BMC Immunology最新文献

Background and objectives: The identification of affordable and easily accessible indicators to predict overall survival is important for tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells, which promote tumor immune escape in the tumor microenvironment (TME). This study aimed to determine whether peripheral blood MDSCs could determine their potential as predictors of survival in tumor patients with immunotherapy.

Methods: Flow cytometry was used to detect peripheral blood monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic myeloid-derived suppressor cells (G-MDSCs) in 126 patients. Multivariate Cox regression analysis was conducted to examine the associations between peripheral blood MDSCs and patient survival. The receiver operating characteristic (ROC) curve determined the optimal cutoff value for peripheral blood MDSCs and grouped the indicators. The relationship between peripheral blood M-MDSCs and the prognosis and treatment outcome of tumor patients was explored.

Results: The proportion of peripheral blood M-MDSCs was associated with the prognosis of patients with tumors, as were tumor metastasis, the red blood cell count, absolute neutrophil count, absolute monocyte count, and BMI. Multivariate Cox regression analysis revealed that M-MDSCs, absolute lymphocyte value, and tumor metastasis were independent risk factors affecting the prognosis of patients with tumors. Detection of peripheral blood M-MDSCs obtained high sensitivity and specificity for tumor diagnosis. Patients with high M-MDSCs percentage demonstrated reduced survival durations and diminished responses to immunotherapy compared to those with low M-MDSCs percentage.

Conclusions: Peripheral blood M-MDSCs may be used to predict overall survival and immunotherapy efficacy outcomes. This study provides a putative predictive biomarker for clinicians to choose from to predict tumor patients' survival and the selection of receiving immunotherapy regimens.

Background: The human leukocyte antigen (HLA)-B27 gene is highly associated with ankylosing spondylitis (AS). However, not everyone who carries the HLA-B27 antigen develops AS, indicating that factors beyond the HLA-B27 gene contribute to the disease's onset. AS is an autoimmune disease in which co-stimulatory systems have been widely explored. Therefore, we aimed to analyze the association between single-nucleotide polymorphisms (SNPs) in co-stimulatory/inhibitory molecules and AS to identify other key factors involved in developing the disease.

Results: This study recruited 32 patients with AS and 32 controls. DNA was extracted from whole blood, and PCR amplification was performed to target the promoter regions of the CTLA4, CD28, and PDCD1 genes. Chi-square and Fisher's exact tests were used under various genetic models to assess differences in genotype and allele distribution between cases and controls. The results showed that rs201801072 of the CD28 gene (TT + CT vs. CC, p = 0.001) and rs11571319 of the CTLA4 gene were associated with AS (GG vs. AG + AA, p = 0.001). Logistic regression analysis showed that rs201801072 (CD28) and rs11571319 (CTLA4) were independently associated with AS. A significant positive interaction was observed between these SNPs and HLA-B27 positivity, further increasing the risk of AS (T-allele: OR = 6.15; G-allele: OR = 13.30, both p < 0.001). HLA-B27 carriers exhibited an extremely high risk of AS (OR = 65.0, p = 1.19E-06).

Conclusions: The elevated frequencies of specific alleles in AS patients compared to controls highlight the potential involvement of these SNPs as key factors in the pathogenesis of AS, offering new insights into the genetic mechanisms underlying the disease.

Background: Primary immunodeficiencies (PIDs) are a group of diseases that develop as a result of primary or congenital malfunction of the immune system and progress with chronic and/or recurrent bacterial, fungal, protozoal and/or viral infections. In this study, we aimed to examine the effects of the COVID-19 pandemic on depression, anxiety levels and psychological resilience in patients with PID and to compare them with those in controls.

Methods: Seventy patients, aged 18-65 years, who were being followed up with a diagnosis of PID and 69 people as healthy control group, participated in our study. The participants were evaluated cross-sectionally once; sociodemographic data form, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Resilience Scale for Adults (RSA), and COVID-19 Evaluation form were administered to the participants.

