Predominant anti-inflammatory immune response profile in patients with severe hemophilia A

M BELÉN IRIGOYEN; MIGUEL DE TEZANOS PINTO; BARBARA REARTE; MARTA FELIPPO; NORA V. GALASSI; DANIELA NEME; MARÍA M. E. DE BRACCO

Orlando

Congreso; World Congress; 2016

World Federation of Hemophilia

Introduction and Objectives: Patients with severe hemophilia A (SHA) may develop anti factor VIII antibodies that interfere with Factor VIII replacement treatment. Antibodies belonging to the IgG4 subclass predominate in those with high inhibitory titers, but the mechanisms involved in this response are not clear. The aim of this study was to study the conditions that lead to this type of antibody response. We evaluated the Th1/Th2 profile, the role of follicular T lymphocytes (TFH) involved in the generation of the humoral immune response and the cytokine milieu (IL-10 and IL-21) that favor it.Material and Methods: Twenty patients with SHA were included (10 with inhibitory antibodies (I) and 10 with undetectable I (non-I). Controls were 12 normal donors (N). Peripheral blood TFH were studied by flow cytomery, using CXCR5, CCR7 and PD-1 to define subpopulations within the CD4 compartment. Intracellular cytokines (IFN-γ, IL-4, IL-10 and IL-21 were assayed in lymphocytes stimulated with phorbol myristic acid (PMA) and ionomycine. Results: While the overall % of TFH was similar in the three groups, expression of PD-1 was significantly higher and that of CCR7 was lower in I when compared to non-I and N, *p