Abstract Number: OC 63.5
Meeting: ISTH 2022 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Acquired Hemorrhagic Coagulation Disorders
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 7.5×105 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.
To cite this abstract in AMA style:
Frade-Guanaes J, Racanelli A, Siqueira L, Costa-Lima C, Medina S, Foschi N, De Lima L, Francisco A, Colella M, Montalvão S, Yamaguti-Hayakawa G, Ozelo M. Cytokine profile of patients with Acquired Hemophilia A (AHA) in a longitudinal study [abstract]. https://abstracts.isth.org/abstract/cytokine-profile-of-patients-with-acquired-hemophilia-a-aha-in-a-longitudinal-study/. Accessed September 27, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/cytokine-profile-of-patients-with-acquired-hemophilia-a-aha-in-a-longitudinal-study/