Cloning of human anti-factor XIII monoclonal antibody dissects mechanisms of polyclonal antibodies in a single patient.

Male Humans Aged, 80 and over Antibodies, Monoclonal Factor XIII / chemistry Factor XIIIa Autoantibodies Factor XIII Deficiency / diagnosis Fibrin Cloning, Molecular
acquired bleeding disorder autoimmune coagulation factor deficiency human monoclonal antibody neutralizing antibody nonneutralizing antibody

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
02 2023
Historique:
received: 21 07 2022
revised: 28 10 2022
accepted: 13 11 2022
pubmed: 27 1 2023
medline: 15 2 2023
entrez: 26 1 2023
Statut: ppublish

Résumé

Coagulation factor XIII (FXIII) consists of 2 A (FXIII-A) and 2 B (FXIII-B) subunits that cross-link and strengthen the hemostatic fibrin thrombus; thus, abnormal bleeding occurs when FXIII is significantly reduced. Autoimmune-acquired FXIII deficiency (AiF13D) is characterized by lethal bleeding secondary to the development of autoantibodies against FXIII. However, since anti-FXIII autoantibodies are polyclonal, the mechanism underlying FXIII dysfunction is unclear. The objective of this study was to dissect the inhibitory mechanisms of polyclonal anti-FXIII autoantibodies. In this study, we prepared the human monoclonal antibodies (hmAbs) from the peripheral blood of an 86-year-old man with AiF13D by using a new complementary DNA cloning method and analyzed the properties of each autoantibody. Seventeen clones obtained from hmAbs were divided into the following 3 groups: dissociation inhibitors of FXIII-A Cloning of anti-FXIII autoantibodies enabled us to not only elucidate the mechanism and pathophysiology of AiF13D but also develop a completely new type of anticoagulant.

Sections du résumé

BACKGROUND
Coagulation factor XIII (FXIII) consists of 2 A (FXIII-A) and 2 B (FXIII-B) subunits that cross-link and strengthen the hemostatic fibrin thrombus; thus, abnormal bleeding occurs when FXIII is significantly reduced. Autoimmune-acquired FXIII deficiency (AiF13D) is characterized by lethal bleeding secondary to the development of autoantibodies against FXIII. However, since anti-FXIII autoantibodies are polyclonal, the mechanism underlying FXIII dysfunction is unclear.
OBJECTIVES
The objective of this study was to dissect the inhibitory mechanisms of polyclonal anti-FXIII autoantibodies.
METHODS
In this study, we prepared the human monoclonal antibodies (hmAbs) from the peripheral blood of an 86-year-old man with AiF13D by using a new complementary DNA cloning method and analyzed the properties of each autoantibody.
RESULTS
Seventeen clones obtained from hmAbs were divided into the following 3 groups: dissociation inhibitors of FXIII-A
CONCLUSION
Cloning of anti-FXIII autoantibodies enabled us to not only elucidate the mechanism and pathophysiology of AiF13D but also develop a completely new type of anticoagulant.

Identifiants

DOI: 10.1016/j.jtha.2022.11.019 PMID: 36700504
pubmed: 36700504
pii: S1538-7836(22)07633-4
doi: 10.1016/j.jtha.2022.11.019
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Factor XIII 9013-56-3
Factor XIIIa EC 2.3.2.13
Autoantibodies 0
Fibrin 9001-31-4

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

255-268

Informations de copyright

Copyright © 2022. Published by Elsevier Inc.

Auteurs

Masayoshi Souri (M)

Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan; The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare, Tokyo, Japan; Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, 2-2-2, Iida-Nishi, Yamagata, Japan.

Tatsuhiko Ozawa (T)

Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Tsukasa Osaki (T)

Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan; The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare, Tokyo, Japan.

Takatoshi Koyama (T)

Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan.

Atsushi Muraguchi (A)

Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Akitada Ichinose (A)

Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan; The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare, Tokyo, Japan. Electronic address: aichinos@med.id.yamagata-u.ac.jp.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur XIII › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur XIII › Facteur XIIIa › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Autoanticorps › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Troubles héréditaires de la coagulation sanguine › Déficit en facteur XIII › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Fibrine › Cloning of human anti-factor XIII monoclonal...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Clonage moléculaire › Cloning of human anti-factor XIII monoclonal...