biostudies-literatureUnknown9(20)Postmus T<h4>Abstract</h4>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening thrombotic disorder, which results from the development of autoantibodies targeting ADAMTS13. Most patients (>90%) with iTTP display antibodies against a shared epitope in the spacer domain of ADAMTS13. Nevertheless, a smaller population of patients (20%-40%) also has antibodies directed toward the CUB (complement C1r/C1s, Uegf, Bmp1) domains of ADAMTS13. Here, we explored whether anti-CUB antibodies have a shared epitope located on CUB domains of ADAMTS13 that overlaps with the spacer-CUB domain interface. Hydrogen-deuterium exchange mass spectrometry revealed that a panel of patient-derived human monoclonal anti-CUB domain antibodies specifically targeted peptides 1248-1253 and 1359-137Blood advances5350-5361https://www.ebi.ac.uk/biostudies/studies/S-EPMC12597635biostudies-literatureTrp1250, Lys1252, and Arg1367 of ADAMTS13 comprise a hot spot for anti-CUB domain antibodies in patients with iTTP.PMC12597635Hoogendijk AJvan Alphen FPostmus TKaijen PVeyradier ACoppo Pvan der Zwaan CVanhoorelbeke KNicolaes GJansen RVoorberg JJoly BSfalseTrp1250, Lys1252, and Arg1367 of ADAMTS13 comprise a hot spot for anti-CUB domain antibodies in patients with iTTP.<h4>Abstract</h4>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening thrombotic disorder, which results from the development of autoantibodies targeting ADAMTS13. Most patients (>90%) with iTTP display antibodies against a shared epitope in the spacer domain of ADAMTS13. Nevertheless, a smaller population of patients (20%-40%) also has antibodies directed toward the CUB (complement C1r/C1s, Uegf, Bmp1) domains of ADAMTS13. Here, we explored whether anti-CUB antibodies have a shared epitope located on CUB domains of ADAMTS13 that overlaps with the spacer-CUB domain interface. Hydrogen-deuterium exchange mass spectrometry revealed that a panel of patient-derived human monoclonal anti-CUB domain antibodies specifically targeted peptides 1248-1253 and 1359-1372025-01-01T00:00:00Z2025 Oct2026-06-05T12:23:15.263Z2026-05-16T03:12:34.133ZS-EPMC125976354077956910.1182/bloodadvances.2025017193