Identification of lncRNAs associated with the pathogenesis of ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic autoimmune disease affecting the sacroiliac joint. To date, few studies have examined the association between long non-coding RNAs (lncRNAs) and AS pathogenesis. As such, we herein sought to characterize patterns of AS-related lncRNA expression and to evaluate the potential role played by these lncRNAs in this complex autoimmune context.

Overall, our findings highlight several lncRNAs that are specifically expressed in PBMCs of AS patients, indicating that they may play key functions in the pathogenesis of this autoimmune disease. Specifically, we determined that NONHSAT118801.2 and NONHSAT183847.1 may influence the occurrence and development of AS.

We conducted a RNA-seq analysis of peripheral blood mononuclear cell (PBMC) samples isolated from five AS patients and corresponding controls. These data were then leveraged to characterize AS-related lncRNA expression patterns. We further conducted GO and KEGG enrichment analyses of the parental genes encoding these lncRNAs, and we confirmed the validity of our RNA-seq data by assessing the expression of six lncRNAs via qRT-PCR in 15 AS and control patient samples. Pearson correlation analyses were additionally employed to examine the associations between the expression levels of these six lncRNAs and patient clinical index values.

We detected 56,575 total lncRNAs in AS and control patient samples during our initial RNA-seq analysis, of which 200 and 70 were found to be up- and down-regulated (FC > 2 or < 0.05; P < 0.05), respectively, in AS samples relative to controls. In qRT-PCR validation assays, we confirmed the significant upregulation of NONHSAT118801.2, ENST00000444046, and NONHSAT183847.1 and the significant downregulation of NONHSAT205110.1, NONHSAT105444.2, and NONHSAT051856.2 in AS patient samples. We further found the expression of NONHSAT118801.2 and NONHSAT183847.1 to be positively correlated with disease severity.