Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome – characterization of the antibody

Abstract

HungaryTo cite this article: P enzes K, R azs o K, Katona E, Ker enyi A, Kun M, Muszbek L. Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome -characterization of the antibody. J Thromb Haemost 2016; 14:1517-20. Essentials• Autoantibody against factor XIII (FXIII) is a rare but severe acquired hemorrhagic diathesis.• In an elderly patient, anti-FXIII-A antibody led to severe bleedings with fatal outcome.• The neutralizing autoantibody bound to FXIII with high affinity (Ka%10).• The dominant effect of the autoantibody was the inhibition of activated FXIII.Summary. Autoantibodies may develop against the catalytic A subunit of factor XIII (FXIII-A) or the carrier B subunit (FXIII-B). Autoimmune FXIII-A deficiency was diagnosed in an elderly (75 years) patient with severe bleeding symptoms. The patient had 3% FXIII activity, and unmeasurable FXIII-A 2 B 2 and FXIII-A antigens in the plasma, whereas, in the platelet lysate, activity and FXIII-A antigen values were normal. As revealed by western blotting, FXIII antigen was present in the plasma, but the autoantibody interfered with the immunoassays. A mixing study indicated the presence of inhibitor with a titer of 63.2 Bethesda units (BU). The patient's IgG bound to FXIII-A 2 B 2 and to FXIII-A 2 with equally high affinity (K a in the range of 10 9 M À1). It exerted a multiple inhibitory effect on FXIII activation/ activity (IC50: 50 lg mL À1 ). Immunosupressive therapy gradually decreased the autoantibody titer to 8.0 BU, but FXIII activity remained very low, and, owing to recurrent bleeding, the patient died.

Auto‐ and alloantibodies against factor XIII: laboratory diagnosis and clinical consequences

“…Figure (A) demonstrates the marked inhibitory effect of an alloantibody . In another study an anti‐FXIII‐A autoantibody only slightly affected the truncation of FXIII‐A , whereas in a third case the autoantibody failed to influence the release of AP‐FXIII by thrombin .…”

“…In case 1 both Ca 2+ ‐induced FXIII‐A 2 ’B 2 activation and FXIIIa were inhibited to a considerable extent by an alloantibody (multiple inhibition). In case 2 the full inhibitory effect of an autoantibody was a result of the inhibition of FXIIIa (type II antibody), whereas in case 3 a moderate inhibition of Ca 2+ ‐induced FXIII‐A 2 ’B 2 activation also contributed to the full inhibitory effect.…”

“…IgG was prepared from the plasma of a patient with anti‐ FXIII ‐A autoantibody. FXIII was pre‐incubated with various concentrations of the patient's IgG and then it was activated by thrombin and Ca 2+ and the transglutaminase activity was measured .…”

“…Normal IgG had no effect on FXIII activity, and the IC50 value for the patient's IgG could be calculated (an IC50 tool kit is useful for the calculation; http://www.ic50.tk). A typical IC50 curve is shown in Fig. (B).…”

“…Measured FXIII activities were expressed as percentage of FXIII activity measured in the absence of the antibody (relative FXIII activity). The data shown on the graph were calculated from the results published in references .…”