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Alloantibody developed in a factor XIII A subunit deficient patient during substitution therapy; characterization of the antibody
- Source :
- Haemophilia : the official journal of the World Federation of Hemophilia. 22(2)
- Publication Year :
- 2015
-
Abstract
- Introduction In factor XIII A subunit (FXIIIA) deficiency, the development of alloantibodies is extremely rare. Only four reports have been published and the antibodies were not characterized. Aim The aim of this study was to describe the clinical course and the laboratory diagnosis of a FXIII-A deficient patient who developed alloantibodies. Methods FXIII activity was assessed with an ammonia release assay. FXIII-A, FXIII B subunit (FXIII-B) and the complex plasma FXIII (FXIII-A2B2) antigens were determined by ELISA. The causative mutation was detected by fluorescent DNA sequencing. The binding of alloantibody to FXIII-A2 and FXIII-A2B2 was studied by surface plasmon resonance. The cleavage of FXIII-A by thrombin and Ca2+-induced activation of thrombin-cleaved FXIII were followed by western blotting and activity measurement, respectively. Results FXIII activity, FXIII-A2B2 and FXIII-A antigens were below the limit of detection in the patient's plasma. The severe FXIII-A deficiency was due to a novel homozygous mutation resulting in early stop codon (c.127C>T, p.Gln42STOP). The alloantibody bound to FXIII-A2 and FXIII-A2B2 with equally high affinity (Kd~10−8). It accelerated the elimination of administered FXIII concentrate from the circulation, interfered with thrombin and Ca2+-induced activation and inhibited FXIII activity. Attempts to eliminate the alloantibody resulted only in transient improvement. Patient developed intracerebral haemorrhage after a minor trauma and died in spite of aggressive replacement therapy with FXIII concentrate. Conclusion The anti-FXIII-A alloantibody caused an unmanageable bleeding complication. The antibody was of combined subtype which accelerated the elimination of FXIII and exerted a multiple inhibitory effect on FXIII activation/activity.
- Subjects :
- biology
business.industry
Protein subunit
Orvostudományok
Hematology
General Medicine
030204 cardiovascular system & hematology
medicine.disease
Factor XIII
Stop codon
Bleeding diathesis
Blot
03 medical and health sciences
0302 clinical medicine
Thrombin
Antigen
Immunology
medicine
biology.protein
Elméleti orvostudományok
Antibody
business
Genetics (clinical)
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 13652516
- Volume :
- 22
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Haemophilia : the official journal of the World Federation of Hemophilia
- Accession number :
- edsair.doi.dedup.....fad2bdbf3c82720506a4cc07834b64c6