Expansion of Circulating Follicular Helper T cells and their Phenotypes in Immune Thrombocytopenic Purpura and their Relation to Disease Outcome

Abstract

Background: Immune thrombocytopenia (ITP) is an autoimmune mediated disease, which lead to antibody induced platelets destruction. Among different immune mechanisms, Humoral contribute much in ITP pathogenesis. This is through complex interaction between antigen-presenting cells, T helper cells, regulatory T cells and B cells. Circulating T follicular helper (cTFH) cells play a very significant role in autoimmune diseases. However, it remains unclear in ITP. Aim: The current study was designed to find the possible role of circulating TFH, their phenotypes and cytokine profile (IL-21, IL-17 and IL-10) in the pathogenesis and outcome of ITP patients. Patient and methods: Twenty five age and sex matched healthy control and forty eight patients with chronic ITP were included; clinical examination and routine laboratory investigations were done. Serum cytokine levels (IL-10, IL-17, IL-21), estimation of reticulated platelets (RP) and flow cytometric analysis of circulating TFH (CXCR5CD4+) and their phenotypes (ICOS+/ and PD-1+). Results: RP and cytokine levels were higher in ITP patients compared to control group. The frequency of cTFH cells and its phenotypes (ICOS+/and PD-1+)is significantly higher in chronic ITP patients compared to healthy controls, however, CD3+, CD4+ and CD8+ cells were not significantly different. A positive correlation was observed between TFH cells and each of clinical manifestations, presence of platelet antibody, cytokine levels and (ICOS +/and PD-1+) expression in ITP patients. After receiving immunotherapy, serum IL-10, IL17 and IL-21, as well as the frequency of cTFH cells, and its phenotypes were measured. Conclusion: TFH cells and their subtypes probably are implicated in autoimmunity. In ITP their numbers are increased furthermore, the immunotherapy resulted in reduction of TFH cells and their producing cytokines. Therefore, TFH cell and associated important molecules could constitute a new therapeutic modality, aiming at reducing TFH cell generation. This will lead to ameliorate disease