Causal relationship between the immune cells and ankylosing spondylitis: univariable, bidirectional, and multivariable Mendelian randomization.

Background: Ankylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored. Methods: We chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran's Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells. Results: Overall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E-05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E-05, OR: 2.9871, 95%CI: 1.8289-4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E-06, OR: 0.5446, 95%CI: 0.4260-0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E-06, OR: 0.0.5423, 95%CI: 0.4210-0.6983). Our findings were consistently stable and reliable. Conclusions: Our findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration.

Posterior Lateral Endoscopic Cervical Discectomy Through a Lateral Mass Approach in the Treatment of Cervical Spondylotic Radiculopathy.

OBJECTIVE: The present study outlines the feasibility, safety, and short-term clinical outcomes of posterior lateral endoscopic cervical discectomy (PLECD) through a lateral mass approach for treating cervical spondylotic radiculopathy (CSR). METHODS: This single-center retrospective observational study involved 30 patients with single-level CSR who had failed conservative treatment and presented with clinical symptoms consistent with imaging findings undergoing PLECD via a lateral mass approach. Primary outcomes included the visual analog scale (VAS) for neck and arm pain, the Japanese Orthopedic Association (JOA) score, and the modified MacNab criteria. Radiographic follow-up consisted of static and dynamic cervical radiographs and computed tomographic scans. RESULTS: Thirty patients (13 men and 17 women; mean age 48.8 ± 11.9 years) underwent this procedure, and the mean operative time was 74.90 ± 13.52 minutes. Mean follow-up was 7.37 ± 2.17 months. The VAS scores for the neck and arm decreased significantly at the last follow-up (neck, 26.80 ± 4.75 to 9.87 ± 1.78; arm, 71.30 ± 8.48 to 14.73 ± 4.00) (P < 0.05). The JOA score also decreased from 13.47 ± 1.36 to 15.90 ± 0.92 at the last follow-up (P < 0.05). Twenty-nine patients demonstrated satisfactory outcomes based on the modified MacNab criteria at the last follow-up. All patients exhibited a positive clinical response, experiencing relief from symptoms. Postoperative computed tomography (CT) scans confirmed the complete removal of lesions. CONCLUSIONS: PLECD through a lateral mass approach, as an alternative to conventional "keyhole" approaches, proves to be a novel and viable therapeutic option for CSR, demonstrating both high efficacy and safety.

Causal relationship between the blood immune cells and intervertebral disc degeneration: univariable, bidirectional and multivariable Mendelian randomization.

Background: Intervertebral disc degeneration (IVDD) is a prominent contributor to chronic low back pain, impacting millions of individuals annually. Current research on disc degeneration is placing a growing emphasis on the role of the immune system in this process. Nevertheless, the precise relationship between immunity and disc degeneration remains to be fully elucidated. Method: We obtained GWAS data for immune cells from the latest summary-level GWAS, including 6,620 individuals from Sardinian and 746,667 individuals from five global populations. Summary results for IVDD were sourced from the FinnGen consortium, comprising 20,001 cases and 164,682 controls. We conducted a comprehensive univariable Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and IVDD. Primary estimation was carried out using Inverse-Variance Weighting (IVW). To ensure robustness, we employed additional MR methods such as MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Various tests were employed to assess pleiotropy and heterogeneity, including the Cochran Q test, leave-one-out test, MR-Egger intercept analysis and MR-PRESSO test. To account for potential confounding factors among the immune cells, we conducted a multivariable MR analysis. Finally, we investigated the possibility of a reverse association between immune cells and IVDD through bidirectional MR. Result: In total, our study identified 15 immune cells significantly associated with IVDD through univariable MR. Among these, 9 immune cell types were indicated as potential contributors to IVDD, while 6 were found to have protective effects. Importantly, we observed no evidence of heterogeneity or pleiotropy, signifying the robustness of our results. To mitigate confounding among immune cells, we utilized multivariable MR, leading to the discovery that only 9 immune cell types exerted independent effects on IVDD. These encompassed 7 as risk factors and 2 as protective factors. Additionally, our analysis revealed a bidirectional causal relationship between CD39+ CD4+ T cell %CD4+ T cell and IVDD. Conclusion: Our findings suggest a connection between immune cells and the risk of IVDD, shedding light on potential therapeutic avenues for modulating immune cell function in individuals with IVDD. However, the specific underlying mechanisms warrant further investigation in future experiments.