Correlation between clinical assessment of frailty (FI) and T cell parameters associated with immunosenescence

Serious Outcomes Surveillance (SOS) Network, Serious Outcomes Surveillance (SOS) Network and Serious Outcomes Surveillance (SOS) Network

The elderly are at increased risk of influenza infection and of severe disease and do not respond to influenza vaccination as well as younger adults. Immunosenescence likely plays an important role in determining the susceptibility of elderly individuals to influenza infection and may predict more severe disease. A number of age-related changes have been observed which are considered indicators of poor immunological function. Although all components of the immune system appear affected by aging, changes in T-cell parameters are by far the most pronounced. Immune biomarkers related to immunosenescence have been successfully validated as predictors of mortality in a Swedish cohort. Immunosenescence has been proposed as a potential cause of frailty and of “aging,” and has important implications for health. What is less well known is how frailty relates to immunosenescence.

We propose to explore the relationship between FI and T cell parameters related to immunosenescence. Frailty will be assessed in all enrolled cases and controls ≥65y as previously described. Peripheral blood mononuclear cells (PBMCs) will be collected at the time of enrollment and at 30d post-discharge from all consenting cases and controls ≥65y enrolled at SOS sites capable of processing PBMCs. A pilot study was conducted in year 1 to assess the feasibility of PBMC collection across the SOS and demonstrated feasibility in 3 of 8 participating sites (Hamilton, Halifax, and Vancouver). The capability of additional SOS sites to process PBMCs is being evaluated. We aim to collect PBMCs from 200 participants (cases or controls) at enrollment and at day 30. Based on enrollment in Year 1/2, this should be feasible even if only the identified 3 SOS sites can participate.

PBMCs will be processed, frozen and shipped using existing standard operating procedures to the Human Immune Testing Suite (HITs) at McMaster University, directed by Dr. Jonathan Bramson. Frozen PBMC’s will be analyzed using multi-parametric flow cytometry to characterize the immunological phenotypes of the circulating immune parameters in each patient. We will survey the distribution of known effector T-cell subtypes based on the expression of CD3, CD8, CD4, CD28, CD57, CD25, CD127 and FOXP3 which allow simultaneous assessment of distributions of CD4+ T-cells, CD4+CD28-T-cells, CD8+ T-cells, CD8+CD28- T-cells and Tregs (all of these parameters have been associated with immunosenescence). T cell parameters will be correlated with clinical assessments of frailty.