Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation
(2020) In Blood Advances 4(16). p.3875-3885- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020-08-25
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood Advances
- volume
- 4
- issue
- 16
- pages
- 11 pages
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:32810222
- scopus:85090322617
- ISSN
- 2473-9529
- DOI
- 10.1182/bloodadvances.2020002291
- language
- English
- LU publication?
- yes
- id
- 3a0643d4-5b43-4441-8429-029e5e3337b5
- date added to LUP
- 2020-10-19 11:37:55
- date last changed
- 2024-05-01 18:19:15
@article{3a0643d4-5b43-4441-8429-029e5e3337b5,
abstract = {{<p>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.</p>}},
author = {{Van Der Laan, Eveline A.N.Zeeuw and Van Der Velden, Saskia and Bentlage, Arthur E.H. and Larsen, Mads D. and Van Osch, Thijs L.J. and Mok, Juk Yee and Brasser, Giso and Geerdes, Dionne M. and Koeleman, Carolien A.M. and Nouta, Jan and Semple, John W. and Porcelijn, Leendert and Van Esch, Wim J.E. and Wuhrer, Manfred and Van Der Schoot, C. Ellen and Vidarsson, Gestur and Kapur, Rick}},
issn = {{2473-9529}},
language = {{eng}},
month = {{08}},
number = {{16}},
pages = {{3875--3885}},
publisher = {{American Society of Hematology}},
series = {{Blood Advances}},
title = {{Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation}},
url = {{http://dx.doi.org/10.1182/bloodadvances.2020002291}},
doi = {{10.1182/bloodadvances.2020002291}},
volume = {{4}},
year = {{2020}},
}