IgG subclasses of FVIII inhibitors in an argentine cohort of severe hemophilia A patients: Analysis by flow cytometry

NORA GALASSI; MARTA FELIPPO; M MARTA DE E DE BRACCO; MIGUEL CANDELA; LAURA PRIMIANI; MARÍA BELÉN IRIGOYEN

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2017 vol. 39 p. 569 - 576

1751-5521

Introduction: FVIII inhibitors consist of a polyclonal population of antibodies. Previous studies have demonstrated different distribution of IgG subclasses. IgG4 was associated to high level of FVIII inhibitors and failure of Immune Tolerance Induction (ITI) treatment. This study monitored the relative distribution of IgG subclasses of anti-FVIII in Severe Hemophilia A (SHA) patients. Methods: Anti-FVIII antibodies were measured employing an immunomethod, developed in our laboratory, that combines Flow Cytometry (FC) with microspheres coupled (FVIII-m) or not (Control-m) to FVIII. Seventy five SHA patients were studied, 17 without inhibitors (Group I); 58 with inhibitor history, 13 Low Responders (LR: Group II) and 45 High Responders (HR: Group III). Eight patients undergoing ITI were also included. Results: We found anti-FVIII antibodies in 11/27 patients (40%) without inhibitors and in 45/48 with inhibitors at the moment of the study. IgG4 was predominant only in the Group III: p=0.02 in patients with low level of inhibitors and p=0.0001 with high titer of inhibitors. Longitudinal analysis performed on patients undergoing ITI showed a gradual decrease of IgG4 values that was associated to improvement of clinical parameters during treatment. Conclusion: Regarding to these results we suggest to employ FC method supplementing functional traditional assay to improve the management of SHA patients.