Genetics of immune-mediated inflammatory diseases

Abstract

Summary Immune‐mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co‐morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome‐wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody‐mediated autoimmune diseases cluster more closely with each other than autoantibody‐negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.

Systematic classification of shared components of genetic risk for common human diseases

“…Although our results falsify the notion of a single hierarchical ontology of underlying genetically determined pathophysiological processes, nevertheless, they can be used to decompose the well-established genetic covariance between traits, such as for IMDs (6)(7)(8). For example, among 91 ICD-10 codes corresponding to IMDs we observe patterns of overlap in genetic risk consistent with previous findings (6)(7)(8)(9)42) (Fig. 5D).…”

Involvement of the Nervous System in SARS-CoV-2 Infection

“…With the increasing awareness of autoantibody-positive cases, autoimmune encephalitis has received increasing attention (Dubey et al 2018). This autoimmune disease is related to genetic susceptibility, infection, and stressful life events, and is caused by excessive self-response and antigen-driven immune responses (David et al 2018;Karagianni et al 2019;Skopouli and Katsiougiannis 2018). In patients with SARS, autoantibodies against the coronavirus spike protein were found to react with human epithelial cells and endothelial cells, and cause cytotoxicity Yang et al 2005).…”

Genomic opportunities for drug repositioning in systemic seropositive rheumatic diseases

“…Drug repositioning is defined as the identification of new applications for existing drugs that have already passed development phases and were previously indicated to treat other diseases. Thus, this method allows saving time and resources providing new applications to existing drugs with known safety profiles [3]. Traditionally, it has been centered on drug-based and disease-based approaches, focused on drugs and disease features, respectively.…”