Differential expression of genes regulated by the glucocorticoid receptor in patients with pulmonary tuberculosis.

GALLUCCI, GEORGINA; IMHOFF MATILDE; ARIANA DIAZ,; FERNÁNDEZ, ROCÍO D. V.; BONGIOVANNI BETTINA; SANTUCCI NATALIA; BERTOLA DIEGO; GARDEÑEZ WALTER,; BAY MARÍA L; BOTTASSO OSCAR; D'ATTILIO LUCIANO

Tucumán

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2019

Sociedad Argentina de Inmunología SAI

Tuberculosis is the mainly cause of death among infectious diseases. We have previouslyshown that patients with pulmonary tuberculosis (TB) present animmuno-endocrine imbalance characterized by a disease-severity associated increasein plasma levels of proinflammatory cytokines, cortisol and the cortisol/DHEAratio, without changes in the expression of the functional isoform of theglucocorticoid receptor (GRα). We now analyzed the expression of GR-regulated genes(RT-qPCR) mostly involved in the down-modulation of the immune response (AnxA1,FKBP5, GILZ, NFKBIBα and NFKBIBβ), in PBMC of adult TB patients, HIV negative (n=47) and healthycontrols (HCo, n=47).Transcript levels of AnxA1 (p=0.006),GILZ (p=0.033) and NFKBIBβ (p=0.041)mRNA appeared significantly increased in TB patients respect to HCo, whereas theexpression of FKBP5 and NFKBIBα remained unchanged. When analyzing according to diseaseseverity, mRNA for AnxA1 (p=0.006) and NFKBIBβ (p=0.025) were higher in moderate and severe TB ifcompared to Hco; whereas, GILZ and NFKBIBα appeared increased in moderate and severe,respectively. Regarding GR isoforms, GRβ wasincreased in severe TB (), without significant modifications in GRα transcriptlevels. Plasma levels of proinflammatory cytokines (IFN-γ, IL-6) and cortisolwere increased in TB patients (p<0.01 vs. Hco). The differential modulationin the expression of distinct GR-dependent transcripts, particularly inprogressive disease, seemingly related to an unbalanced GRα/GRβ ratio, is compatible with a relativelyinsufficient attempt to downregulate the protracted inflammation accompanying advanceddisease.