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Thromb Haemost 2023; 123(09): 841-854
DOI: 10.1055/a-2057-8710
Coagulation and Fibrinolysis

Antibodies against Noncatalytic B Subunit of Factor XIII Inhibit Activation of Factor XIII and Fibrin Crosslinking

Masayoshi Souri
1   Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
3   Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Yonezawa, Japan
,
Chikako Yokoyama
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
4   Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yamagata, Japan
,
Tsukasa Osaki
1   Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
3   Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Yonezawa, Japan
,
Akitada Ichinose 
1   Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
› Institutsangaben Funding This study was supported in part by research aids to A.I. from the Japanese Ministry of Health, Labor, and Welfare (21FC1008), the Japanese Ministry of Education, Culture, Sports, Science, and Technology (16K09820), and the Japan Agency for Medical Research and Development (AMED; JP16ek0109043).
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Abstract

Background Coagulation factor XIII (FXIII) is a proenzyme of plasma transglutaminase. It comprises two catalytic A subunits (FXIII-A) and two carrier B subunits (FXIII-B). We previously reported that alloantibodies against FXIII-B could promote FXIII clearance in a patient with congenital FXIII-B deficiency who had received infusions of plasma-derived human FXIII (A2B2 heterotetramer).

Objectives We aimed to investigate whether anti-FXIII-B antibodies affect the catalytic function of FXIII.

Methods FXIII activation and fibrin crosslinking were examined in the presence of patient plasma, isolated patient IgG, or rat anti-FXIII-B monoclonal antibodies.

Results Alloantibody levels were increased by repeated infusions of plasma-derived A2B2 heterotetramer, which enhanced binding to the functionally important FXIII-B sushi domains. The patient plasma strongly inhibited cleavage of the FXIII-A activation peptide, amine incorporation, and fibrin crosslinking in normal plasma. Furthermore, anti-FXIII-B alloantibodies blocked the formation of the complex of FXIII-B with FXIII-A, and fibrinogen. Rat monoclonal antibodies against the 10th sushi domain of FXIII-B inhibited the incorporation of FXIII-B to fibrin, FXIII activation (i.e., cleavage of FXIII-A activation peptide), and ultimately fibrin crosslinking in normal plasma, independent of their effect on heterotetramer assembly with FXIII-A. Alloantibody binding to the A2B2 heterotetramer blocked the access of thrombin to the FXIII-A cleavage site, as indicated by the reaction of the alloantibodies to the A2B2 heterotetramer and FXIII-B, but not to FXIII-A.

Conclusion Anti-FXIII-B antibodies binding to the A2B2 heterotetramer and FXIII-B inhibited FXIII activation and its crosslinking function despite being directed against its noncatalytic subunit (FXIII-B).

Keywords

autoantibody - activation peptide - fibrin crosslinking - A2B2 heterotetramer - sushi domain

Authors' Contribution

A.I. created the research project and wrote and edited the manuscript. M.S. and T.O. performed experiments, wrote, and proofread the manuscript. C.Y. provided rat monoclonal antibodies against human factor XIII-B and proofread the manuscript.


