Anwar A Sayed
Imperial College London, United Kingdom
Title: Immune Thrombocytopenia (ITP) pathogenesis and treatment: More than meets the eyes
Biography
Biography: Anwar A Sayed
Abstract
Immune Thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated low platelet count. It was thought to be primarily due to autoantibody against platelets. However, the absence of detectable autoantibodies in over 30% of patients and their unresponsiveness to B-cell-targeting therapy suggested an active role for T cells. Studies have confirmed the proinflammatory nature of ITP characterized as Th1/Th17 profile. However, little is known about the involvement of CD8+ Cytotoxic T cells (CTL) in ITP pathophysiology and whether they are regulated by regulatory T cells (Treg). Immunosuppressive therapy has been the mainstay treatment in ITP. More recently, Thrombopoietin Receptor Agonists (TPORA); Romiplostim
(Romi) and Eltrombopag (EPAG) have been increasingly used to stimulate megakaryocytopoiesis to produce more platelets. TPO-RAs are reported to induce complete remission in up to 30% of cases with limited understanding of their impact on the immune system. Here we describe changes in T cell subsets, particularly CTL and Tregs in patients with ITP: How these
changes are affected by disease activity and how TPO-RA may induce remission through modulating the immune system. Multi-color flow cytometric panels were designed to characterize peripheral blood T cell subsets phenotypically as well as functionally through intracellular cytokine expression. Forty (40) patients with ITP were studied and compared with 26 age and gender matched Healthy Controls (HC). Terminally-differentiated effector CTLs were significantly higher in patients compared to HC. This effector population is polyfunctional, expressing high levels of proinflammatory cytokines compared to HC. Although Treg functionality was preserved in these patients, they corresponded to disease activity and in relation to CTLs. Romi and EPAG demonstrate differential T-cell changes which also impacted the disease activity. While Th1/Th2-cell ratio is
considered as driving ITP, these results highlight the role of cytokine-secreting CTLs in the disease pathogenesis, as well as suggesting an immunomodulatory mechanism of these TPO-RAs.