Expression and Clinical Significance of the m6A RNA-Binding Proteins YTHDF2 in Peripheral Blood Mononuclear Cells From New-Onset Ankylosing Spondylitis

Abstract

This study has focused on determining the association of m6A methyltransferase [methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms tumor 1-associating protein (WTAP)], demethylase [fat mass and obesity-associated protein (FTO) and alkylation repair homolog protein 5 (ALKBH5)], RNA-binding proteins [YT521-B homology domains 2 (YTHDF2)], and ankylosing spondylitis (AS). A total of 154 specimens, containing 79 patients with new-onset AS and 75 healthy controls (HCs), participated in the study. The mRNA expressions of these m6A methyltransferase, demethylase, and RNA-binding protein in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qRT-PCR). The data showed that the mRNA expressions of YTHDF2 and ALKBH5 in PBMC from patients with new-onset AS were significantly decreased, and there was a positive correlation between RNA-binding proteins (YTHDF2) and demethylase (ALKBH5) in patients with new-onset AS. Logistic regression analysis demonstrated that the expression of YTHDF2 mRNA in PBMC is a risk factor of AS. Receiver operating characteristic (ROC) analysis of the area under the curve (AUC) for mRNA YTHDF2 in new-onset AS and HC was 0.692, with a cutoff value of <0.8724, a sensitivity of 67%, and a specificity of 63%. Moreover, we constructed a novel predictive model based on a combination of mRNA YTHDF2 and systemic immune-inflammation index (SII) for AS diagnosis (AUC = 0.865, sensitivity = 79.45%, specificity = 84.00%), and the predictive model correlated with the activity and severity of AS. This study indicates that the mRNA expression of YTHDF2 in PBMC may be involved in AS pathogenesis and a predictive model based on a combination of mRNA YTHDF2 and SII acts as a marker for diagnosis and progression of diseases.

The diagnostic role of the systemic inflammation index in patients with immunological diseases: a systematic review and meta-analysis

“…We identified 16 studies reporting 21 group comparisons which investigated a total of 2893 patients with IDs (mean age 48 years, 42% females) and 2346 healthy controls (mean age 50 years, 44% females) [ 42 – 57 ] (Table 1 ). Six studies were conducted in China [ 44 – 46 , 49 , 52 , 57 ], six in Turkey [ 42 , 43 , 48 , 53 – 55 ], two in South Korea [ 47 , 51 ], one in Egypt [ 50 ], and one in Israel [ 56 ]. Four group comparisons included patients with RA [ 43 , 47 , 50 , 51 ], four with AS [ 44 , 49 , 50 , 56 ], three with UC [ 45 , 46 , 57 ], two with gout [ 52 ], two with SLE [ 50 , 54 ], one with psoriatic arthritis (PsA) [ 48 ], one with OA [ 56 ], one with uveitis [ 42 ], one with sarcoidosis [ 53 ], one with granulomatous polyangiitis (GPA) [ 53 ], and one with IgG4-related disease (IgG4-RD) [ 53 ].…”

“…Six studies were conducted in China [ 44 – 46 , 49 , 52 , 57 ], six in Turkey [ 42 , 43 , 48 , 53 – 55 ], two in South Korea [ 47 , 51 ], one in Egypt [ 50 ], and one in Israel [ 56 ]. Four group comparisons included patients with RA [ 43 , 47 , 50 , 51 ], four with AS [ 44 , 49 , 50 , 56 ], three with UC [ 45 , 46 , 57 ], two with gout [ 52 ], two with SLE [ 50 , 54 ], one with psoriatic arthritis (PsA) [ 48 ], one with OA [ 56 ], one with uveitis [ 42 ], one with sarcoidosis [ 53 ], one with granulomatous polyangiitis (GPA) [ 53 ], and one with IgG4-related disease (IgG4-RD) [ 53 ]. The study design was retrospective in 11 studies [ 42 – 48 , 51 , 52 , 54 , 57 ], and prospective in the remaining five [ 49 , 50 , 53 – 56 ].…”

“…Four group comparisons included patients with RA [ 43 , 47 , 50 , 51 ], four with AS [ 44 , 49 , 50 , 56 ], three with UC [ 45 , 46 , 57 ], two with gout [ 52 ], two with SLE [ 50 , 54 ], one with psoriatic arthritis (PsA) [ 48 ], one with OA [ 56 ], one with uveitis [ 42 ], one with sarcoidosis [ 53 ], one with granulomatous polyangiitis (GPA) [ 53 ], and one with IgG4-related disease (IgG4-RD) [ 53 ]. The study design was retrospective in 11 studies [ 42 – 48 , 51 , 52 , 54 , 57 ], and prospective in the remaining five [ 49 , 50 , 53 – 56 ]. The risk of bias was assessed as low in 13 studies [ 42 , 44 – 47 , 49 – 56 ], and moderate in the remaining three [ 43 , 48 , 57 ] (Table 2 ).…”

Single-cell transcriptome revealed dysregulated RNA-binding protein expression patterns and functions in human ankylosing spondylitis

“…Notably, cell-specific RBPs are involved in regulating the expression of a variety of cell-specific functional proteins, affecting some vital biological processes. For example, the expression of YTHDF2 mRNA in PBMC may be involved in the pathogenesis of AS, and the prediction model based on YTHDF2 can be used as a marker for disease diagnosis and progression ( 16 ). m 6 A modification produced by METTL14 in the 3 ‘UTR region of the ELMO1 gene in AS patients promotes gene expression, while inhibition of ELMO1 expression in mouse models produces therapeutic effects ( 17 ).…”

“…However, relevant studies are still scarce. RNA-binding proteins (RBPs) are key effectors of gene expression ( 13 ), and their abnormal expression is the basis of many diseases ( 14 , 15 ), including AS diseases ( 16–18 ). However, there are few studies on the expression patterns of RBP in different immune cells of AS and the abnormal regulation related to AS disease.…”