Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes.
Methods: A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation.
Results: Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4.
Conclusion: Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.
Objective: Triple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC.
Methods: We explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools.
Results: The results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy.
Conclusion: LCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.
Background: Psoriasis has a global prevalence of 1-3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs suggest different genetic regulatory mechanisms which may include NLR family pyrin domain containing 3 (NLRP3) polymorphism. Evaluation of the NLRP3 gene polymorphism, the serum level of CRP and TNFα in psoriasis patients and assessment of the NLRP3 (rs10754558) gene polymorphism, CRP and TNFα with disease severity and their role as biomarkers for response to Methotrexate and Adalimumab in psoriasis. The study had a total of 75 patients diagnosed with psoriasis vulgaris, who were compared to a control group of 75 healthy individuals.
Results: There was a highly significant difference in NLRP3 genotypes and alleles distribution between psoriasis patients and controls (P = 0.002,0.004). The heterozygote genotype GC (OR = 3.67,95%CI:1.75-7.68, P = 0.0006), was linked with increased risk of psoriasis. Additionally, The GC genotype was significantly associated with nonresponse to psoriasis therapy (OR = 11.7,95%CI:3.24-42.28, P = 0.0002). Regarding serum CRP and TNFα levels, there was a highly statistically significant difference between psoriasis patients and controls (P < 0.0001), and there was also a highly statistically significant difference between responders and non-responders in psoriasis patients regarding PASI 50 (P < 0.0001).
Conclusions: The NLRP3 (rs10754558) genotypes GC was associated with the severe form of psoriasis and with nonresponse to psoriasis medication. Therefore, NLRP3 (rs10754558) gene polymorphism is an important prognostic biomarker in psoriasis patients. The serum TNFα can be used as a predictor for response to therapy in psoriasis patients. More research for evaluation of role of the NLRP3 gene polymorphism in the genetic risks and treatment outcomes associated with psoriasis is still required.
Background: Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP).
Results: Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02).
Conclusions: These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.
Background: Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these patients. We designed a network meta-analysis (NMA) to evaluate systemic treatment options for NSCLC after failure of ICIs.
Methods: PubMed, Embase, Web of Science and Cochrane Library databases were searched, then literature screening was followed by NMA. We included all Phase II and III randomized controlled trials (RCTs). Progression-free survival (PFS) and overall survival (OS) used hazard ratio (HR) for evaluation. Objective response rate (ORR) and adverse events (AEs) used odds ratio (OR) and relative risk (RR) effect sizes, respectively. R software was applied to compare the Bayesian NMA results.
Results: We finally included 6 studies. 1322 patients received ICI plus Chemotherapy (ICI + Chemo), ICI plus Anti-angiogenic monoclonal antibody (ICI + Antiangio-Ab), ICI plus Tyrosine kinase inhibitor (ICI + TKI), Tyrosine kinase inhibitor plus Chemotherapy (TKI + Chemo), Standard of Care (SOC), Chemotherapy (Chemo). TKI + Chemo is associated with longer PFS, higher ORR (surface under cumulative ranking curve [SUCRA], 99.7%, 88.2%), ICI + TKI achieved the longest OS (SUCRA, 82.7%). ICI + Antiangio-Ab was granted the highest safety rating for adverse events (AEs) of any grade, AEs greater than or equal to grade 3 and AEs of any grade leading to discontinuation of treatment (SUCRA, 95%, 82%, 93%).
Conclusions: For NSCLC after failure of ICIs, TKI + Chemo was associated with longer PFS and higher ORR, while ICI + TKI was associated with the longest OS. In terms of safety, ICI + Antiangio-Ab was the highest.
Background: Previous observational studies have shown a bidirectional association between immune-mediated inflammatory disorders (IMID) and periodontal disease. However, evidence regarding the causal role of IMID and periodontal disease is still lacking. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to uncover the potential genetic causal effects between IMID and periodontal disease.
Methods: Bidirectional two-sample MR analysis was employed. Data for ten IMIDs were sourced from genome-wide association studies (GWAS) conducted by the FinnGen Consortium (range from 1023 to 36321 cases) and UK Biobank (UKB) (range from 150 to 17574 cases). Furthermore, GWAS data for periodontal disease were obtained from the FinnGen Consortium (87497 cases), UKB (458 cases), and Gene Lifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 periodontitis cases). Subsequently, the causal relationships were analyzed by random effects inverse variance weighting, weighted median, and MR-Egger. Sensitivity analyses were performed using the Cochrane Q test, funnel plot, and Mr-Egger intercept test to ensure robustness. Eventually, replication analysis and meta-analysis across different databases were carried out.
Results: Systemic lupus erythematosus (SLE) [IVW: OR = 1.079 (95% CI: 1.032-1.128) and P < 0.001], Sjogren syndrome [IVW: OR = 1.082 (95% CI: 1.012-1.157) and P = 0.022] and hypothyroidism [IVW: OR = 1.52 (95% CI: 1.13-2.04) and P = 0.005] may increase the risk of periodontal disease. In addition, periodontal disease may reduce the risk of SLE [IVW: OR = 0.8079 (95% CI: 0.6764-0.9650) and P = 0.019] and hyperthyroidism [IVW: OR = 5.59*10-9 (95% CI: 1.43*10-15-2.18*10-2) and P = 0.014]. Meta-analysis indicated a causal correlation between SLE and an increased risk of periodontal disease: [OR = 1.08 (95% CI: 1.03-1.13), P = 0.0009]. No significant evidence suggests bilateral causal relationships between other IMIDs and periodontal disease. No significant estimation of heterogeneity or pleiotropy is detected.
Conclusions: Our study has confirmed a genetic causal relationship between IMIDs and periodontal disease, thereby unveiling novel potential mechanisms underlying IMIDs and periodontal disease. This discovery is promising in fostering interdisciplinary collaboration between clinicians and stomatologists to facilitate appropriate and precise screening, prevention, and early treatment of IMIDs and periodontal disease.
Background: Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.
Objectives: This study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.
Materials and methods: A total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.
Results: Significant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.
Conclusions: Increased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.
Background: For the past three years, the pandemic has had a major effect on global public health, mainly on those with underlying medical conditions, such as people living with Multiple Sclerosis. Vaccination among this group is of great importance, and the long-term impacts of vaccination and its safety on the health of these patients will continue to be revealed. Therefore, risks related to vaccination and immune response need to be assessed. The objective here was to characterize the immune response, short-term safety, and the effects of multiple variables on these factors after COVID-19 vaccination (mainly Sinopharm) among people with Multiple Sclerosis. We assessed the short-term safety and humoral SARS-COV-2 anti-RBD IgG response using a data collection form and Immunoassay, respectively.
Results: No severe adverse events or MS relapse was observed. Myalgia/body pain (26.7%), low-grade fever (22.2%), and mild headache (15.6%) were the most common adverse events. The use and type of vaccine influenced the frequency of side effects with a p-value < 0.0001. Regarding immune response, patients on rituximab and fingolimod had a lower antibody titer compared to other medications. With a significant difference, hybrid immunity (p-value: 0.047) and type of DMTs (p-value: 0.017) affected the humoral response.
Conclusion: There is a low incidence of serious adverse effects, MS worsening or relapse after COVID-19 vaccination, and mainly, side effects are similar to that of the general population. It appears that treatment with various disease-modifying therapies does not induce or worsen the post-vaccination side effects, although some, including Rituximab and fingolimod, may affect the immunity induced after vaccination.
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