Development of anti‐factor <scp>XIII</scp> antibodies in a patient with hereditary factor <scp>XIII</scp> deficiency receiving therapy for chronic hepatitis C

Sosa, R.; Gailani, David; Neff, Anne T.

doi:10.1111/hae.12537

Cited by 2 publications

(2 citation statements)

References 9 publications

(17 reference statements)

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“…Previously reported anti-FXIII-A antibodies, including allo-and auto-Abs, are catalytic FXIII inhibitors. [15][16][17][18][19][20][21][22][23][24][25][26][32][33][34][35][36][37] There have been few studies on anti-FXIII-B antibodies, 31,32,38 which did not mention their inhibitory effects on the catalytic function of FXIII; however, one anti-FXIII-B mAb was found to inhibit heterotetramer assembly. 31 To our knowledge, our current study is the first to report that anti-FXIII-B allo-Abs "indirectly" affect the crosslinking function of FXIII by blocking the FXIII-B role in anchoring FXIII A 2 B 2 on fibrinogen despite they do not target the active site of FXIII.…”

Section: Discussionmentioning

confidence: 99%

“…Although allo-Abs to FXIII are rare, anti-FXIII-A allo-Abs have been reported in at least 10 patients. [15][16][17][18][19][20][21][22][23][24][25][26] Contrastingly, to our knowledge, only one Japanese male patient with hereditary FXIII-B deficiency has been reported to develop anti-FXIII-B allo-Abs after therapeutic FXIII infusion. 27 We previously reported no inhibition of amine incorporation activity in a five-step cross-mixing test between the patient's and normal control plasma, which indicated a factor-deficient pattern.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies against Noncatalytic B Subunit of Factor XIII Inhibit Activation of Factor XIII and Fibrin Crosslinking

et al. 2023

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Background: Coagulation factor XIII (FXIII) is a proenzyme of plasma transglutaminase. It comprises two catalytic A subunits (FXIII-A) and two carrier B subunits (FXIII-B). We previously reported that alloantibodies against FXIII-B could promote FXIII clearance in a patient with congenital FXIII-B deficiency who had received infusions of plasma-derived human FXIII (A2B2 heterotetramer). Objectives: We aimed to investigate whether anti-FXIII-B antibodies affect the catalytic function of FXIII. Methods: FXIII activation and fibrin crosslinking were examined in the presence of patient plasma, isolated patient IgG, or rat anti-FXIII-B monoclonal antibodies. Results: Alloantibody levels were increased by repeated infusions of plasma-derived A2B2 heterotetramer, which enhanced binding to the functionally important FXIII-B Sushi domains. The patient plasma strongly inhibited cleavage of the FXIII-A activation peptide, amine incorporation, and fibrin crosslinking in normal plasma. Further, anti-FXIII-B alloantibodies blocked the formation of the complex of FXIII-B with FXIII-A, and fibrinogen. Rat monoclonal antibodies against the 10th Sushi domain of FXIII-B inhibited the incorporation of FXIII-B to fibrin, FXIII activation (i.e., cleavage of FXIII-A activation peptide), and ultimately fibrin crosslinking in normal plasma, independent of their effect on heterotetramer assembly with FXIII-A. Alloantibody binding to the A2B2 heterotetramer blocked the access of thrombin to the FXIII-A cleavage site, as indicated by the reaction of the alloantibodies to the A2B2 heterotetramer and FXIII-B, but not to FXIII-A. Conclusion: Anti-FXIII-B antibodies binding to the A2B2 heterotetramer and FXIII-B inhibited FXIII activation and its crosslinking function despite being directed against its non-catalytic subunit (FXIII-B).

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