Supplementary Material



Publikationsverlauf

Eingereicht: 17. Dezember 2022

Angenommen: 14. März 2023

Accepted Manuscript online:
19. März 2023

Artikel online veröffentlicht:
19. April 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Yee VC, Pedersen LC, Le Trong I, Bishop PD, Stenkamp RE, Teller DC. Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. Proc Natl Acad Sci U S A 1994; 91 (15) 7296-7300
    CrossrefPubMedGoogle Scholar
  • 2 Souri M, Kaetsu H, Ichinose A. Sushi domains in the B subunit of factor XIII responsible for oligomer assembly. Biochemistry 2008; 47 (33) 8656-8664
    CrossrefPubMedGoogle Scholar
  • 3 Ichinose A, Bottenus RE, Davie EW. Structure of transglutaminases. J Biol Chem 1990; 265 (23) 13411-13414
    CrossrefPubMedGoogle Scholar
  • 4 Takagi T, Doolittle RF. Amino acid sequence studies on factor XIII and the peptide released during its activation by thrombin. Biochemistry 1974; 13 (04) 750-756
    CrossrefPubMedGoogle Scholar
  • 5 Lorand L, Gray AJ, Brown K. et al. Dissociation of the subunit structure of fibrin stabilizing factor during activation of the zymogen. Biochem Biophys Res Commun 1974; 56 (04) 914-922
    CrossrefPubMedGoogle Scholar
  • 6 Chen R, Doolittle RF. γ-γ cross-linking sites in human and bovine fibrin. Biochemistry 1971; 10 (24) 4487-4491
    CrossrefPubMedGoogle Scholar
  • 7 McKee PA, Mattock P, Hill RL. Subunit structure of human fibrinogen, soluble fibrin, and cross-linked insoluble fibrin. Proc Natl Acad Sci U S A 1970; 66 (03) 738-744
    CrossrefPubMedGoogle Scholar
  • 8 Kimura S, Aoki N. Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor. J Biol Chem 1986; 261 (33) 15591-15595
    CrossrefPubMedGoogle Scholar
  • 9 Hethershaw EL, Cilia La Corte AL, Duval C. et al. The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis. J Thromb Haemost 2014; 12 (02) 197-205
    CrossrefPubMedGoogle Scholar
  • 10 Dorgalaleh A, Rashidpanah J. Blood coagulation factor XIII and factor XIII deficiency. Blood Rev 2016; 30 (06) 461-475
    CrossrefPubMedGoogle Scholar
  • 11 Biswas A, Ivaskevicius V, Seitz R, Thomas A, Oldenburg J. An update of the mutation profile of Factor 13 A and B genes. Blood Rev 2011; 25 (05) 193-204
    CrossrefPubMedGoogle Scholar
  • 12 Ivaskevicius V, Seitz R, Kohler HP. et al; Study Group. International registry on factor XIII deficiency: a basis formed mostly on European data. Thromb Haemost 2007; 97 (06) 914-921
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 13 Saito M, Asakura H, Yoshida T. et al. A familial factor XIII subunit B deficiency. Br J Haematol 1990; 74 (03) 290-294
    CrossrefPubMedGoogle Scholar
  • 14 Li B, Bechtler C, Jenny L, Ricklin D, Schroeder V. Exploring the function of factor XIII free B subunit: interactions with complement factors and a novel approach to identify potential binding partners. Res Pract Thromb Haemost 2022; 6 (05) e12766
    CrossrefPubMedGoogle Scholar
  • 15 Lorand L, Urayama T, De Kiewiet JW, Nossel HL. Diagnostic and genetic studies on fibrin-stabilizing factor with a new assay based on amine incorporation. J Clin Invest 1969; 48 (06) 1054-1064
    CrossrefPubMedGoogle Scholar
  • 16 Godal HC. An inhibitor to fibrin stabilizing factor (FSF, factor XIII). Scand J Haematol 1970; 7 (01) 43-48
    CrossrefPubMedGoogle Scholar
  • 17 Godal HC, Ly B. An inhibitor of activated factor XIII, inhibiting fibrin cross-linking but not incorporation of amine into casein. Scand J Haematol 1977; 19 (05) 443-448
    CrossrefPubMedGoogle Scholar
  • 18 Henriksson P, McDonagh J, Villa M. Type I autoimmune inhibitor of factor XIII in a patient with congenital factor XIII deficiency. [abstract] Thromb Haemost 1983; 50 (01) 272
    PubMedGoogle Scholar
  • 19 Seiving B, Henriksson P, Stenberg P, Nilsson IM. A reversed activity staining procedure for detection of an acquired antibody against factor XIII in a girl with factor XIII deficiency. Br J Haematol 1992; 82 (02) 414-416
    CrossrefPubMedGoogle Scholar
  • 20 Manco-Johnson M, Nuss R, Lefkowitz J, Nugent D. Characterization and quantitation of an inhibitor to the A chain of Factor XIII (FXIII) in a child with severe factor XIII deficiency. [abstract] Blood 1993; 82: 596a
    PubMedGoogle Scholar
  • 21 Huth-Kühne A, Lages P, Zimmermann R. Intracranial hemorrhage in a patient with congenital factor XIII deficiency and inhibitor – successful treatment with Ig-immunoadsorption and high dose continuous factor XIII infusion. [abstract] Blood 1998; 92: 106b
