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

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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- (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- 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- 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.


  • Eveline A.N.Zeeuw Van Der Laan
  • Saskia Van Der Velden
  • Arthur E.H. Bentlage
  • Mads D. Larsen
  • Thijs L.J. Van Osch
  • Juk Yee Mok
  • Giso Brasser
  • Dionne M. Geerdes
  • Carolien A.M. Koeleman
  • Jan Nouta
  • John W. Semple
  • Leendert Porcelijn
  • Wim J.E. Van Esch
  • Manfred Wuhrer
  • C. Ellen Van Der Schoot
  • Gestur Vidarsson
  • Rick Kapur
External organisations
  • Academic Medical Center of University of Amsterdam (AMC)
  • Sanquin Reagents
  • Sanquin Diagnostic Services
  • Sanquin Research
  • Leiden University Medical Centre
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)3875-3885
Number of pages11
JournalBlood Advances
Issue number16
Publication statusPublished - 2020 Aug 25
Publication categoryResearch