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Immune cell infiltration-related clinical diagnostic model for Ankylosing Spondylitis
Chenxing Zhou1, Tuo Liang1, Jie Jiang1
1Department of Spine and Osteopathy Ward, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Abstract:
Background: The pathogenesis and diagnosis of Ankylosing Spondylitis (AS) has remained uncertain due to several reasons, including the lack of studies on the local and systemic immune response in AS. To construct a clinical diagnostic model, this study identified the micro RNA-messenger RNA (miRNA-mRNA) interaction network and immune cell infiltration-related hub genes associated with AS. Materials and Methods: Total RNA was extracted and purified from the interspinous ligament tissue samples of three patients with AS and three patients without AS; miRNA and mRNA microarrays were constructed using the extracted RNA. Bioinformatic tools were used to construct an miRNA-mRNA network, identify hub genes, and analyze immune infiltration associated with AS. Next, we collected the blood samples and clinical characteristics of 359 patients (197 with AS and 162 without AS). On the basis of the clinical characteristics and results of the routine blood tests, we selected immune-related cells whose numbers were significantly different in patients with AS and patients without AS. Univariate and multivariate logistic regression analysis was performed to construct a nomogram. Immunohistochemistry staining analysis was utilized to verify the differentially expression of LYN in AS and controls. Results: A total of 225 differentially expressed miRNAs (DE miRNAs) and 406 differentially expressed mRNAs (DE mRNAs) were identified from the microarray. We selected 15 DE miRNAs and 38 DE mRNAs to construct a miRNA-mRNA network. The expression of LYN, an immune-related gene, correlated with the counts of monocytes, neutrophils, and dendritic cells. Based on the independent predictive factors of sex, age, and counts of monocytes, neutrophils, and white blood cells, a nomogram was established. Receiver operating characteristic (ROC) analysis was performed to evaluate the nomogram, with a C-index of 0.835 and AUC of 0.855. Conclusion: LYN, an immune-related hub gene, correlated with immune cell infiltration in patients with AS. In addition, the counts of monocytes and neutrophils were the independent diagnostic factors for AS. If verified in future studies, a diagnostic model based on these findings may be used to predict AS effectively.
Insights
This study identifies immune cell counts, specifically monocytes and neutrophils, as key diagnostic factors for Ankylosing Spondylitis (AS). These findings could lead to a new diagnostic model for AS.
Area of Science:
- Immunology
- Genetics
- Bioinformatics
Background:
- The pathogenesis and diagnosis of Ankylosing Spondylitis (AS) remain unclear due to limited research on local and systemic immune responses.
- Identifying key molecular interactions and immune cell involvement is crucial for developing diagnostic models for AS.
Purpose of the Study:
- To construct a clinical diagnostic model for Ankylosing Spondylitis (AS) by identifying microRNA-messenger RNA (miRNA-mRNA) interaction networks.
- To pinpoint immune cell infiltration-related hub genes associated with AS.
- To analyze the diagnostic potential of immune cell counts and specific genes in AS.
Main Methods:
- MicroRNA and mRNA microarrays were used to analyze interspinous ligament tissue from AS patients and controls.
- Bioinformatic tools constructed miRNA-mRNA networks and identified hub genes.
- Logistic regression and nomogram analysis were performed on clinical data from 359 patients to identify diagnostic factors, including immune cell counts (monocytes, neutrophils, white blood cells) and gene expression (LYN).
Main Results:
- A total of 225 differentially expressed miRNAs and 406 differentially expressed mRNAs were identified.
- The immune-related gene LYN expression correlated with monocyte, neutrophil, and dendritic cell counts.
- A nomogram incorporating sex, age, and immune cell counts (monocytes, neutrophils, white blood cells) demonstrated high diagnostic accuracy (C-index: 0.835, AUC: 0.855).
Conclusions:
- LYN, an immune-related hub gene, is associated with immune cell infiltration in Ankylosing Spondylitis (AS).
- Counts of monocytes and neutrophils are identified as independent diagnostic factors for AS.
- A diagnostic model based on these immune markers holds potential for effective AS prediction.
