Gene Expression Meta-Analysis of Potential Shared and Unique Pathways between Autoimmune Diseases under Anti-TNFα Therapy

Abstract

While anti-TNFα has been established as an effective therapeutic approach for several autoimmune diseases, results from clinical trials have uncovered heterogeneous patients’ response to therapy. Here, we conducted a meta-analysis on the publicly available gene expression cDNA microarray datasets that examine the differential expression observed in response to anti-TNFα therapy with psoriasis (PsO), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Five disease-specific meta-analyses and a single combined random-effects meta-analysis were performed through the restricted maximum likelihood method. Gene Ontology and Reactome Pathways enrichment analyses were conducted, while interactions between differentially expressed genes (DEGs) were determined with the STRING database. Four IBD, three PsO and two RA datasets were identified and included in our analyses through our search criteria. Disease-specific meta-analyses detected distinct pro-inflammatory down-regulated DEGs for each disease, while pathway analyses identified common inflammatory patterns involved in the pathogenesis of each disease. Combined meta-analyses further revealed DEGs that participate in anti-inflammatory pathways, namely IL-10 signaling. Our analyses provide the framework for a transcriptomic approach in response to anti-TNFα therapy in the above diseases. Elucidation of the complex interactions involved in such multifactorial phenotypes could identify key molecular targets implicated in the pathogenesis of IBD, PsO and RA.

Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn’s Colitis among Indeterminate Colitis Cohorts

“…Whole-transcriptome microarray with RNA extracted and pooled from human full thickness colon samples from UC and CC patients (n = 5/group) (Affymetrix, Santa Clara, CA) as previously described. 22 , 23 …”

“…Quantification of DEFA5 staining was analyzed manually by microscopy / automatically quantified using Nikon's Eclipse Ti microscope with built-in NIS-Elements Advanced Research software (NEARAS). 22 , 28 …”

“…Nikon Elements Advanced Research Software (NEARAS) (Melville, NY) was used to manually calculate the number of cells with DEFA5 staining in IHC tissue slides. 22 , 28 A mean intensity threshold of 20 to 255 intensity units was established to eliminate a false positive signal from background staining. A circularity parameter of 0.5 to 1 and equivalent diameter of 5-15 micrometer was used to select for cells.…”