Osteoimmunological insights into the pathogenesis of ankylosing spondylitis

Liu, Lifei; Yuan, Yu; Zhang, Shihua; Xu, Jiake; Zou, Jun

doi:10.1002/jcp.30313

Cited by 45 publications

(30 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(2) CDC42 regulates the differentiation of the osteoclasts and osteoblasts, further maintain the function of bone modeling and remodeling. Thus, the downregulation of CDC42 might be correlated with the initiation of the AS 30‐33 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

Zhang¹,

Du²,

Mou³

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Objective Cell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy. Methods Peripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF‐α, interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), and interleukin‐17A (IL‐17A) from AS patients were detected at baseline. Results Blood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = −0.349, p = 0.001), BASDAI score (r = −0.243, p = 0.020), and ASDASCRP score (r = −0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF‐α (r = −0.237, p = 0.024) and IL‐17A (r = −0.339, p = 0.001) but not with IFN‐γ (p = 0.083) or IL‐10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non‐response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non‐response patients after treatment. Conclusion Blood CDC42 deficiency links with elevated pro‐inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Thus, the downregulation of CDC42 might be correlated with the initiation of the AS. 30 , 31 , 32 , 33 …”

Section: Discussionmentioning

confidence: 99%

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

Zhang¹,

Du²,

Mou³

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…The pathological changes and osteoimmunological features of AS mainly include osteolytic bone destruction and osteogenic changes. The interaction of T cells, B cells, osteoblasts, and osteoclasts together regulate the pathogenesis of AS ( 6 ). More importantly, the long course of AS as a chronic inflammatory disease makes the emotional and financial devastation of the patient unbearable.…”

Section: Introductionmentioning

confidence: 99%

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

Jiang

Zhan

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

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.

show abstract

“…However, the pathogenesis of bone erosion and bone formation in AS is not completely understood 5 . In recent years, many studies have reported that cytokines play a vital role in disease pathology, 6‐9 and other studies have reported that the dysregulation of the immune system and bone metabolism may play a critical role in AS etiology 10,11 …”

Section: Introductionmentioning

confidence: 99%

Leukemia inhibitory factor is dysregulated in ankylosing spondylitis and contributes to bone formation

Kong

Tang

et al. 2022

Int J of Rheum Dis

View full text Add to dashboard Cite

Aim Ankylosing spondylitis (AS) is a chronic inflammatory disease. However, the key inflammatory cytokines disrupted in this disease are not well defined. In this study, we performed protein array and multiple protein quantification to investigate the differentially expressed cytokines in plasma between AS patients and healthy subjects. Method In the discovery cohort, 5 AS patients who never underwent biologic therapy and 5 gender‐ and age‐matched healthy subjects were enrolled in the protein array analysis. Another 40 AS patients and 20 healthy participants were recruited in the validation stage. In addition, the messenger RNA and protein levels of osteogenesis‐related genes were quantified in hFOB1.19 cells in an in vitro osteoblast model. Results Of the 318 cytokines found to be differentially expressed by protein array, leukemia inhibitor factor (LIF) was significantly increased in AS patients as compared to controls. The “signaling by interleukins” pathway was the most enriched pathway in AS patients, and “signaling by interleukins”‐related cytokines, including LIF, interleukin (IL)‐6, IL‐23, and IL‐31, were significantly differentially expressed in the validation stage. Additionally, we correlated the expression of LIF with C‐reactive protein (CRP) and inflammation of magnetic resonance imaging lesions in the spine (MRI‐SPINE) in AS patients. We further analyzed the effects of LIF in hFOB cells and found that LIF promoted the growth factor receptor‐bound protein 2 / phospho‐extracellular signal‐regulated kinase / runt‐related transcription factor 2 / alkaline phosphatase pathway at the protein level and activated several osteogenesis‐related genes (RUNX2 and BGLAP). Conclusion LIF was increased in the plasma of AS patients as compared with healthy subjects and significantly correlated with inflammation indices (CRP and MRI‐SPINE) in AS patients. Thus, LIF may play a critical role in the pathogenesis of AS via promoting osteogenic differentiation.

show abstract

Osteoimmunological insights into the pathogenesis of ankylosing spondylitis

Cited by 45 publications

References 131 publications

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

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

Leukemia inhibitory factor is dysregulated in ankylosing spondylitis and contributes to bone formation

Contact Info

Product

Resources

About