OC 63.5 - Cytokine profile of patients with Acquired Hemophilia A (AHA) in a longitudinal study

Tuesday, July 12, 2022

3:45 PM – 4:00 PM

Location: ExCel Center, ICC Capital Suite Room 7&12

Presentation Format: In-Person

Presenting Author(s)

Jessica O. Frade-Guanaes, MsC

Graduate student
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil

Co-Author(s)

AR

Ana P. Racanelli

Graduate student
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
LS

Lucia H. Siqueira

Biologist
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
CC

Carolina Costa-Lima

MD, MSc
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
SM

Samuel S. Medina

MD, MSc
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
NF

Nívia M. Foschi

MD
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
LD

Luiz G. R. De Lima

Undergraduate student
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
AF

Ana P. Francisco

Biologist
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
MC

Marina P. Colella

MD, PhD
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
SD

Silmara Aparecida De Lima Montalvão

Biologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
GY

Gabriela G. Yamaguti-Hayakawa

MD
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil
Margareth C. C. Ozelo, MD, PhD

Associate Professor
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
Campinas, Sao Paulo, Brazil

Background: Acquired Hemophilia A (AHA) is an autoimmune disease caused by the production of autoantibodies against factor VIII. There is limited data about the pathophysiology of the disease, including T and B cells response.

Aims: To determine the cytokine expression through T and B cells activation in a longitudinal evaluation of patients with AHA.

Methods: This study included 18 patients diagnosed with AHA from a single center. Peripheral blood mononuclear cells were isolated before immunosuppressive therapy (IST), after achieving complete remission, and at relapse/failure. Cells were cultivated with RPMI-1640 medium, with 7.5x105 cells/well in a 48-well plate. After 24h, cells were stimulated with full-length recombinant FVIII concentrate (rFVIII). After incubation for 24h, cells were analyzed by flow cytometry (FACS).

Results: IST consisted of prednisone with cyclophosphamide (72.2%), only cyclophosphamide (11.1%) and, rituximab as second-line therapy (16.7%). 50% of patients (n=9) achieved complete remission, and 27.8% (n=5) were considered as failure (2) or relapse (3). Three patients are still under initial follow-up, and one patient died and was censured for the longitudinal analysis (table 1). We observed a significant increase in the production of CD4 cytokine subsets in both responding and non-responding (failure/relapse) patients at baseline when compared with healthy individuals. This difference was not observed when patients achieved remission. Also, we observed increased production of Th17 [IL-17A (P= 0.0002), IL-21 (P=0.007), TGF-b (P=0.04)], Th2 [IL-4 (P= 0.004)] and Th1 cytokines [TNF-a (P=0.006), IFN-γ (P=0.001)] between all AHA at baseline and controls. Interestingly, as we previously reported for BAFF (B-cell activating factor), baseline levels of IFN-γ were markedly increased in non-responding patients when compared to patients with sustained complete remission (figure 1).

Conclusion(s): Our findings suggest that BAFF levels in B cells and IFN- γ in T cells at the diagnosis are potential biomarkers for AHA prognosis and treatment response.