Rituximab leads to early elimination of circulating CD20(+) T and B lymphocytes in patients with iTTP despite ongoing TPEx

• Type of Material: Article
• Authors: Marcus A. Carden, University of North Carolina; Manila Gaddh, Emory University; Abhinav Hoskote, Mount Sinai Saint Luke's Hospital; Michael Brown, Emory University; Virginia Merrill, Emory University; Sean Stowell, Emory University; Shanmuganathan Chandrakasan, Emory University; Ana Antun, Emory University; Ragini Kudchadkar, Emory University; Sarah Kotanchiyev, Emory University; David Jaye, Emory University; Imre Bodo, Emory University
• Language: English
• Date: 2020-02-11
• Publisher: ASH Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by The American Society of Hematology
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2019001148
• Title of Journal or Parent Work: Blood Advances
• Volume: 4
• Issue: 3
• Start Page: 477
• End Page: 481
• Grant/Funding Information: This work was supported by the National Institutes of Health through National Center for Advancing Translational Sciences grant KL2TR002490 (M.A.C.) and the Hungarian National Research Development and Innovation Office (NFKI) grant OTKA-K19_131945 (I.B.).
• Keywords: CD20 antigens; Life Sciences & Biomedicine; Depletion; Rituximab; Hematology; Cells; Plasma exchange; Science & Technology; B-lymphocytes
• Research Categories: Biology, Cell; Health Sciences, Pathology; Health Sciences, Pharmacy; Health Sciences, Oncology

Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy associated with severe deficiency in ADAMTS13, a disintegrin and metalloprotease responsible for limiting abnormally high concentrations of ultra-large von Willebrand factor multimers in the plasma of humans.1,2 Classically, iTTP results from B-cell production of immunoglobulin G (IgG) autoantibodies to ADAMTS13, leading to critically low activity levels (<10%) and formation of platelet-rich thrombi with thrombocytopenia, hemolytic anemia, and schistocytes under high-shear conditions in the microvasculature.3 Management of iTTP involves safely and quickly initiating immunomodulating agents targeting rogue lymphocytes responsible for IgG production alongside a treatment backbone of therapeutic plasma exchange (TPEx), which repletes ADAMTS13 and removes autoantibodies.4