{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:15:41Z","timestamp":1792790141527,"version":"4.5.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Answering T.T.P. foundation","award":["project number 1009"],"award-info":[{"award-number":["project number 1009"]}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030-160269"],"award-info":[{"award-number":["310030-160269"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011012","name":"Gesellschaft f\u00fcr Thrombose- und H\u00e4mostaseforschung","doi-asserted-by":"publisher","award":["GTH congress presidential fund of 2017"],"award-info":[{"award-number":["GTH congress presidential fund of 2017"]}],"id":[{"id":"10.13039\/501100011012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rare immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease resulting from a severe autoantibody-mediated ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13) deficiency. Acute iTTP episodes are medical emergencies, but when treated appropriately &amp;gt;95% of patients survive. However, at least half of survivors will eventually experience a relapse. How remission of an initial episode is achieved and factors contributing to reemergence of anti-ADAMTS13 Abs and a relapsing course are poorly understood. In acquired hemophilia and systemic lupus erythematosus, anti-idiotypic Abs counteracting and neutralizing pathogenic autoantibodies contribute to remission. We selected and amplified the splenic anti-idiotypic IgG1 Fab \u03ba\/\u03bb repertoire of two relapsing iTTP patients on previously generated monoclonal inhibitory anti-ADAMTS13 Fabs by phage display to explore whether anti-idiotypic Abs have a role in iTTP. We obtained 27 single anti-idiotypic Fab clones, half of which had unique sequences, although both patients shared four H chain V region genes (VH1-69*01, VH3-15*01, VH3-23*01, and VH3-49*03). Anti-idiotypic Fab pools of both patients fully neutralized the inhibitor capacity of the monoclonal anti-ADAMTS13 Abs used for their selection. Preincubation of plasma samples of 22 unrelated iTTP patients stratified according to functional ADAMTS13 inhibitor titers (&amp;gt;2 Bethesda units\/ml, or 1\u20132 Bethesda units\/ml), with anti-idiotypic Fab pools neutralized functional ADAMTS13 inhibitors and restored ADAMTS13 activity in 18\u201345% of those cases. Taken together, we present evidence for the presence of an anti-idiotypic immune response in iTTP patients. The interindividual generalizability of this response is limited despite relatively uniform pathogenic anti-ADAMTS13 Abs recognizing a dominant epitope in the ADAMTS13 spacer domain.<\/jats:p>","DOI":"10.4049\/jimmunol.2100868","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T15:20:52Z","timestamp":1657725652000},"page":"2497-2507","source":"Crossref","is-referenced-by-count":3,"title":["Naturally Occurring Anti-Idiotypic Antibodies Portray a Largely Private Repertoire in Immune-Mediated Thrombotic Thrombocytopenic Purpura"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-8700","authenticated-orcid":false,"given":"Silvan R","family":"Heeb","sequence":"first","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern , Bern, ; and , Bern,","place":["Switzerland Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern, ; and , Bern,","place":["Switzerland Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5002-2238","authenticated-orcid":false,"given":"Monica","family":"Schaller","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern , Bern, ; and , Bern,","place":["Switzerland Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern, ; and , Bern,","place":["Switzerland Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1300-7135","authenticated-orcid":false,"given":"Johanna A","family":"Kremer Hovinga","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern , Bern, ; and , Bern,","place":["Switzerland Switzerland"]},{"name":"Department for BioMedical Research, University of Bern , Bern, ; and , Bern,","place":["Switzerland Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"2025021009065482700_r1","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1182\/blood.V89.9.3097","article-title":"Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura","volume":"89","author":"Furlan","year":"1997","journal-title":"Blood"},{"key":"2025021009065482700_r2","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1056\/NEJM199811263392202","article-title":"von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome","volume":"339","author":"Furlan","year":"1998","journal-title":"N. 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Haemost."},{"key":"2025021009065482700_r6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1182\/blood.2019000954","article-title":"How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns","volume":"134","author":"Mazepa","year":"2019","journal-title":"Blood"},{"key":"2025021009065482700_r7","doi-asserted-by":"crossref","first-page":"17020","DOI":"10.1038\/nrdp.2017.20","article-title":"Thrombotic thrombocytopenic purpura","volume":"3","author":"Kremer Hovinga","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2025021009065482700_r8","doi-asserted-by":"crossref","first-page":"1076029618825309","DOI":"10.1177\/1076029618825309","article-title":"Comparison of the long-term remission of rituximab and conventional treatment for acquired thrombotic thrombocytopenic purpura: a systematic review and meta-analysis","volume":"25","author":"Owattanapanich","year":"2019","journal-title":"Clin. Appl. Thromb. 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