Multivariate analysis of immunosenescence data in healthy humans and diverse diseases

Ana Laura Añé-Kourí ^1,2* Jorge Luis Palomino ¹ Patricia Lorenzo-Luaces ¹ Lizet Sanchez ¹ Nuris Ledon ¹ Karla Pereira ¹ Jenysbel de la Caridad Hernández ¹ Gisela María Suarez ³ Beatriz García ¹ Amnely Gonzalez ¹ Danay Saavedra ^1,4* Lage Agustin ¹

• ¹ Center of Molecular Immunology (Cuba), Havana, La Habana, Cuba
• ² Biomedical Research Institute, Faculty of Medicine and Life Sciences, University of Hasselt, Hasselt, Limburg, Belgium
• ³ Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi, United Arab Emirates
• ⁴ Diabetes Research Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States

Immunosenescence is a dynamic process, where both genetic and environmental factors account for the substantial inter-individual variability. This paper integrates all the data on immunosenescence markers generated in our laboratory and describes the differences and/or similarities between individuals based on their biological conditions (immunosenescence markers) and their associations with chronological age and health status.The dataset consisted of immunological data from healthy donors, centenarians, patients diagnosed with chronic kidney disease, COVID-19 and non-small cell lung cancer (NSCLC), treatment-naïve or treated with platinum-based chemotherapy. To determine whether there are groups of immunologically different individuals despite their age or clinical condition, cluster analysis was performed. Canonical discriminant analysis was performed to determine which variables characterize each cluster.Results: There are differences in the expression of immunosenescence markers between healthy subjects and patients diagnosed with different pathological conditions, regardless of their age. Meanwhile, the distribution of the clusters indicates the presence of two separate groups of healthy participants, one of them characterized by a high frequency of naïve lymphocytes, and the other with high expression of terminally differentiated lymphocyte subsets. Advanced NSCLC treatment-naïve patients were in the same cluster as a group of healthy subjects. Additionally, centenarians belong to different cluster than healthy subjects, suggesting they might have a unique immune signature.The distribution of clusters appears to be more appropriate than univariate associations of single markers with health and disease. The present work reveals which immune markers are relevant in different physiological and pathological contexts and indicates the need for deeper studies on the biological age of the immune system.