Causal role of immune cells in obstructive sleep apnea hypopnea syndrome: Mendelian randomization study.

BACKGROUND: Despite being one of the most prevalent sleep disorders, obstructive sleep apnea hypoventilation syndrome (OSAHS) has limited information on its immunologic foundation. The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies (GWAS) and genotyping techniques using high-density genetic markers (e.g., SNP or CNVs). But this tactic hasn't yet been applied to OSAHS. Using a Mendelian randomization analysis, we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS. AIM: To investigate the immune cells' association with OSAHS via genetic methods, guiding future clinical research. METHODS: A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS. Summary statistics for each immune cell feature were obtained from the GWAS catalog. Information on 731 immune cell properties, such as morphologic parameters, median fluorescence intensity, absolute cellular, and relative cellular, was compiled using publicly available genetic databases. The results' robustness, heterogeneity, and horizontal pleiotropy were confirmed using extensive sensitivity examination. RESULTS: Following false discovery rate (FDR) correction, no statistically significant effect of OSAHS on immunophenotypes was observed. However, two lymphocyte subsets were found to have a significant association with the risk of OSAHS: Basophil %CD33dim HLA DR- CD66b- (OR = 1.03, 95%CI = 1.01-1.03, P < 0.001); CD38 on IgD+ CD24- B cell (OR = 1.04, 95%CI = 1.02-1.04, P = 0.019). CONCLUSION: This study shows a strong link between immune cells and OSAHS through a gene approach, thus offering direction for potential future medical research.

5-HMF attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis mice by inhibiting the MIF-CD74 interaction.

The neuroprotective role of 5-hydroxymethyl-2-furfural (5-HMF) has been demonstrated in a variety of neurological diseases. The aim of this study is to investigate the effect of 5-HMF on multiple sclerosis (MS). IFN-γ-stimulated murine microglia (BV2 cells) are considered a cell model of MS. With 5-HMF treatment, microglial M1/2 polarization and cytokine levels are detected. The interaction of 5-HMF with migration inhibitory factor (MIF) is predicted using online databases. The experimental autoimmune encephalomyelitis (EAE) mouse model is established, followed by a 5-HMF injection. The results show that 5-HMF facilitates IFN-γ-stimulated microglial M2 polarization and attenuates the inflammatory response. According to the network pharmacology and molecular docking results, 5-HMF has a binding site for MIF. Further results show that blocking MIF activity or silencing CD74 enhances microglial M2 polarization, reduces inflammatory activity, and prevents ERK1/2 phosphorylation. 5-HMF inhibits the MIF-CD74 interaction by binding to MIF, thereby inhibiting microglial M1 polarization and enhancing the anti-inflammatory response. 5-HMF ameliorates EAE, inflammation, and demyelination in vivo. In conclusion, our research indicates that 5-HMF promotes microglial M2 polarization by inhibiting the MIF-CD74 interaction, thereby attenuating inflammation and demyelination in EAE mice.

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study.

Background: Generalized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have seen the widespread use of high-density genetic markers such as SNPs or CNVs for genotyping, as well as the advancement of genome-wide association studies (GWAS) technologies, which have facilitated the understanding of immunological mechanisms underlying several major psychiatric disorders. Despite these advancements, the immunological basis of GAD remains poorly understood. In light of this, we aimed to explore the causal relationship between immune cells and the disease through a Mendelian randomization study. Methods: The summary information for GAD (Ncase=4,666, Ncontrol=337,577) was obtained from the FinnGen dataset. Summary statistics for the characterization of 731 immune cells, including morphological parameters (MP=32), median fluorescence intensity (MFI=389), absolute cells (AC=118), and relative cells (RC=192), were derived from the GWAS catalog. The study involved both forward MR analysis, with immune cell traits as the exposure and GAD as the outcome, and reverse MR analysis, with GAD as the exposure and immune cell traits as the outcome. We performed extensive sensitivity analyses to confirm the robustness, heterogeneity, and potential multi-biological effects of the study results. Also, to control for false positive results during multiple hypothesis testing, we adopted a false discovery rate (FDR) to control for statistical bias due to multiple comparisons. Results: After FDR correction, GAD had no statistically significant effect on immunophenotypes. Several phenotypes with unadjusted low P-values are worth mentioning, including decreased PB/PC levels on B cells(ß=-0.289, 95%CI=0.044~0.194, P=0.002), reduced PB/PC AC in GAD patients (ß=-0.270, 95% CI=0.77~0.92, P=0.000), and diminished PB/PC on lymphocytes (ß=-0.315, 95% CI=0.77~0.93, P=0.001). GAD also exerted a causal effect on CD27 on IgD-CD38br (ß=-0.155,95%CI=0.78~0.94,P=0.002), CD20-%B cell (ß= -0.105,95% CI=0.77~0.94, P=0.002), IgD-CD38br%lymphocyte(ß=-0.305, 95%CI=0.79~0.95, P=0.002), FSC-A level on granulocytes (ß=0.200, 95%CI=0.75~0.91, P=8.35×10-5), and CD4RA on TD CD4+(ß=-0.150, 95% CI=0.82~1.02, P=0.099). Furthermore, Two lymphocyte subsets were identified to be significantly associated with GAD risk: CD24+ CD27+ B cell (OR=1.066,95%CI=1.04~1.10,P=1.237×10-5),CD28+CD4+T cell (OR=0.927, 95%CI=0.89~0.96, P=8.085×10-5). Conclusion: The study has shown the close association between immune cells and GAD through genetic methods, thereby offering direction for future clinical research.