    PubMedGoogle Scholar
  • 22 Rivard GE, St Louis J, Lacroix S, Champagne M, Rock G. Immunoadsorption for coagulation factor inhibitors: a retrospective critical appraisal of 10 consecutive cases from a single institution. Haemophilia 2003; 9 (06) 711-716
    CrossrefPubMedGoogle Scholar
  • 23 Pénzes K, Vezina C, Bereczky Z. et al. Alloantibody developed in a factor XIII A subunit deficient patient during substitution therapy; characterization of the antibody. Haemophilia 2016; 22 (02) 268-275
    CrossrefPubMedGoogle Scholar
  • 24 Sosa R, Gailani D, Neff AT. Development of anti-factor XIII antibodies in a patient with hereditary factor XIII deficiency receiving therapy for chronic hepatitis C. Haemophilia 2014; 20 (06) e429-e432
    CrossrefPubMedGoogle Scholar
  • 25 Guzman MP, Alderuccio JP, Harrington T. Immunotolerance approach to refractory CNS bleeding in a patient with congenital factor XIII deficiency and acquired alloantibody. Haemophilia 2018; 24 (04) e252-e254
    CrossrefPubMedGoogle Scholar
  • 26 Karaman S, Akkaya E, Genc S. et al. Congenital factor XIII deficiency with the presence of inhibitor: a case study. J Pediatr Hematol Oncol 2021; 43 (01) e99-e102
    CrossrefPubMedGoogle Scholar
  • 27 Wada H, Souri M, Matsumoto R, Sugihara T, Ichinose A. Alloantibodies against the B subunit of plasma factor XIII developed in its congenital deficiency. Thromb Haemost 2013; 109 (04) 661-668
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 Lewis SD, Janus TJ, Lorand L, Shafer JA. Regulation of formation of factor XIIIa by its fibrin substrates. Biochemistry 1985; 24 (24) 6772-6777
    CrossrefPubMedGoogle Scholar
  • 29 Souri M, Osaki T, Ichinose A. The non-catalytic B subunit of coagulation factor XIII accelerates fibrin cross-linking. J Biol Chem 2015; 290 (19) 12027-12039
    CrossrefPubMedGoogle Scholar
  • 30 Kishiro Y, Kagawa M, Naito I, Sado Y. A novel method of preparing rat-monoclonal antibody-producing hybridomas by using rat medial iliac lymph node cells. Cell Struct Funct 1995; 20 (02) 151-156
    CrossrefPubMedGoogle Scholar
  • 31 Katona E, Pénzes K, Csapó A. et al. Interaction of factor XIII subunits. Blood 2014; 123 (11) 1757-1763
    CrossrefPubMedGoogle Scholar
  • 32 Souri M, Osaki T, Ichinose A. Anti-factor XIII A subunit (FXIII-A) autoantibodies block FXIII-A2 B2 assembly and steal FXIII-A from native FXIII-A2 B2. J Thromb Haemost 2015; 13 (05) 802-814
    CrossrefPubMedGoogle Scholar
  • 33 Lorand L, Maldonado N, Fradera J, Atencio AC, Robertson B, Urayama T. Haemorrhagic syndrome of autoimmune origin with a specific inhibitor against fibrin stabilizing factor (factor XIII). Br J Haematol 1972; 23 (01) 17-27
    CrossrefPubMedGoogle Scholar
  • 34 Lorand L, Velasco PT, Rinne JR, Amare M, Miller LK, Zucker ML. Autoimmune antibody (IgG Kansas) against the fibrin stabilizing factor (factor XIII) system. Proc Natl Acad Sci U S A 1988; 85 (01) 232-236
    CrossrefPubMedGoogle Scholar
  • 35 Fukue H, Anderson K, McPhedran P, Clyne L, McDonagh J. A unique factor XIII inhibitor to a fibrin-binding site on factor XIIIA. Blood 1992; 79 (01) 65-74
    CrossrefPubMedGoogle Scholar
  • 36 Tosetto A, Rodeghiero F, Gatto E, Manotti C, Poli T. An acquired hemorrhagic disorder of fibrin crosslinking due to IgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide. Am J Hematol 1995; 48 (01) 34-39
    CrossrefPubMedGoogle Scholar
  • 37 Lorand L, Velasco PT, Murthy SN, Lefebvre P, Green D. Autoimmune antibody in a hemorrhagic patient interacts with thrombin-activated factor XIII in a unique manner. Blood 1999; 93 (03) 909-917
    CrossrefPubMedGoogle Scholar
  • 38 Ajzner E, Schlammadinger A, Kerényi A. et al. Severe bleeding complications caused by an autoantibody against the B subunit of plasma factor XIII: a novel form of acquired factor XIII deficiency. Blood 2009; 113 (03) 723-725
    CrossrefPubMedGoogle Scholar
  • 39 Souri M, Ozawa T, Osaki T, Koyama T, Muraguchi A, Ichinose A. Cloning of human anti-factor XIII monoclonal antibody dissects mechanisms of polyclonal antibodies in a single patient. J Thromb Haemost 2023; 21 (02) 255-268
    CrossrefPubMedGoogle Scholar
  • 40 Protopopova AD, Ramirez A, Klinov DV, Litvinov RI, Weisel JW. Factor XIII topology: organization of B subunits and changes with activation studied with single-molecule atomic force microscopy. J Thromb Haemost 2019; 17 (05) 737-748
    CrossrefPubMedGoogle Scholar