دورية أكاديمية
Trogocytosis drives red blood cell antigen loss in association with antibody-mediated immune suppression.
| العنوان: | Trogocytosis drives red blood cell antigen loss in association with antibody-mediated immune suppression. |
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| المؤلفون: | Cruz-Leal Y; Innovation and Portfolio Management, Canadian Blood Services, Ottawa, ON, Canada.; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Norris PAA; Innovation and Portfolio Management, Canadian Blood Services, Ottawa, ON, Canada.; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden., Gil Gonzalez L; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Marjoram D; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Wabnitz H; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Shan Y; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Lazarus AH; Innovation and Portfolio Management, Canadian Blood Services, Ottawa, ON, Canada.; Keenan Research Centre for Biomedical Science, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Department of Medicine, University of Toronto, Toronto, ON, Canada. |
| المصدر: | Blood [Blood] 2024 Feb 29; Vol. 143 (9), pp. 807-821. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Trogocytosis* , Erythroblastosis, Fetal*, Pregnancy ; Infant, Newborn ; Female ; Mice ; Humans ; Animals ; Antibodies ; Erythrocytes/metabolism ; Immunosuppression Therapy ; Isoantibodies |
| مستخلص: | Abstract: Red blood cell (RBC) alloimmunization to paternal antigens during pregnancy can cause hemolytic disease of the fetus and newborn (HDFN). This severe and potentially fatal neonatal disorder can be prevented by the administration of polyclonal anti-D through a mechanism referred to as antibody-mediated immune suppression (AMIS). Although anti-D prophylaxis effectively prevents HDFN, a lack of mechanistic clarity has hampered its replacement with recombinant agents. The major theories behind AMIS induction in the hematologic literature have classically centered around RBC clearance; however, antigen modulation/loss has recently been proposed as a potential mechanism of AMIS. To explore the primary mechanisms of AMIS, we studied the ability of 11 different antibodies to induce AMIS, RBC clearance, antigen loss, and RBC membrane loss in the HOD (hen egg lysozyme-ovalbumin-human Duffy) murine model. Antibodies targeting different portions of the HOD molecule could induce AMIS independent of their ability to clear RBCs; however, all antibodies capable of inducing a strong AMIS effect also caused significant in vivo loss of the HOD antigen in conjunction with RBC membrane loss. In vitro studies of AMIS-inducing antibodies demonstrated simultaneous RBC antigen and membrane loss, which was mediated by macrophages. Confocal live-cell microscopy revealed that AMIS-inducing antibodies triggered RBC membrane transfer to macrophages, consistent with trogocytosis. Furthermore, anti-D itself can induce trogocytosis even at low concentrations, when phagocytosis is minimal or absent. In view of these findings, we propose trogocytosis as a mechanism of AMIS induction. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.) |
| التعليقات: | Comment in: Blood. 2024 Feb 29;143(9):742-744. (PMID: 38421815) |
| المشرفين على المادة: | 0 (Antibodies) 0 (Isoantibodies) |
| تواريخ الأحداث: | Date Created: 20231110 Date Completed: 20240301 Latest Revision: 20240324 |
| رمز التحديث: | 20240324 |
| DOI: | 10.1182/blood.2023020860 |
| PMID: | 37946269 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood.2023020860 |