Clinical Study to Determine the Pathogenesis of Autoimmune Thrombocytopenia in Pediatric Patients

Background Immune thrombocytopenia (ITP) is a common pediatric autoimmune disorder that leads to isolated thrombocytopenia due to platelet destruction and suppressed platelet production. The peak incidence is in children aged 1-6 years. Most cases of acute ITP in children are mild and self-limited, with majority of children having a spontaneous recovery with normalization of platelet counts in 3-6 months. After 12 months there remains a small proportion that develop chronic ITP. ITP occurs not only due to autoantibody mediated platelet destruction, but cellular immunity and cytokines play a major role in the development and persistence of chronic ITP. Objective The aim of this study is to determine if the immune profile of ITP patients at the time of diagnosis can help identify factors that increase an individual's risk of developing chronic ITP. Design/Method We enrolled patients with newly diagnosed ITP from 9 months to 18 years of age at Children's Hospital of Orange County. Blood samples were drawn at the time of diagnosis, at time of platelet count recovery, and when patients developed chronic ITP. Samples were sent to Stanford University Human Immune Monitoring Center (HIMC). On each sample drawn, mononuclear cell profiles were evaluated using mass cytometry (CyTOF) and cytokine levels were determined using Luminex assays. On each sample we were able to characterize 125 different parameters for mononuclear cell identification and enumeration along with 80 different cytokines. Results We collected samples from a total of ten patients. Three of ten patients went on to develop chronic ITP, which included two adolescent females, and a 2-year-old male. We previously reported that lower levels of transitional B cells and IL-10 at time of ITP diagnosis may contribute to the development of chronic ITP and persistent thrombocytopenia in this patient cohort. In addition, our study noted a difference amongst the Th17 cells. In patients who went on to develop chronic ITP, they were noted to have lower levels of Th17 CD8+ cells at the time of diagnosis when compared to patients with acute ITP. Additionally, the Th17 CD4+ to Th17 CD8+ ratio was higher at time of diagnosis in chronic ITP patients (average 3.49) compared to acute ITP patients (average 1.22). Acute ITP patients were also noted to have higher levels of IL-17 compared to the chronic ITP patients at time of diagnosis. Conclusion This study looks at an extensive profile of immune and cytokine markers in ITP. Our study shows that there are decreased levels of Th17 CD8+ cells at time of diagnosis in patients that go on to develop chronic ITP. This lower level of Th17 CD8+ in this patient group correlates with lower levels of IL-17 expression. Though our patient cohort is currently small, we are continuing to enroll at least 150 more patients to document trends and identify risk factors that increase the likelihood of a patient developing chronic ITP. We hope to personalize therapy early on for ITP patients by identifying disrupted immune pathways, thus preventing persistence of thrombocytopenia.