Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis

Abstract

IntroductionThe specific pathogenesis of ankylosing spondylitis (AS) remains unclear, and our study aimed to investigate the possible pathogenesis of AS.Materials and MethodsTwo datasets were downloaded from the GEO database to perform differentially expressed gene analysis, GO enrichment analysis, KEGG pathway analysis, DO enrichment analysis, GSEA analysis of differentially expressed genes, and construction of diagnostic genes using SVM and WGCNA along with Hypoxia-related genes. Also, drug sensitivity analysis was performed on diagnostic genes. To identify the differentially expressed immune genes in the AS and control groups, we analyzed the composition of immune cells between them. Then, we examined differentially expressed genes in three AS interspinous ligament specimens and three Degenerative lumbar spine specimens using high-throughput sequencing while the immune cells were examined using the neutrophil count data from routine blood tests of 1770 HLA-B27-positive samples and 7939 HLA-B27-negative samples. To assess the relationship between ANXA3 and SORL1 and disease activity, we took the neutrophil counts of the first 50 patients with above-average BASDAI scores and the last 50 patients with below-average BASDAI scores for statistical analysis. We used immunohistochemistry to verify the expression of ANXA3 and SORL1 in AS and in controls.ResultsANXA3 and SORL1 were identified as new diagnostic genes for AS. These two genes showed a significant differential expression between AS and controls, along with showing a significant positive correlation with the neutrophil count. The results of high-throughput sequencing verified that these two gene deletions were indeed differentially expressed in AS versus controls. Data from a total of 9707 routine blood tests showed that the neutrophil count was significantly higher in AS patients than in controls (p < 0.001). Patients with AS with a high BASDAI score had a much higher neutrophil count than those with a low score, and the difference was statistically significant (p < 0.001). The results of immunohistochemistry showed that the expression of ANXA3 and SORL1 in AS was significantly higher than that in the control group.ConclusionUpregulated of ANXA3, SORL1, and neutrophils may be a key factor in the progression of Ankylosing spondylitis.

Identification of three autophagy-related genes as diagnostic biomarkers and analysis of immune cell infiltration in ankylosing spondylitis patients

“…Single-cell RNA sequencing revealed altered NK cells subsets in peripheral circulation of AS patients (34). Increased of neutrophils may be a primary factor in the AS progression (35). These studies revealed that signi cance of immune cell in ltration in the etiopathogenesis of AS.…”

Exploration of the shared pathways and common biomarker PAN3 in ankylosing spondylitis and ulcerative colitis using integrated bioinformatics analysis

“…NETs are the first immune cells to infiltrate the intestinal barrier, and extensive infiltration of NETs is positively correlated with active UC (41). Jiang et al reported that the upregulation of neutrophils may be a key factor in the progression of AS (42). Interestingly, most of the evidence accumulated thus far points to adaptive immunity being related to AS pathogenesis.…”

“…Jiang et al. reported that the upregulation of neutrophils may be a key factor in the progression of AS ( 42 ). Interestingly, most of the evidence accumulated thus far points to adaptive immunity being related to AS pathogenesis.…”

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

“…The fact that there are fewer working neutrophils in the tissues could explain Computational and Mathematical Methods in Medicine why fungi are harder to stop, and the risk of intestinal inflammation is higher [40]. There were also reports that the severity of AS was strongly connected to neutrophils [41,42]. Recently, Zhou et al found that in addition to neutrophils, monocytes were also associated with AS infiltration and identified LYN as a hub gene [43].…”