WIP 152 - Differentiating primary and secondary T cell disorders using multiparametric flow cytometry

Poster Number: WIP 152
Publication Number: WIP 152.2581

Background: T cells are a critical component of the immune system, and perturbations in T cell subsets can be observed in the setting of inborn errors of immunity (primary T cell defect), as well as in secondary T cell disorders such as malignancy, autoimmunity, and infection. While genetic testing provides a definitive method for diagnosing primary T cell defects, clinical utility is hampered by slow turnaround time. Multiparametric flow cytometry facilitates rapid and detailed T cell phenotyping, however its utility in differentiating primary from secondary T cell disorders is not well defined.

Objective: 1) Analyze the frequency and proportions of T cell subsets in individuals with suspected or confirmed primary and secondary T cell disorders; 2) Determine whether abnormalities in specific T cell subsets are associated with ultimate disease diagnosis and response to treatment.

Design/Methods: This study has been approved by the University of British Columbia Research Ethics Board. We are performing a retrospective chart review of patients who had extended T cell phenotyping at BC Children’s Hospital flow cytometry lab from January 1, 2020 to September 30, 2023. Specifically, we are analyzing the proportions of naïve, central memory, effector memory, CD45RA+ effector memory, CD57+ and PD1+ T cell populations in both CD4 and CD8 T cells. Patients will be classified into the following diagnostic categories: i) healthy immune system; ii) primary T cell disorder; and iii) secondary T cell disorder. Kruskal-Wallis one-way ANOVA and Tukey post hoc test will be used to explore the association of specific T cell subpopulations and clinical phenotype. A combination of decision tree and classification models (elastic net, SVM, LDA, etc) will be used to determine whether abnormalities in specific T cell subsets can predict the patient’s diagnosis (primary vs secondary T cell disorder). We will then perform Wilcoxon test to determine the association between T cell subset perturbation and treatment response. Anticipated study completion date: March 31, 2024.