Analysis of soluble mediators of promotion and suppression of the immune response in patients with the 22q11.2 deletion syndrome

Abstract

22q11.2 deletion syndrome (22q11.2DS) is the most common human microdeletion syndrome, with an estimated prevalence of 1:4000 live births. It has a wide phenotypic variability, with more than 180 different related manifestations. Among the clinical findings, immune abnormalities are present in approximately 75% of the cases and includes recurrent infections, atopy and/or autoimmune diseases, suggesting that it is a disease of dysregulation of the immune system. OBJECTIVE: to evaluate soluble mediators of promotion and suppression of the immune response in 22q11.2DS patients. Fifteen patients with a confirmed diagnosis of 22q11.2DS and 15 healthy patients without a family history of 22q11.2DS, major congenital malformations or a clinical history suggestive of immunodeficiencies were enrolled in the study. Through the sample of peripheral blood, analyzes of mediators related to immune regulation were performed, using techniques of Cytometric Bead Array (CBA) and enzyme-linked immunosorbent assay (ELISA). The study comprised a total of 15 22q11.2DS patients (15.5 years ± 8.4; 4 women and 11 men) and 15 healthy individuals (17.5 years ± 7.2; 7 men and 8 women). When comparing 22q11.2DS patients with healthy individuals, the patients presented higher levels of TREM1, MCP1, IL8 and reduced levels of sOX40 and RANTES. When comparing 22q11.2DS patients with and without autoimmune disease, the group with autoimmune disease has increased levels of sTREM1, s4-1BB, IP10, RANTES, sPD1 and reduced levels of sOX40 and sPDL1. 22q11.2DS patients have defects in the production of soluble mediators involved in the promotion and suppression of the inflammatory response, being essential to maintain the physiological balance of the immune system, regardless of exposure to external factors that may trigger the activation of the immune response. The mediators evaluated can be used as biomarkers to predict autoimmunity in patients with 22q11.2DS.