Mega-Analysis of gene expression profiling data among IMIDs to better understand the mechanism underlying their development

Immune‐mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to chronic inflammation. In the past two decades the use of common biological drugs improved the quality of life of the patients and led to a new paradigm of common molecular based classification for IMIDs.

To explore this paradigm, we searched the public databases for RNA expression datasets to reanalyze and examine DEGs among different IMIDs.

Eligible 28 studies were included in the analysis composed of 6 IMIDs (Psoriasis, Atopic dermatitis, Ulcerative colitis, Crohn’s disease, Rheumatoid arthritis and Osteoarthritis) which included 1645 tissue samples from inflamed and uninflamed sites along with healthy control samples.

We recognized activation of the common innate immune pathways: Pathogen Induced Cytokine Storm Signaling Pathway, IL-17 Signaling, Phagosome Formation, Dendritic Cell Maturation that induce pro inflammatory immune response. Among top activated upstream regulators were TNF, IL1B, IFNG and IL6 which mediate the inflammatory response and that biologic drugs have been designed to inhibit their action.

Machine learning analysis revealed 9 genes that accurately separate the inflamed samples from healthy controls (accuracy=0.96). The majority of the genes have a pro-inflammatory function. The most efficiently separating gene was TMEM165 that mainly express in epithelial cells and play a role in protein glycosylation and proteoglycan synthesis. We hypothesize that altered expression of proteoglycan which play as immunomodulatory regulator of the innate immune response, or impaired glycosylation of epithelial barrier structures that may affect the epithelium permeability, may lead to a chronic inflammatory response.