Autoantibodies to ADAMTS13 in human immunodeficiency virus-associated thrombotic thrombocytopenic purpura.

Autor: Meiring M; Department of Haematology and Cell Biology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.; Universitas Business Unit, National Health Laboratory Service, Bloemfontein, South Africa., Khemisi M; Department of Haematology and Cell Biology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.; Universitas Business Unit, National Health Laboratory Service, Bloemfontein, South Africa., Louw S; Universitas Business Unit, National Health Laboratory Service, Bloemfontein, South Africa.; Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa., Krishnan P; Department of Haematology and Cell Biology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
Jazyk: angličtina
Zdroj: Vox sanguinis [Vox Sang] 2024 Sep 18. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1111/vox.13738
Abstrakt: Background and Objectives: Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal thrombotic microangiopathic disorder that can result from human immunodeficiency virus (HIV) infection. The pathogenesis involves a deficiency of the von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs member 13) and the presence of anti-ADAMTS13 autoantibodies. However, there is insufficient information regarding the epitope specificity and reactivity of these autoantibodies. This study aimed to perform epitope-mapping analysis to provide novel insights into the specific epitopes on ADAMTS13 domains affected by autoantibodies.
Materials and Methods: The study analysed 59 frozen citrate plasma samples from HIV-associated TTP patients in South Africa, measuring ADAMTS13 activity using Technozyme® ADAMTS13 activity test, total immunoglobulin (Ig) M and IgA antibodies levels using ELISA kit and purifying IgG antibodies using NAb™ Protein G spin columns. A synthetic ADAMTS13 peptide library was used for epitope mapping.
Results: Overall, 90% of samples showed anti-ADAMTS13 IgG autoantibodies, with 64% of these antibodies being inhibitory, as revealed by mixing studies. Samples with ADAMTS13 antigen levels below 5% showed high anti-ADAMTS13 IgG autoantibody titres (≥50 IU/mL), whereas those with 5%-10% levels had low autoantibody titres (<50 IU/mL).The metalloprotease, cysteine-rich and spacer domains were 100% involved in binding anti-ADAMTS13 IgG antibodies, with 58% of samples containing antibodies binding to the C-terminal part of the ADAMTS13 disintegrin-like domain, indicating different pathogenic mechanisms.
Conclusion: The metalloprotease, cysteine-rich and spacer domains are the primary targets for anti-ADAMTS13 IgG autoantibodies in patients with HIV-associated TTP. These findings suggest potential effects on the proteolytic activity of ADAMTS13, highlighting the complex nature of the pathogenic mechanisms involved.
(© 2024 The Author(s). Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)
Databáze: MEDLINE
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