PB0178 - High plasma levels of IgG4 anti-FVIII is the hallmark of immune tolerance failure in patients with hereditary hemophilia A: results from the BrazIT Study

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Daniel G. Chaves, Msc, PhD

Researcher
Fundação Centro de Hematologia e Hemoterapia de Minas Gerais (Hemominas), Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil

Co-Author(s)

Ricardo M. Camelo, MD, MSc, MBA

Physician
Faculty of Pharmacy, Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, Brazil
BA

Brendon Ayala

Researcher
Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil
LE

Leina Y. Etto

Researcher
Centro de Hematologia e Hemoterapia da Paraíba (Hemoíba), Paraíba, Brazil
João Pessoa, Paraiba, Brazil
Ad

Andrea G. de Oliveira

Researcher
Fundação Centro de Hematologia e Hemoterapia de Minas Gerais (Hemominas), Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil
VF

Vivian K B Franco

Researcher
Centro de Hematologia e Hemoterapia de Santa Catarina (Hemosc), Santa Catarina, Brazil
Florianópolis, Santa Catarina, Brazil
MR

Maria do Rosário F. Roberti

Researcher
Centro de Hematologia e Hemoterapia de Goiás (Hemogo), Goiás, Brazil
Goiânia, Goias, Brazil
MC

Maria Aline F. Cerqueira

Researcher
Centro de Hematologia e Hemoterapia do Piauí (Hemopi), Piauí, Brazil
Teresina, Piaui, Brazil
RR

Rosângela A. Ribeiro

Researcher
Centro de Hematologia e Hemoterapia do Ceará (Hemoce), Ceará, Brazil
Fortaleza, Ceara, Brazil
FC

Fábia M R A Callado

Researcher
Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope), Pernambuco, Brazil
Recife, Pernambuco, Brazil
TA

Tânia H. Anegawa

Researcher
Centro Regional de Hematologia e Hemoterapia de Londrina, Paraná, Brazil
Londrina, Parana, Brazil
MC

Mônica H. Cerqueira

Researcher
Instituto de Hematologia do Estado do Rio de Janeiro (Hemorio), Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
SR

Suely M. Rezende

Researcher
Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil
Belo Horizonte, Minas Gerais, Brazil

Background: Immune tolerance induction (ITI) eradicates anti-factor VIII (FVIII) inhibitors in about 70% of patients with inherited hemophilia A (PwHA). Of all immunoglobulins (Ig), anti- FVIII IgG4 is known to correlate with inhibitor titre. Therefore, we hypothesized that it could be a biomarker of ITI outcome.

Aims: To evaluate the association of IgG4 anti-FVIII levels with the outcome of ITI in patients with severe hemophilia A (FVIII < 2%) with high response inhibitors.

Methods: We included PwHA who completed ITI from nine hemophilia centers. ELISA was used to detect specific IgG4 anti-FVIII in plasma samples from all patients after ITI conclusion. Most patients (66.7%) were treated with a low-dose regimen (50 international units [IU] of FVIII concentrate per kilogram 3 times weekly). ITI outcome was defined as total/partial success and failure, based on inhibitor levels and FVIII pharmacokinetics. Comparison of IgG4 anti-FVIII levels was performed using Mann Whitney test. ROC curve analysis was performed to calculate sensitivity and specificity of the ELISA. The study was approved by Ethical Committees and all participants/guardians signed a consent form.

Results: A total of 50 PwHA who completed ITI were included. Levels of IgG4 anti-FVIII were significantly higher in patients who failed ITI (median OD, 2.18; IQR 1.69-2.44) compared with those who had partial (median OD, 0.15; IQR 0.05-0.52) and complete success (median OD, 0.05; IQR 0.00-0.14) (p < 0.0001 for both). There was no difference of anti-FVIII IgG4 levels in patients with total and partial success (p = 0.07). Considering the OD cut-off of 0.62, the test had a sensitivity of 93.8% and a specificity of 82.4% for ITI failure.

Conclusion(s): PwHA who had total and partial success on ITI presented similar levels of IgG4 anti-FVIII in plasma. High levels of plasma IgG4 anti-FVIII is a hallmark of ITI failure.