Novel Immunochromatographic Test for Anti-factor XIII B Subunit Autoantibodies to Diagnose Autoimmune Acquired Factor XIII Deficiency

Tsukasa Osaki; Chikako Yokoyama; Yasuo Magari; Masayoshi Souri; Akitada Ichinose

doi:10.1055/a-2061-3182

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2023; 123(08): 793-803
DOI: 10.1055/a-2061-3182

New Technologies, Diagnostic Tools and Drugs

Novel Immunochromatographic Test for Anti-factor XIII B Subunit Autoantibodies to Diagnose Autoimmune Acquired Factor XIII Deficiency

Authors

Tsukasa Osaki

¹Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan

²The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan

³Department of Public Health and Hygiene, Yamagata University School of Medicine, Yamagata, Japan
Chikako Yokoyama

⁴Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Japan

⁵Department of Chemistry and Bioengineering, Graduate School of Engineering, Osaka Metropolitan University, Osaka, Japan
Yasuo Magari

⁶Q-may Laboratory Corporation, Oita, Japan
Masayoshi Souri

¹Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan

²The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan

³Department of Public Health and Hygiene, Yamagata University School of Medicine, Yamagata, Japan
Akitada Ichinose

¹Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan

²The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan

Abstract

Autoimmune factor XIII (FXIII) deficiency (AiF13D) is an acquired life-threatening bleeding disorder due to anti-FXIII autoantibodies (autoAbs). We previously established an immunochromatographic test (ICT) for detection of anti-FXIII-A subunit (FXIII-A) autoAbs. Conversely, the detection of anti-FXIII-B subunit (FXIII-B) autoAbs is currently performed in a limited number of medical facilities through time-consuming and expensive laboratory tests, such as dot-blotting analysis and enzyme-linked immunosorbent assay (ELISA). Accordingly, in this study, we generated eight rat monoclonal antibodies (mAbs) against human FXIII-B using the rat lymph node method. By employing an ELISA, two mAbs, 2G12B10 and 8H12B9, were selected considering the distance between the recognition regions of each mAb (the 6th and 9th–10th Sushi domain, respectively) and the strength of their reactivity. Using this mAb combination, we prototyped an ICT to detect anti-FXIII-B autoAbs and distinguish between AiF13D and “nonimmune” acquired FXIII deficiency (acF13D), and tested it with 22 healthy controls, 23 acF13D patients, 15 AiF13D patients without anti-FXIII-B autoAbs, and 8 AiF13D patients with anti-FXIII-B autoAbs. Receiver operating characteristic curve analyses of ICTs for anti-FXIII-B autoAbs were performed and revealed a precision similar to dot-blot analysis. Human anti-FXIII-A mAbs were also generated from a single patient with AiF13D using a new cDNA cloning method, and their binding properties were characterized. Consequently, anti-FXIII-A immunoglobulin G preparations were established as potentially permanent positive controls of ICT for anti-FXIII-A antibodies. Combining the previously developed ICT for anti-FXIII-A autoAbs and the novel ICT for anti-FXIII-B autoAbs may reduce false negatives and lead to appropriate diagnosis and treatment.

Keywords

bleeding disorder - autoimmune coagulation factor deficiencies - autoantibody - immunochromatography - point-of-care-tests

Full Text

References

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