Anti-cysteine/spacer antibodies that open ADAMTS13 are a common feature in iTTP - Sorbonne Université Access content directly
Journal Articles Blood Advances Year : 2021

Anti-cysteine/spacer antibodies that open ADAMTS13 are a common feature in iTTP

Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by an autoantibody-mediated deficiency in ADAMTS13. In healthy individuals, ADAMTS13 has a folded conformation in which the central spacer (S) domain interacts with the C-terminal CUB domains. We recently showed that ADAMTS13 adopts an open conformation in iTTP and that patient immunoglobulin G antibodies (IgGs) can open ADAMTS13. Anti-ADAMTS13 autoantibodies in patients with iTTP are directed against the different ADAMTS13 domains, but almost all patients have autoantibodies binding to the cysteine/spacer (CS) domains. In this study, we investigated whether the autoantibodies against the CS and CUB domains can disrupt the S-CUB interaction of folded ADAMTS13, thereby opening ADAMTS13. To this end, we purified anti-CS and anti-CUB autoantibodies from 13 patients with acute iTTP by affinity chromatography. The successfully purified anti-CS (10/13 patients) and anti-CUB (4/13 patients) autoantibody fractions were tested further in our ADAMTS13 conformation enzyme-linked immunosorbent assay to study whether they could open ADAMTS13. Interestingly, all purified anti-CS fractions (10/10 patients) were able to open ADAMTS13. On the other hand, only half of the purified anti-CUB fractions (2/4 patients) opened ADAMTS13. Our finding highlights that anti-CS autoantibodies that open ADAMTS13 are a common feature of the autoimmune response in iTTP.
Fichier principal
Vignette du fichier
advancesadv2021004971.pdf (789.2 Ko) Télécharger le fichier
Origin Publisher files allowed on an open archive

Dates and versions

hal-03457592 , version 1 (30-11-2021)

Identifiers

Cite

Laure de Waele, Alexandre Curie, Kadri Kangro, Edwige Tellier, Gilles Kaplanski, et al.. Anti-cysteine/spacer antibodies that open ADAMTS13 are a common feature in iTTP. Blood Advances, 2021, 5 (21), pp.4480-4484. ⟨10.1182/bloodadvances.2021004971⟩. ⟨hal-03457592⟩
32 View
29 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More