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  • Van Der Laan, Eveline A.N.ZeeuwSanquin Research,Academic Medical Center of University of Amsterdam (AMC) (author)

Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-08-18
  • American Society of Hematology,2020
  • 11 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:3a0643d4-5b43-4441-8429-029e5e3337b5
  • https://lup.lub.lu.se/record/3a0643d4-5b43-4441-8429-029e5e3337b5URI
  • https://doi.org/10.1182/bloodadvances.2020002291DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusionrelated 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 TRALIcausing 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 FcgRs 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- A nd Fc-binding affinities for antigen and FcgRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction.

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  • Van Der Velden, SaskiaAcademic Medical Center of University of Amsterdam (AMC),Sanquin Research (author)
  • Bentlage, Arthur E.H.Sanquin Research,Academic Medical Center of University of Amsterdam (AMC) (author)
  • Larsen, Mads D.Academic Medical Center of University of Amsterdam (AMC),Sanquin Research (author)
  • Van Osch, Thijs L.J.Sanquin Research,Academic Medical Center of University of Amsterdam (AMC) (author)
  • Mok, Juk YeeSanquin Reagents (author)
  • Brasser, GisoSanquin Reagents (author)
  • Geerdes, Dionne M.Sanquin Reagents (author)
  • Koeleman, Carolien A.M.Leiden University Medical Centre (author)
  • Nouta, JanLeiden University Medical Centre (author)
  • Semple, John W.Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)jo0201se (author)
  • Porcelijn, LeendertSanquin Diagnostic Services (author)
  • Van Esch, Wim J.E.Sanquin Reagents (author)
  • Wuhrer, ManfredLeiden University Medical Centre (author)
  • Van Der Schoot, C. EllenSanquin Research,Academic Medical Center of University of Amsterdam (AMC) (author)
  • Vidarsson, GesturAcademic Medical Center of University of Amsterdam (AMC),Sanquin Research (author)
  • Kapur, RickAcademic Medical Center of University of Amsterdam (AMC),Sanquin Research(Swepub:lu)ri1121ka (author)
  • Sanquin ResearchAcademic Medical Center of University of Amsterdam (AMC) (creator_code:org_t)

Related titles

  • In:Blood Advances: American Society of Hematology4:16, s. 3875-38852473-95292473-9537

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