Severe bleeding diatheses in an elderly patient with combined type autoantibody against factor XIII A subunit; novel approach to the diagnosis and classification of anti-factor XIII antibodies

M. Kun, N. Szuber, E. Katona, K. Pénzes, A. Bonnefoy, B. Bécsi, F. Erdődi, G. E. Rivard, L. Muszbek

Research output: Contribution to journalArticle

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Abstract

Introduction: Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task. Aim: Introduction of novel approaches into the diagnosis and characterization of anti-FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency. Methods: Factor XIII activity, FXIII antigen levels and the titre of anti-FXIII-A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII-A2B2 complex, total and free FXIII-B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII-A2 (rFXIII-A2) and FXIII-A2B2 was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50% inhibition of FXIII activation/activity (IC50). The truncation of FXIII-A by thrombin was monitored by western blotting. The inhibition of Ca2+ -induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay. Results: The antibody bound to rFXIII-A2 and FXIII-A2B2 with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL−1 indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated. Conclusion: The anti-FXIII-A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody.

Original languageEnglish
Pages (from-to)590-597
Number of pages8
JournalHaemophilia
Volume23
Issue number4
DOIs
Publication statusPublished - Jul 1 2017

Fingerprint

Factor XIII
Disease Susceptibility
Autoantibodies
Hemorrhage
Antibodies
Factor XIII Deficiency
Inhibitory Concentration 50

Keywords

  • acquired FXIII deficiency
  • antibody classification
  • autoantibody
  • binding affinity
  • bleeding diathesis
  • factor XIII

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Severe bleeding diatheses in an elderly patient with combined type autoantibody against factor XIII A subunit; novel approach to the diagnosis and classification of anti-factor XIII antibodies. / Kun, M.; Szuber, N.; Katona, E.; Pénzes, K.; Bonnefoy, A.; Bécsi, B.; Erdődi, F.; Rivard, G. E.; Muszbek, L.

In: Haemophilia, Vol. 23, No. 4, 01.07.2017, p. 590-597.

Research output: Contribution to journalArticle

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abstract = "Introduction: Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task. Aim: Introduction of novel approaches into the diagnosis and characterization of anti-FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency. Methods: Factor XIII activity, FXIII antigen levels and the titre of anti-FXIII-A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII-A2B2 complex, total and free FXIII-B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII-A2 (rFXIII-A2) and FXIII-A2B2 was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50{\%} inhibition of FXIII activation/activity (IC50). The truncation of FXIII-A by thrombin was monitored by western blotting. The inhibition of Ca2+ -induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay. Results: The antibody bound to rFXIII-A2 and FXIII-A2B2 with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL−1 indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated. Conclusion: The anti-FXIII-A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody.",
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T1 - Severe bleeding diatheses in an elderly patient with combined type autoantibody against factor XIII A subunit; novel approach to the diagnosis and classification of anti-factor XIII antibodies

AU - Kun, M.

AU - Szuber, N.

AU - Katona, E.

AU - Pénzes, K.

AU - Bonnefoy, A.

AU - Bécsi, B.

AU - Erdődi, F.

AU - Rivard, G. E.

AU - Muszbek, L.

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N2 - Introduction: Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task. Aim: Introduction of novel approaches into the diagnosis and characterization of anti-FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency. Methods: Factor XIII activity, FXIII antigen levels and the titre of anti-FXIII-A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII-A2B2 complex, total and free FXIII-B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII-A2 (rFXIII-A2) and FXIII-A2B2 was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50% inhibition of FXIII activation/activity (IC50). The truncation of FXIII-A by thrombin was monitored by western blotting. The inhibition of Ca2+ -induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay. Results: The antibody bound to rFXIII-A2 and FXIII-A2B2 with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL−1 indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated. Conclusion: The anti-FXIII-A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody.

AB - Introduction: Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task. Aim: Introduction of novel approaches into the diagnosis and characterization of anti-FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency. Methods: Factor XIII activity, FXIII antigen levels and the titre of anti-FXIII-A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII-A2B2 complex, total and free FXIII-B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII-A2 (rFXIII-A2) and FXIII-A2B2 was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50% inhibition of FXIII activation/activity (IC50). The truncation of FXIII-A by thrombin was monitored by western blotting. The inhibition of Ca2+ -induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay. Results: The antibody bound to rFXIII-A2 and FXIII-A2B2 with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL−1 indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated. Conclusion: The anti-FXIII-A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody.

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KW - bleeding diathesis

KW - factor XIII

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