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Identification of the factor XII contact activation site enables sensitive coagulation diagnostics

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Identification of the factor XII contact activation site enables sensitive coagulation diagnostics. / Heestermans, Marco; Naudin, Clément; Mailer, Reiner K; Konrath, Sandra; Klaetschke, Kristin; Jämsä, Anne; Frye, Maike; Deppermann, Carsten; Pula, Giordano; Kuta, Piotr; Friese, Manuel A; Gelderblom, Mathias; Sickmann, Albert; Preston, Roger J S; Nofer, Jerzy-Roch; Rose-John, Stefan; Butler, Lynn M; Salomon, Ophira; Stavrou, Evi X; Renné, Thomas.

in: NAT COMMUN, Jahrgang 12, Nr. 1, 22.09.2021, S. 5596 - 5613.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Heestermans, M, Naudin, C, Mailer, RK, Konrath, S, Klaetschke, K, Jämsä, A, Frye, M, Deppermann, C, Pula, G, Kuta, P, Friese, MA, Gelderblom, M, Sickmann, A, Preston, RJS, Nofer, J-R, Rose-John, S, Butler, LM, Salomon, O, Stavrou, EX & Renné, T 2021, 'Identification of the factor XII contact activation site enables sensitive coagulation diagnostics', NAT COMMUN, Jg. 12, Nr. 1, S. 5596 - 5613. https://doi.org/10.1038/s41467-021-25888-7

APA

Heestermans, M., Naudin, C., Mailer, R. K., Konrath, S., Klaetschke, K., Jämsä, A., Frye, M., Deppermann, C., Pula, G., Kuta, P., Friese, M. A., Gelderblom, M., Sickmann, A., Preston, R. J. S., Nofer, J-R., Rose-John, S., Butler, L. M., Salomon, O., Stavrou, E. X., & Renné, T. (2021). Identification of the factor XII contact activation site enables sensitive coagulation diagnostics. NAT COMMUN, 12(1), 5596 - 5613. https://doi.org/10.1038/s41467-021-25888-7

Vancouver

Heestermans M, Naudin C, Mailer RK, Konrath S, Klaetschke K, Jämsä A et al. Identification of the factor XII contact activation site enables sensitive coagulation diagnostics. NAT COMMUN. 2021 Sep 22;12(1):5596 - 5613. https://doi.org/10.1038/s41467-021-25888-7

Bibtex

@article{7924f63fdfa948e195b89d2c1e38a6f8,
title = "Identification of the factor XII contact activation site enables sensitive coagulation diagnostics",
abstract = "Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317-Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317-Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317-Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.",
author = "Marco Heestermans and Cl{\'e}ment Naudin and Mailer, {Reiner K} and Sandra Konrath and Kristin Klaetschke and Anne J{\"a}ms{\"a} and Maike Frye and Carsten Deppermann and Giordano Pula and Piotr Kuta and Friese, {Manuel A} and Mathias Gelderblom and Albert Sickmann and Preston, {Roger J S} and Jerzy-Roch Nofer and Stefan Rose-John and Butler, {Lynn M} and Ophira Salomon and Stavrou, {Evi X} and Thomas Renn{\'e}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = sep,
day = "22",
doi = "10.1038/s41467-021-25888-7",
language = "English",
volume = "12",
pages = "5596 -- 5613",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Identification of the factor XII contact activation site enables sensitive coagulation diagnostics

AU - Heestermans, Marco

AU - Naudin, Clément

AU - Mailer, Reiner K

AU - Konrath, Sandra

AU - Klaetschke, Kristin

AU - Jämsä, Anne

AU - Frye, Maike

AU - Deppermann, Carsten

AU - Pula, Giordano

AU - Kuta, Piotr

AU - Friese, Manuel A

AU - Gelderblom, Mathias

AU - Sickmann, Albert

AU - Preston, Roger J S

AU - Nofer, Jerzy-Roch

AU - Rose-John, Stefan

AU - Butler, Lynn M

AU - Salomon, Ophira

AU - Stavrou, Evi X

AU - Renné, Thomas

N1 - © 2021. The Author(s).

PY - 2021/9/22

Y1 - 2021/9/22

N2 - Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317-Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317-Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317-Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.

AB - Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317-Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317-Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317-Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.

U2 - 10.1038/s41467-021-25888-7

DO - 10.1038/s41467-021-25888-7

M3 - SCORING: Journal article

C2 - 34552086

VL - 12

SP - 5596

EP - 5613

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -