Diabetes and other autoimmune endocrine diseases
OBJECTIVES: The goal of this project is to provide a detailed description of immune subsets from a cohort of T1D affected and unaffected donors and to assess the impact of age and disease status on circulating immunophenotypes. We hypothesize that establishing normal immunophenotypic baselines will facilitate biomarker identification.
METHODS: Blood donations were collected from a cohort of controls (n=164, age=26.7±11.2), relatives (n=342, age=31.8±16.0), and T1D patients (n=204, age=21.1±12.3). Whole blood was surface stained with six fluorescent antibody panels and complete blood counts (CBC) were measured, allowing for detailed adaptive and innate immune subset classification. In total, 351 percentage, mfi, CBC, and absolute count parameters were collected. Elastic net logistic regression analyses were used to predict the age and clinical statuses of donors using these immunophenotypes as covariates.
RESULTS: Circulating populations of immune cells were highly dynamic under age 30 and generally stable after age 40. In addition to the expansion of memory and contraction of naïve T cell populations, we also observed dramatic shifts in naïve CD4+CXCR3+, naive CD4+CXCR5lo, CD8+CXCR5lo Tem, and CD4+PD1+ Tcm subsets. Moreover, we were able to accurately predict donor age based on immunophenotypic parameters (predicted vs actual age Pearson r=0.997 for controls, r=0.978 for relatives, r=0.938 for T1D). Finally, several phenotypic differences were found in patients compared to age-matched controls, including increased naïve CD8+CXCR3+ (p+CD185+ (p< 0.01), and decreased CD8+CD279+ Tcm (p < 0.01). Herein, we have constructed a comprehensive description of the immune repertoire and have identified several putative T1D biomarkers.
University of Florida