Dermatomyositis (DM) and rheumatoid arthritis (RA) are chronic autoimmune diseases with some shared symptoms and complications, including interstitial lung disease. New evidence suggests the immunologic mechanisms of the two conditions may also overlap.
In a study published in PLOS One, Fo Yang, of Nanchang Hongdu Hospital of Traditional Chinese Medicine in Nanchang, China, and colleagues examined molecular similarities between the two diseases using gene expression data from the Gene Expression Omnibus (GEO) repository, a public database. They looked at patterns of gene expression, immune cell activity, and specific biomarkers
The researchers studied three RA synovial tissue datasets and one DM skeletal muscle dataset. Each dataset included data from patients and healthy control participants. Data were confirmed as reliable by testing against two separate patient groups not used in the original analysis. On correcting for any variabilities, they identified 780 differentially expressed genes associated with RA and 739 associated with DM. They went on to discover 47 genes that overlapped in the two conditions by combining two analytical methods. One method was used to identify abnormal genes, and the other grouped genes based on similarities in their activity.
Further analysis of the 47 overlapping genes showed that they had a role in coordinating interleukin-17 signalling, Toll-like receptor activation, and chemokine-mediated immune cell recruitment. These immune responses are known to drive chronic autoimmune inflammation. Their shared appearance in both RA and DM suggests both conditions may have overlapping immune processes evidenced by increased proliferation in activated CD4-positive memory T cells and M2 macrophages in both affected tissues.
LASSO regression and random forest modelling further revealed four high-priority genes: JUNB, NRGN, HCP5, and RARRES3. Two of these, HCP5 and RARRES3, proved quite useful in distinguishing patients from control participants. Both genes were upregulated in RA and DM. They had good diagnostic value, and their expression was associated with infiltration and localization of inflammatory cells. Their effect was most pronounced in natural killer cells, monocytes, T and B cells. HCP5 worked against immune suppression, whereas RARRES3 stopped pro-inflammatory signalling associated with joint destruction and immune cell survival. Core genes were linked with M1/M2 polarization and T-cell subpopulations (P<0.05). Single-cell analysis localized core gene expression to monocytes, natural killer cells, and T and B cells and highlighted inflammatory ligand-receptor interactions.
The findings identify possible biomarkers and immune pathways that could be tested in future studies. They also provide a basis for pathway-guided research exploring the biological links and potential comorbidity between RA and DM.
