Introduction
The ability of immune cells to differentiate between healthy cells and abnormal or non-self entities is critical for efficient elimination of potentially harmful pathogens and cells. However, maintaining self-tolerance while preserving defensive immune responses is a complex process that can be disrupted in certain individuals. This can lead to chronic infections or cancers in immunocompromised individuals or autoimmune diseases in those who fail to maintain immunological tolerance to self-antigens. Over 100 chronic inflammatory or autoimmune diseases have been cataloged, affecting 5-10% of the general population[1]. Ankylosing spondylitis (AS) is the most common arthritic condition affecting the spine, characterized by bone spur formation, back pain, spinal fusion, and disability[2]. AS is driven by disseminated inflammation throughout the skeletal system, which leads to new bone formation that underlies the pathological outcomes observed in AS patients[3].
RNA species play diverse roles in cells, and non-coding RNAs (ncRNAs) with distinct functions have been identified, including circular RNAs (circRNAs)[4, 5]. Although generally classified as ncRNAs, certain circRNAs have been shown to yield polypeptides[6, 7]. CircRNAs often harbor miRNA response elements (MREs) and can function as competing endogenous RNAs (ceRNAs) to suppress miRNA functionality[8, 9]. CircRNAs are crucial regulators of gene expression and have been implicated in a range of pathological processes[10], including cancer, autoimmunity, and diseases of the nervous and cardiovascular systems[11-13]. Autoimmune conditions such as systemic lupus erythematosus (SLE)[14, 15], multiple sclerosis (MS) [16], rheumatoid arthritis (RA)[17, 18], primary biliary cholangitis (PBC)[19], and osteoarthritis (OA)[20, 21] have been shown to be regulated by circRNAs. Thus, to study their specific roles in the context of AS has the potential to yield important insights into the disease’s underlying mechanisms and possible therapeutic targets.
The aim of this study was to identify circRNAs that act as ceRNAs (ceRNAs) and play critical functional roles in AS. High-throughput RNA-sequencing (RNA-seq) analyses of peripheral blood mononuclear cells (PBMCs) from AS patients and healthy controls were used to identify differentially expressed circRNAs (DECs) associated with AS. Together, these findings will provide novel insights into the role of circRNAs in the regulation of AS.