IP: Dr. Alberto Orfao de Matos

Resumen del proyecto: Age is associated with a progressive deterioration in the ability of the immune system to effectively respond to (new) antigens, together with the emergence -after the age of 40y- of progressively larger clones of lymphoid and myeloid hematopoietic cells, affecting >20% of adults aged >50-60 years. The general aim of this project is focused on exploring the impact of the presence of small lymphoid- and/or myeloid-cell clones on the age-related decline (senescence) of immune system, which preferentially affect the humoral response. For this general objective, we propose: 1) To identify -within the general adult population >40 years from Castilla y León-, subjects carrying i) small clones of B cells (MBL-like), T cells (T-CUS), plasma cells (MGUS) and/or ii) the antibody produced by these latter cells; 2) To screen for the presence of genetic mutations associated to (typically age-related) clonal hematopoiesis (CH), that mainly affect myeloid cells; 3) To analyze the distribution in blood of the different cell subsets of normal B and plasma cells according to their maturation stages, and 4) serum levels of different isotypes of antibodies, including specific IgG antibodies against CMV, EBV and SARS-CoV-2; 5) To analyze the BCR repertoire of purified pre-germinal center and memory B cells from blood; 6) To determine the replicative history of the different maturational B-cell compartments; and 7) To quantify plasma levels of (a subset of) 4 sex hormones. In the last phase of the project, we will design a test that would allow the prospective evaluation of the ability of each subject to adequately respond to antigenic stimuli -in a precise and personalized way-.

Entidad financiadora: Instituto de Salud Carlos III