Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies

Abstract

BackgroundRheumatoid arthritis (RA) refers to an autoimmune rheumatic disease that imposes a huge burden on patients and society. Early RA diagnosis is critical to preventing disease progression and selecting optimal therapeutic strategies more effectively. In the present study, the aim was at examining RA’s diagnostic signatures and the effect of immune cell infiltration in this pathology.MethodsGene Expression Omnibus (GEO) database provided three datasets of gene expressions. Firstly, this study adopted R software for identifying differentially expressed genes (DEGs) and conducting functional correlation analyses. Subsequently, we integrated bioinformatic analysis and machine-learning strategies for screening and determining RA’s diagnostic signatures and further verify by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. Moreover, this study employed cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) website for assessing the inflammatory state of RA, and an investigation was conducted on the relationship of diagnostic signatures and infiltrating immune cells.ResultsOn the whole, 54 robust DEGs received the recognition. Lymphocyte-specific protein 1 (LSP1), Granulysin (GNLY), and Mesenchymal homobox 2 (MEOX2) (AUC = 0.955) were regarded as RA’s diagnostic markers and showed their statistically significant difference by qRT-PCR. As indicated from the immune cell infiltration analysis, resting NK cells, neutrophils, activated NK cells, T cells CD8, memory B cells, and M0 macrophages may be involved in the development of RA. Additionally, all diagnostic signatures might be different degrees of correlation with immune cells.ConclusionsIn conclusion, LSP1, GNLY, and MEOX2 are likely to be available in terms of diagnosing and treating RA, and the infiltration of immune cells mentioned above may critically impact RA development and occurrence.

Single-Cell Transcriptomics Reveals Peripheral Immune Responses in Anti-Synthetase Syndrome-Associated Interstitial Lung Disease

“…We only found significant differences in the ratio CD8 TEM GNLY to CD8 Naïve between patients with ASS-ILD and HDs. Current researches have reported the correlations between GNLY or CD8 T cells and several autoimmune diseases, such as differential expressions of GNLY in rheumatic arthritis and healthy state, an association of GNLY expressions in CD8 cells and steroid resistance in polymyositis, an association of disease flares and proportions of activated CD8 T cells in systemic lupus erythematosus (32)(33)(34). Our study showed that CD8 T cells in the blood of patients with ASS-ILD were skewed towards an activated phenotype characterized by high expression of GNLY.…”

[Retracted] Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis

“…The synovial tissue is of interest for gene analysis in RA. In several previous studies on RA, bioinformatic analyses have been performed with the following research objectives: identifying key genes for diagnosis [ 26 – 33 ], immune infiltration [ 28 , 31 – 33 ], and therapeutic targets [ 26 , 32 ]; however, the sample size of these studies was not very large, and the research content that integrates these three research objectives is lacking. Therefore, various bioinformatic tools were used in this study to analyse differentially expressed gene (DEG) data between patients with RA and healthy individuals from the comprehensive gene expression database [ 34 – 38 ].…”

Identification of hub genes for adult patients with sepsis via RNA sequencing

“…GNLY is a cytotoxic granular protein secreted by cytotoxic T lymphocytes and NK cells 45 that exerts toxic effect on bacteria, fungi, parasites, and tumors 46 , GNLY acts as an immune alarmin and promotes antigen-presenting cell activation through TLR4 47 . GNLY is associated with the efficacy of pegylated-interferon-alpha therapy in Chinese patients with HBeAg-positive chronic hepatitis 48 , rheumatoid arthritis 49 , and Mycoplasma pneumoniae pneumonia 50 . IL2RB, a subunit of IL-2R, mediates signal transduction for IL-2R and IL-15R 51 , Mutations in human IL2RB result in immune dysregulation, cytomegalovirus (CMV) susceptibility 52 , reduced T reg frequency, and an abnormal NK compartment 53 .…”