No Immune Risk Profile among individuals who reach 100 years of age: findings from the Swedish NONA immune longitudinal study.

In the present NONA immune longitudinal study, we investigate the previously identified Immune Risk Profile (IRP), defined by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and increased numbers of CD8+CD28- cells, relative 6-year survival and age in NONA individuals. These subjects have now reached age 92, 96, and for the first time in this study, 100 years at follow-up. A 55 year old middle-aged group was used for comparison. Immunological monitoring included the analysis of numbers of lymphocytes and neutrophils, the T-cell subsets CD3+CD4+, CD3+CD8+, CD8+CD28+, CD8+CD28-, and the CD4/CD8 ratio. Longitudinal data were analysed by multivariate analyses of variance (MANOVA) from four measurement occasions at 2-year inter-intervals. One-way ANOVA was used for cross-sectional comparisons at baseline and the 6-year follow-up. The results confirmed the importance of the IRP as a major predictor of mortality in this population of very old. Moreover, the results suggested that survival to the age of 100 years is associated with selection of individuals with an "inverted" IRP that was stable across time, i.e., maintenance of a high CD4/CD8 ratio and low numbers of CD8+CD28- cells. The results underlines the importance of a longitudinal study design in dissecting immune parameters predictive of survival and show for the first time that centenarian status is associated with avoidance of the IRP over at least the previous 6 years and probably throughout life.