{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T07:51:42Z","timestamp":1747381902075,"version":"3.37.3"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000014","name":"Canadian Blood Services","doi-asserted-by":"publisher","award":["Not apply"],"award-info":[{"award-number":["Not apply"]}],"id":[{"id":"10.13039\/501100000014","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Government | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Not apply"],"award-info":[{"award-number":["Not apply"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts primarily due to antiplatelet autoantibodies. Anti-D is a donor-derived polyclonal Ab against the rhesus D Ag on erythrocytes used to treat ITP. Unfortunately, adverse inflammatory\/hypersensitivity reactions and a Food and Drug Administration\u2013issued black box warning have limited its clinical use. This underscores the imperative to understand the inflammatory pathway associated with anti-erythrocyte Ab-based therapies. TER119 is an erythrocyte-specific Ab with anti-D-like therapeutic activity in murine ITP, while also exhibiting a distinct inflammatory signature involving production of CCL2, CCL5, and CXCL9 but not IFN-\u03b3. Therefore, TER119 has been used to elucidate the potential mechanism underlying the adverse inflammatory activity associated with anti-erythrocyte Ab therapy in murine ITP. Prior work has demonstrated that TER119 administration is associated with a dramatic decrease in body temperature and inflammatory cytokine\/chemokine production. The work presented in the current study demonstrates that inhibiting the highly inflammatory platelet-activating factor (PAF) pathway with PAF receptor antagonists prevents TER119-driven changes in body temperature and inhibits the production of the CCL2, CCL5, and CXCL9 inflammatory cytokines in CD-1 mice. Phagocytic cells and a functional TER119 Fc region were found to be necessary for TER119-induced body temperature changes and increases in CXCL9 and CCL2. Taken together, this work reveals the novel requirement of the PAF pathway in causing adverse inflammatory activity associated with anti-erythrocyte Ab therapy in a murine model and provides a strategy of mitigating these potential reactions without altering therapeutic activity.<\/jats:p>","DOI":"10.4049\/jimmunol.2300638","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T13:20:52Z","timestamp":1710940852000},"page":"1531-1539","source":"Crossref","is-referenced-by-count":1,"title":["Antagonism of the Platelet-Activating Factor Pathway Mitigates Inflammatory Adverse Events Driven by Anti-erythrocyte Antibody Therapy in Mice"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-3948","authenticated-orcid":false,"given":"Kevin Doyoon","family":"Won","sequence":"first","affiliation":[{"name":"Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Unity Health Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine and Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Temerty Faculty of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3042-8919","authenticated-orcid":false,"given":"Lazaro","family":"Gil Gonzalez","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Unity Health Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoelys","family":"Cruz-Leal","sequence":"additional","affiliation":[{"name":"Innovation and Portfolio Management, Canadian Blood Services , Ottawa, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9699-8933","authenticated-orcid":false,"given":"Alequis","family":"Pavon Oro","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Unity Health Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5051-6916","authenticated-orcid":false,"given":"Alan H","family":"Lazarus","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital, Unity Health Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Medicine and Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Temerty Faculty of Medicine, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Innovation and Portfolio Management, Canadian Blood Services , Ottawa, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2025020405493258000_r1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3390\/jcm6020016","article-title":"Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP)","volume":"6","author":"Zufferey","year":"2017","journal-title":"J. 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