{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T02:19:27Z","timestamp":1772504367055,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["SRUG210217586912"],"award-info":[{"award-number":["SRUG210217586912"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vox Sanguinis"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>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\u2010ADAMTS13 autoantibodies. However, there is insufficient information regarding the epitope specificity and reactivity of these autoantibodies. This study aimed to perform epitope\u2010mapping analysis to provide novel insights into the specific epitopes on ADAMTS13 domains affected by autoantibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The study analysed 59 frozen citrate plasma samples from HIV\u2010associated TTP patients in South Africa, measuring ADAMTS13 activity using Technozyme\u00ae ADAMTS13 activity test, total immunoglobulin (Ig) M and IgA antibodies levels using ELISA kit and purifying IgG antibodies using NAb\u2122 Protein G spin columns. A synthetic ADAMTS13 peptide library was used for epitope mapping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 90% of samples showed anti\u2010ADAMTS13 IgG autoantibodies, with 64% of these antibodies being inhibitory, as revealed by mixing studies. Samples with ADAMTS13 antigen levels below 5% showed high anti\u2010ADAMTS13 IgG autoantibody titres (\u226550\u2009IU\/mL), whereas those with 5%\u201310% levels had low autoantibody titres (&lt;50\u2009IU\/mL).The metalloprotease, cysteine\u2010rich and spacer domains were 100% involved in binding anti\u2010ADAMTS13 IgG antibodies, with 58% of samples containing antibodies binding to the C\u2010terminal part of the ADAMTS13 disintegrin\u2010like domain, indicating different pathogenic mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The metalloprotease, cysteine\u2010rich and spacer domains are the primary targets for anti\u2010ADAMTS13 IgG autoantibodies in patients with HIV\u2010associated TTP. These findings suggest potential effects on the proteolytic activity of ADAMTS13, highlighting the complex nature of the pathogenic mechanisms involved.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vox.13738","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:53:47Z","timestamp":1726707227000},"page":"1285-1294","source":"Crossref","is-referenced-by-count":1,"title":["Autoantibodies to ADAMTS13 in human immunodeficiency virus\u2010associated thrombotic thrombocytopenic purpura"],"prefix":"10.1111","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-7702","authenticated-orcid":false,"given":"Muriel","family":"Meiring","sequence":"first","affiliation":[{"name":"Department of Haematology and Cell Biology, Faculty of Health Sciences University of the Free State  Bloemfontein South\u00a0Africa"},{"name":"Universitas Business Unit National Health Laboratory Service  Bloemfontein South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mmakgabu","family":"Khemisi","sequence":"additional","affiliation":[{"name":"Department of Haematology and Cell Biology, Faculty of Health Sciences University of the Free State  Bloemfontein South\u00a0Africa"},{"name":"Universitas Business Unit National Health Laboratory Service  Bloemfontein South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4315-1496","authenticated-orcid":false,"given":"Susan","family":"Louw","sequence":"additional","affiliation":[{"name":"Universitas Business Unit National Health Laboratory Service  Bloemfontein South Africa"},{"name":"Department of Molecular Medicine and Haematology University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Palanisamy","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Haematology and Cell Biology, Faculty of Health Sciences University of the Free State  Bloemfontein South\u00a0Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020528"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100515200"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24612"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07276.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11739"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.06.007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4165"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH06-03-0135"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jca.21673"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2007.01346.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V118.21.4677.4677"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108083250604"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08636.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/597471"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/422363"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12959-018-0189-x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05325.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199715000-00009"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/341661"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-884700"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1672187"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH06-02-0100"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.4.954.bloodjournal794954"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.05.010"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(88)90012-5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(91)90043-A"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03568.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309872200"},{"key":"e_1_2_9_30_1","first-page":"307","article-title":"vWF proteolysis by adamts13 is dependent on cooperation between the ADAMTS13 cysteine\u2010rich domain loop Q456\u2010Q478 and the spacer domain","volume":"9","author":"Groot R","year":"2011","journal-title":"J Thromb Haemost"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.019299"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0908"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-235101"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502529200"}],"container-title":["Vox 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