Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation
| Autor: | Giso Brasser, Arthur E. H. Bentlage, Saskia van der Velden, Manfred Wuhrer, Wim J E van Esch, Leendert Porcelijn, Juk Yee Mok, Gestur Vidarsson, John W. Semple, Dionne M Geerdes, Rick Kapur, Thijs L. J. van Osch, Mads Delbo Larsen, Carolien A. M. Koeleman, Eveline A.N. Zeeuw van der Laan, Jan Nouta, C. Ellen van der Schoot |
|---|---|
| Přispěvatelé: | ACS - Atherosclerosis & ischemic syndromes, Landsteiner Laboratory, Graduate School, AII - Inflammatory diseases |
| Rok vydání: | 2020 |
| Předmět: |
Glycan
Mice Inbred BALB C Glycosylation biology Chemistry Transfusion Medicine Transfusion Reaction Hematology Lung injury Major histocompatibility complex Complement system Mice Inbred C57BL chemistry.chemical_compound Mice Transfusion-Related Acute Lung Injury Antigen Immunology MHC class I biology.protein Animals Antibody Complement Activation |
| Zdroj: | Blood Adv Blood advances, 4(16), 3875-3885. American Society of Hematology Blood Advances, 4(16), 3875-3885. AMER SOC HEMATOLOGY |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all anti-leukocyte antibodies cause TRALI. It has been shown that the anti–major histocompatibility complex (MHC) class I antibody 34-1-2S (anti–H-2Kd) causes TRALI in BALB/c mice (MHC class I haplotype H-2Kd), whereas SF1.1.10 (anti–H-2Kd) does not. In C57BL/6 mice (MHC class I haplotype H-2Kb), TRALI only occurs when anti-MHC class I antibody AF6-88.5.5.3 (anti–H-2Kb) is administered together with a high dose of 34-1-2S. It remains unknown which specific antibody characteristics are responsible for eliciting TRALI. We therefore investigated several biological and structural features of 34-1-2S compared with other anti-MHC class I antibodies, which on their own do not cause TRALI: SF1.1.10 and AF6-88.5.5.3. No substantial differences were observed between the TRALI-causing 34-1-2S and the TRALI-resistant SF1.1.10 regarding binding affinity to H-2Kd. Regarding binding affinity to H-2Kb, only AF6-88.5.5.3 potently bound to H-2Kb, whereas 34-1-2S exhibited weak but significant cross-reactivity. Furthermore, the binding affinity to FcγRs as well as the Fc glycan composition seemed to be similar for all antibodies. Similar Fc glycosylation profiles were also observed for human TRALI-causing donor anti-HLA antibodies compared with human anti-HLA antibodies from control donors. 34-1-2S, however, displayed superior complement activation capacity, which was fully Fc dependent and not significantly dependent on Fc glycosylation. We conclude that TRALI induction is not correlated with Fab- and Fc-binding affinities for antigen and FcγRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|