253-OR: Circulating Neutrophil Numbers Increase with Age, but Are Not a Biomarker of T1D Risk

Abstract

Investigations into the role of the neutrophil in type 1 diabetes (T1D) have provided controversial results. It is thus essential to understand how neutrophils change with age and if these numbers are linked by T1D. To do this, we utilized whole blood count data from our database, which includes 2619 unique individuals, pancreata slices from nPOD donors, and data points from the Neulasta in T1D clinical trial, NCT00662519. We first examined changes in neutrophils, total white blood cells (WBC), and lymphocytes in individuals with T1D, T2D, controls, and first and second-degree relatives. One way ANOVA showed no significant differences in neutrophils or other WBCs between groups (p>0.05). To account for age-specific effects, we built a quantile regression model using only the control subjects. With this model, a significant age association for neutrophil count was detected and repeated in each clinical group, indicating that age-matching is essential. Comparisons across groups showed that age-normalized neutrophil counts were no different between individuals with T1D, at-risk for T1D, and controls (p>0.05, Mann-Whitney test). We also enumerated neutrophil numbers within the endocrine and exocrine regions of the pancreas. We assessed pancreata from 51 organ donors with and without T1D: there were no observed differences between the groups (p>0.05, one-way ANOVA). Finally, data from the Neulasta trial demonstrated an increase in neutrophil numbers, but no change in the rate of C-peptide loss. We interrogated granulocytic, T cell, and dendritic cell profiles post-Neulasta to determine if changes in these subsets were reflective of treatment effects. While there was an increase in neutrophils immediately after Neulasta, changes did not persist outside of the treatment window. Other blood cell types were not responsive to Neulasta. Together, these data show that neutrophil numbers increase with age and when age correction is applied, the neutrophil is not a reliable biomarker of T1D. Disclosure A. Lin: None. D.J. Perry: None. D. Schatz: None. T.M. Brusko: Board Member; Self; OneVax, LLC. Consultant; Self; Caladrius Biosciences, Inc., Sanofi-Aventis. Speaker’s Bureau; Self; CSL Behring. M.A. Atkinson: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. C.E. Mathews: None.