Project Details

Developing a Diagnostic Test for Pediatric Immune Cytopenias

Emily Harris, MD

Summary

BACKGROUND: Evans syndrome (ES) is a life-threatening disorder resulting in autoimmune destruction of at least two hematopoietic cell lineages and a mortality rate of 36%. Other immune cytopenias, such as autoimmune hemolytic anemia (AIHA), are limited to a single lineage. There is no way to know whether an immune cytopenia will progress to ES. GAP: There are no available tests distinguish ES from other immune cytopenias, necessitating empiric treatment and a ‘watch and wait’ approach for a disease with 36% mortality. HYPOTHESIS: Test the hypothesis that increased CXCR3–CCR6+ cTfm cells and increased CXCR3+CCR6+ cTfm cells are sensitive and specific markers for AIHA and ES, respectively. We aim to correlate disease type and activity with cTfm phenotypes. METHODS: In year 1, we will enroll 50 patients with ES, 50 with AIHA, and 100 controls. Based on Fig. 1A, B, this sample size has 95% power to detect increased CXCR3–CCR6+ cTfm (Cohen’s d=1.19) in AIHA and increased CXCR3+CCR6+ (Cohen’s d=1.02) in ES ( error 0.05). Follow-up studies will be done through year 2, every 3 months as part of routine clinical evaluations. Clinical data includes: demographics, disease course, clinical blood counts and immunophenotyping, treatments and clinical response. Expression of CXCR3-CCR6+ or CXCR3+CCR6+ will be measured on CD4+CXCR5+ cells using flow cytometry of whole blood. RESULTS: Pending. IMPACT: Our prior work has enabled the development of cTfh cells into a clinical test for multisystem autoimmunity. We anticipate that the proposed studies will enable establishment of cTfm17 and cTfm1/17 T cells as diagnostic tests for immune cytopenias.