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Alloantibodies recognizing these blood group antigens determine blood compatibility, and the transfusion of incompatible blood can lead to life\u2010threatening 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\u2010CD38 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)\u2010fusion constructs, referred to as \u201cbaitbodies\u201d, designed to neutralize anti\u2010CD38 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\u2010phase red cell adherence assays. The CD38\u2010mFc baitbody successfully prevented agglutination reactions induced by three clinically relevant anti\u2010CD38 monoclonal antibodies\u2014daratumumab, felzartamab and isatuximab\u2014in spiked samples. This allowed the detection of alloantibodies of the Rhesus, Kell and Duffy blood groups without interference. The CD38\u2010mFc construct also demonstrated potential in a head\u2010to\u2010head comparison with commercial mitigation reagents, DaraEx and Grifols sCD38. Finally, the CD38\u2010mFc baitbody effectively neutralized daratumumab in patient samples, preventing false positive test outcomes.<\/jats:p>","DOI":"10.1155\/jimr\/7343647","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:17:47Z","timestamp":1767593867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Resolving the Interference of Anti\u2010CD38 Antibodies on Blood Compatibility Assays Using CD38 \u201cBaitbodies\u201d Approach"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7537-023X","authenticated-orcid":false,"given":"Dianne Celine","family":"Gnann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-954X","authenticated-orcid":false,"given":"Stephan","family":"Steinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrikus S. 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