Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Abstract

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

Keywords: Down syndrome; autoimmunity; immune dysregulation.

Figure 1

Schematic representation of factors contributing to autoimmunity in patients with Down syndrome. Autoimmunity represents a complex process in which immune dysregulation, genetics, and environmental factors act together. Each factor is capable of influencing and being influenced by the others. Immune dysregulation: Both the innate component (left) and the adaptive component (right) show alterations. Genetic and epigenetic: Genes and miRNAs. Environment: Precocious aging, dietary habits, drugs, microbiota, and chronic inflammation. (IFN: interferon; IFNR: interferon receptor; Ig: immunoglobulin; Treg: T regulatory cell; TRECs: T cell receptor excision circles; AIRE: autoimmune regulator.)