The Role of IL-23/Th17 Pathway in Patients with Primary Immune Thrombocytopenia

Abstract

BackgroundPrimary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an unclear etiology. This study aims to investigate the role of IL-23/Th17 pathway in patients with ITP.MethodThe gene expressions of IL-17, IL-23 and their receptors in ITP patients and healthy controls were analyzed by quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in plasma. Flow cytometry was used to detect the frequency of Th17 cells. The correlation between plasma IL-23 and IL-17 levels, Th17 cells, platelets were analyzed. The level of Th17-related cytokines was measured by ELISA following stimulation with IL-23. Subsequently, the IL-23 and IL-17 levels were measured in patients post-treatment.ResultsThe PBMCs of ITP patients showed increased mRNA expression levels in each of the following: IL-23p19, IL-12p40, IL-23R, IL-12Rβ1, IL-17A, IL-17F, and RORC. In addition, elevated Th17 cells and plasma IL-17, IL-23 levels were also observed in these ITP patients. Furthermore, it was found that IL-23 levels in plasma are positively correlated with IL-17 levels and Th17 cells, yet negatively correlated with platelet count. Following IL-23 stimulation in vitro, IL-17 levels showed significant elevation. Furthermore, both IL-23 and IL-17 levels decreased after effective treatment.ConclusionThe IL-23/Th17 pathway may be involved in the pathogenesis of ITP through enhancement of the Th17 response. Moreover, our results suggest that the IL-23/Th17 pathway is a potential therapeutic target in future attempts of ITP treatment.

Association of IL-17A and IL-17F Gene Polymorphisms with Acute Immune Thrombocytopenia in Egyptian Children

“…with the exception of the IL17A rs2275913 GG genotype being more closely associated with early recovery than with a persistent course of the disease (21.7% vs. 5.3%, p = 0.04). Open Journal of Blood Diseases Moreover, El Husseiny et al [23] found that IL-17 levels increased with increased Th17 cells in patients with acute ITP, which is in accordance with other studies [24] [25], and IL-17 has been shown to be down regulated following immunosuppressive therapy [25]. Furthermore, Okamoto et al [26] demonstrated that the response to Eltrombopag, a drug used for thrombocytopenia, is significantly better in patients with low IL-17 expression, indicating that patients with ITP who achieve early remission may have low IL-17 levels [26].…”

Immune Thrombocytopenia. Egyptian Experience With Study of Il-17, Tgfb, Cytokines in Chronic and Persistent Immune Thrombocytopenia Patients.

“…Regarding IL-17, it was found increased with T helper 17 in both recent and reactive ITP. [10] and After the treatment with immunosuppressive therapy, IL-17 was down-regulated. [11] While in chronic ITP, Hunag et al found IL-17 to be same to that of normal controls.…”

The Centenary of Immune Thrombocytopenia – Part 1: Revising Nomenclature and Pathogenesis

“…Thus, while Treg cells play a fundamental role in the maintenance of immune tolerance to prevent autoimmune disease, Th17 cells play the opposite role. Indeed, it has been demonstrated that Th17 cells are more potent than Th1 cells in inducing autoimmune disorders ( 111 – 113 ). Several reports support a role for IL17 in the pathogenesis of ITP.…”