Trp1250, Lys1252, and Arg1367 of ADAMTS13 comprise a hot spot for anti-CUB domain antibodies in patients with iTTP.

ABSTRACT:

Abstract

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 1359-137

SUBMITTER: Postmus T 

PROVIDER: S-EPMC12597635 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature