Diagnostic value of anti-Kaiso autoantibody in axial spondyloarthritis

ObjectiveAxial spondyloarthritis (axSpA) is a chronic rheumatic disease predominantly characterized by inflammation and progressive structural damage. Patients are often diagnosed very late, which delays the optimal treatment period. Early diagnosis of axSpA, especially non-radiographic axSpA (nr-axSpA), remains a major challenge. This study aimed to investigate the diagnostic value of anti-Kaiso autoantibodies in axSpA and their correlation with clinical disease indicators.MethodsTwo pooled serum samples (seven patients with nr-axSpA and seven healthy controls) were profiled using HuProt arrays to investigate the diagnostic value of autoantibodies in nr-axSpA. Levels of anti-Kaiso autoantibodies in patients with axSpA and controls were determined using the Meso Scale Discovery assay system. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of anti-Kaiso autoantibodies in axSpA. Pearson’s correlation was used to assess the correlation between anti-Kaiso autoantibodies and clinical parameters.ResultsSeven candidate autoantibodies were present in the serum of patients with nr-axSpA. The levels of anti-Kaiso autoantibodies were significantly higher in the nr-axSpA group than in the other groups. It can differentiate nr-axSpA from ankylosing spondylitis (AS), healthy controls, and rheumatoid arthritis. The level of early-stage AS among patients with nr-axSpA decreased when they progressed to the late stage. Of all patients with axSpA, serum anti-Kaiso autoantibody levels were positively correlated with the C-reactive protein level and the Bath Ankylosing Spondylitis Disease Activity Index score and negatively correlated with disease duration.ConclusionAnti-Kaiso autoantibody may be a valuable diagnostic biomarker for early-stage AS in the nr-axSpA period and may be a potential therapeutic target

CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

Abstract Background Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice. Methods The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage. Results The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation. Conclusions The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment

NEDD4 Depletion Inhibits Hepatocellular Carcinoma Growth via Targeting PTEN

Background/Aims: Neural precursor cell-expressed developmentally down-regulated gene 4 (NEDD4) plays an important role in tumor cell growth, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study is to establish NEDD4 as a prognostic biomarker by which the survival of HCC patients can be predicted and to reveal the role of NEDD4 in hepatocellular carcinoma cell growth. Methods: The expression of NEDD4 in 219 HCC specimens was assessed by immunohistochemistry. Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses. The roles of NEDD4 in hepatocellular carcinoma cell proliferation and invasion were determined. Results: The patients with low NEDD4 expression tumors had an average cumulative survival of 64.9 ± 6.5 months during follow-up while the patients with high NEDD4 expression tumors had an average cumulative survival of 20.3 ± 15.8 months. NEDD4 silencing inhibited Huh7 cell proliferation and altered cell cytoskeletal assembly, and NEDD4 depletion furthermore seemed to suppress cell migration and invasion. A possible molecular mechanism for the observed effects might be that NEDD4 silence led to an increase in PTEN (phosphatase and tensin homologue) expression, which in turn resulted in the inactivation of STAT3, AKT, and ERK1/2. Conclusion: Our findings indicate that NEDD4 may participate in the HCC progression and may therefore be a potential target for HCC therapy