Profiling of Anti-FVIII Antibodies in Acquired Haemophilia A: 'Insights into Domain Specificity, Isotype Variability, and Clinical Correlations'.

INTRODUCTION

Acquired haemophilia A (AHA) is a rare autoimmune disorder caused by autoantibodies against coagulation factor VIII (FVIII), resulting in significant bleeding risks.

AIM

To characterize the anti-FVIII antibody profile in AHA patients by assessing isotypes, subclasses, and correlations with key clinical parameters.

METHODS

Eighty AHA patients were retrospectively analysed by assessing FVIII inhibitor levels, antibody isotypes (IgG, IgA, IgM), IgG subclasses, and domain specificity using a bead-based assay. Clinical data were correlated with antibody profiles. IgG domain profiles were compared with a congenital haemophilia A (CHA) cohort.

RESULTS

The cohort had a median age of 74 years, with 60% males. Idiopathic cases accounted for 67%, and 17% had bleeding linked to medical interventions. Major bleeding sites were musculoskeletal/retroperitoneal (45%) and skin (36%). Within six months, 18% of patients died, mostly from sepsis. Anti-FVIII IgG antibodies were present in all patients, with IgG (96%) and IgG (60%) being the most common subclasses. IgM and IgA anti-FVIII antibodies were detected in 17.5% and 18.8% of patients, respectively, with IgM positivity associated with higher mortality (33%). IgG subclass correlated significantly with inhibitor titres (r = 0.54; p < 0.001). Compared to CHA, AHA showed a higher prevalence of C1C2 domain-targeting antibodies (49% vs. 77%), associated with NBA levels (r = 0.51; p < 0.001).

CONCLUSION

Anti-FVIII antibody profiling reveals distinct patterns in AHA, with IgG linked to higher inhibitor levels. The C1C2 domain specificity of the anti-FVIII antibodies suggests a potential role of this FVIII domain in the immunopathology of AHA patients, warranting further investigation to improve prognostic tools.