Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis

Abstract

Tuberculosis (TB) is among the leading causes of death by infectious diseases. An epidemiological association between Mycobacterium tuberculosis infection and autoimmune diseases like rheumatoid arthritis (RA) has been reported but it remains unclear if there is a causal relationship, and if so, which molecular pathways and regulatory mechanisms contribute to it. Here we used a computational biology approach by global gene expression meta-analysis to identify candidate genes and pathways that may link TB and RA. Data were collected from public expression databases such as NCBI GEO. Studies were selected that analyzed mRNA-expression in whole blood or blood cell populations in human case control studies at comparable conditions. Six TB and RA datasets (41 active TB patients, 33 RA patients, and 67 healthy controls) were included in the downstream analysis. This approach allowed the identification of deregulated genes that had not been identified in the single analysis of TB or RA patients and that were co-regulated in TB and RA patients compared to healthy subjects. The genes encoding TLR5, TNFSF10/TRAIL, PPP1R16B/TIMAP, SIAH1, PIK3IP1, and IL17RA were among the genes that were most significantly deregulated in TB and RA. Pathway enrichment analysis revealed ‘T cell receptor signaling pathway’, ‘Toll-like receptor signaling pathway,’ and ‘virus defense related pathways’ among the pathways most strongly associated with both diseases. The identification of a common gene signature and pathways substantiates the observation of an epidemiological association of TB and RA and provides clues on the mechanistic basis of this association. Newly identified genes may be a basis for future functional and epidemiological studies.

Integrated Microarray and RNAseq Transcriptomic Analysis of Retinal Pigment Epithelium/Choroid in Age-Related Macular Degeneration

“…Similarly, the RNAseq analysis described by Orozco et al (2020) also highlighted less than 30 putative causal genes for AMD RPE/choroid. Analysis approaches combining different transcriptomic datasets obtained from different platforms were recently used to detect more DE genes in various diseases, such as dilated cardiomyopathy ( Alimadadi et al, 2020 ), Alzheimer’s disease ( Su et al, 2019 ), tuberculosis ( Wang et al, 2018 ), rheumatoid arthritis ( Badr and Häcker, 2019 ), and helminth infection ( Zhou et al, 2016 ). These integrated analyses expand the number of specimens analyzed and are also well suited for AMD, given the multifactorial nature of the disease.…”

Tuberculosis comorbidity with rheumatoid arthritis: Gene signatures, associated biomarkers, and screening

“…As shown in Tables 1 and 2, as well as Figures 1 and 2, genes from both TB infection and RA, are involved in similar pathways, but these two have not yet been evaluated simultaneously in any study. There is only a meta‐analysis study in 2019 by Badr and Häcker using public gene expression data and computational biology investigated the shared gene signatures and pathways between TB infection and RA 35 . They analyzed whole blood mRNA‐expression in 6 independents case–control human studies (41 active TB patients, 33 RA patients, and 67 healthy controls).…”

“…The results showed 172 genes differentially regulated through the gene expression meta‐analysis and the most highly significant shared pathways between TB and RA involved in innate immunity and antiviral defense pathways. Among 172 genes, the genes encoding TNFSF13B/BAFF, TLR5, SIAH1, PPP1R16B/TIMAP, IL17RA, and PIK3IP1 were most significantly deregulated in RA and TB infection 35 …”

“…TLR5 upregulated in both RA and TB infection can contribute to the clinical association of RA and TB infections 35 . It has a significant role in the reaction of DCs and macrophages, activation of pro‐inflammatory signals, and cytokine production in TB infection 39 .…”

“…The role of SIAH1 in TB infection and RA is not clear, and more research is needed. Badr and Häcker also showed many genes such as TRAIL, MLKL (mixed lineage kinase domain‐like), EIF2AK2, and caspase‐1/5 have a significant role in programmed cell death (necroptosis, pyroptosis, or apoptosis) during TB infection and RA and have a correlation with disease activity 35 . Other significant gene signatures, including EIF2AK2, DDX58, OAS1, CASP1, and GSK3B, play a role in viral response‐related pathways 35 …”