumumab. In preclinical investigations, daratumumab exhibited signiﬁcant cytotoxicity towards neoplastic cells through diverse pathways, such as complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, inducting apoptosis in these cells [1]. Besides the therapeutic effects of daratumumab, it can interfere with the immunophenotyping of tumor cells [2] . However, a far more relevant problem is caused with the provision of compatible blood prod

FAQs

Why do anti-CD38 therapeutic antibodies cause false positive blood compatibility results?

CD38 is present on red blood cells, so anti-CD38 antibodies bind to test or donor cells and induce (pan)agglutination. This masks detection of clinically relevant alloantibodies in the indirect anti-globulin test.

What is the “baitbodies” approach described in the study?

The study designs Fc-fusion constructs that neutralize anti-CD38 antibodies. The extracellular domain of CD38 is fused to the Fc domain of a murine IgG, aiming to prevent assay interference.

How was interference mitigated and validated experimentally?

The CD38-mFc baitbody was characterized and applied in serological microcolumn agglutination and automated solid-phase red cell adherence assays. It prevented agglutination induced by clinically relevant anti-CD38 monoclonal antibodies and enabled detection of Rhesus, Kell, and Duffy alloantibodies.

Sep 29, 2026

Uploaded by Pentious