Abstract
Several previous studies have attempted to investigate the regulatory mechanisms underlying gene expression in ankylosing spondylitis (AS). However, the specific molecular pathways underlying this condition remain unclear. Previous research used next-generation RNA sequencing to identify a series of differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) when compared between patients with AS and healthy controls, thus implying that these DEGs may be related to AS. Furthermore, by screening these DEGS, it may be possible to facilitate clinical diagnosis and optimize treatment strategies. In order to test this hypothesis, we recruited 15 patients with AS and 15 healthy controls. We randomly selected five subjects from each group of patients for RNA sequencing analysis. Sequence reads were generated by an Illumina HiSeq2500 platform and mapped on to the human reference genome using HISAT2. We successfully identified 973 significant DEGs (p < 0.05) in PBMCs. When compared with controls, 644 of these genes were upregulated (with a fold change (FC) > 2) in AS patients and 329 were downregulated (FC < 0.5). Our analysis identified numerous genes related to immune response. Gene Ontology (GO) analysis indicated that these DEGs were significantly related to the positive regulation of epidermal growth factor-activated receptor activity, the positive regulation of the ERBB (erb-b2 receptor tyrosine kinase) signaling pathway, the differentiation of trophoblast giant cells, oxygen transport, immune-related pathways, and inflammation-related pathways. The DEGs were also closely related to the TNF and NF-κB signaling pathways. Six DEGs were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curve analysis indicated that IL6 may represent a useful biomarker for diagnosing AS. The development of new biomarkers may help us to elucidate the specific mechanisms involved in the development and progression of AS.
Highlights
Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory form of arthritis and is characterized by chronic nonspecific inflammation and pathological bone formation, the latter representing a common clinical form of spondyloarthritis (SpA) [1]
973 differentially expressed genes (DEGs) were identified between the AS and control groups, including 644 upregulated DEGs and 329 downregulated DEGs
Our analysis revealed that a number of Gene Ontology (GO) terms were enriched, including positive regulation of acute inflammatory response (p = 3:170e‐03), acute inflammatory response (p = 7:623e‐05), positive regulation of inflammatory response (p = 1:247e‐03), regulation of acute inflammatory response (p = 8:621e‐03), regulation of inflammatory response (p = 1:988e‐05), inflammatory response (p = 3:196e‐09), negative regulation of inflammatory response (p = 3:462e‐02), immune system process (p = 4:903e‐03), T cell differentiation involved in immune response (p = 7:247e‐03), negative regulation of immune system process (p = 7:468e‐03), type 2 immune response (p = 8:962e‐03), regulation of immune system process (p = 9:386e‐03), immune system development (p = 1:139e‐02), response to immobilization stress (p = 1:267e‐02), regulation
Summary
Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory form of arthritis and is characterized by chronic nonspecific inflammation and pathological bone formation, the latter representing a common clinical form of spondyloarthritis (SpA) [1]. The incidence of AS in China is approximately 0.3% and predominantly affects adults (mean age: 25 years; range: 15–35 years) [2]. Chronic inflammation of the spinal joints can lead to severe chronic pain and stiffness, leading to bone stiffness in the spine; this can exert impact on several other systems [3]. Approximately 30% of patients fail to tolerate these drugs or experience differing degrees of adverse reactions [6]. There is an urgent need to identify new biomarkers that may act as diagnostic or prognostic indicators for AS. The discovery of such biomarkers is likely to prove invaluable in the prevention, treatment, and control of this disease
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