Results: HAM-A and HAM-D scores were significantly higher in PID patients compared to controls (HAM-D: 5.5 vs. 3.0, p < 0.001; HAM-A: 6.0 vs. 4.0, p = 0.008). RSA was significantly lower in the patient group (RSA total: 122.5 vs. 136.0, p < 0.001), and pandemic-related risk perception was higher (PRPS: 33.9 vs. 28.3, p < 0.001). Sleep, appetite, and attention-related disturbances were also more common in the patient group. Multivariate regression analyses revealed that PID diagnosis was an independent predictor of increased depression severity (HAM-D), lower psychological resilience (RSA), and greater pandemic-related risk perception. Female sex was independently associated with higher anxiety severity (HAM-A). A personal psychiatric history and greater number of comorbidities were also significant predictors of psychological vulnerability, particularly in relation to depression and anxiety.

Conclusion: Given the observed associations between PID and increased levels of depression, anxiety, and reduced psychological resilience during the pandemic, clinicians may consider heightened vigilance for psychological symptoms in this population during times of public health crisis.

Objective: The purpose of this study was to investigate the predictive relevance of CD27 and CD117 expression and the prognostic value in newly diagnosed multiple myeloma (NDMM) patients.

Methods: This retrospective cohort study analyzed 160 newly diagnosed multiple myeloma (NDMM) patients at Beijing Chaoyang Hospital (2016-2023), evaluating CD27 (TNF receptor family member regulating plasma cell differentiation) and CD117 (c-KIT proto-oncogene product mediating hematopoietic cell survival) expression patterns via pretreatment flow cytometry. Patients were stratified by CD27/CD117 membrane positivity to assess their combined prognostic significance on disease progression, with survival outcomes tracked through standardized clinical surveillance protocols.

Results: The CD27 negative cohort demonstrated severe disease burden, evidenced by elevated β2-MG, increased bone marrow plasma cell infiltration, reduced hemoglobin levels, percentage of high ISS III. Kaplan-Meier analysis demonstrated that CD27 positive cohort showing significantly prolonged median PFS versus CD27 negative counterparts (78 vs. 33 months, P = 0.0078). While CD117 alone lacked prognostic significance, combined CD27(+)CD117(+) status was associated with superior PFS (P = 0.0041 vs. subgroups), earlier ISSMASS staging (P = 0.005, P = 0.021), deeper therapeutic remission rates(Protease inhibitor-based therapy, P = 0.009), and lower frequency of high-risk cytogenetic abnormalities compared to all other combinations, and particularly outperforming CD27(-)CD117(-) patients. Among CD27-expressing patients, CD117 positive patients had better survival performance (P = 0.0424). Multivariate Cox regression confirmed CD27 positivity as an independent protective factor (HR 0.50, P = 0.009) and thrombocytopenia (PLT < 150 × 10⁹/L) as a risk predictor (HR 2.28, P = 0.002), both maintaining significance after adjusting for conventional parameters.

Conclusion: CD27 positive patients have a better prognosis, and the combination of CD27 and CD117 allows refined prognostic risk stratification of MM patients. The expression of CD27 and CD117 is associated with improved prognosis.

Background: Alpha gal syndrome (AGS) is a delayed allergy to red meat, due to IgE to galactose-alpha-1,3-galactose (alpha-gal). Sensitization occurs via tick bites. It has been described in the US, Europe, Australia, Japan and South Korea, but reports from the Indian subcontinent are rare. We report the demographics of alpha-gal allergy for the first time from the Indian subcontinent and possible association with vaccine allergy.

Methods: Patients diagnosed with alpha-gal syndrome (AGS) from 2018 to 2024 were selected in this study. AGS was identified by the occurrence of allergic symptoms up to 8 h of ingestion of red meat, with positive serum IgE to alpha-gal > IgE to red meat, and negative IgE to BSA. Allergy to vaccines containing bovine products were also identified in patients with AGS.

Results: Fifty-seven patients were identified. Thirty-one (54.3%) were 12 years or younger. There were more females among adults (63.2%) compared to children (50.0%), though statistically not significant. There was no difference between children and adults in relation to clinical features and time of onset of symptoms. However, 5/6 of adults with severe anaphylaxis (grade 5) were females. Six patients with AGS developed allergy, including anaphylaxis, to the measles, mumps, rubella (MMR, n = 3), rubella (n = 1), varicella (n = 1) and anti-rabies (n = 1) vaccines.

Conclusion: AGS is an important cause of food and vaccine allergy in the Indian subcontinent and is commoner in children unlike in other regions. However, the clinical features are similar to adults.

Mycobacterium tuberculosis (M. tuberculosis, Mtb) is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis. Macrophages play essential roles in defense against invading pathogens, including M. tuberculosis. The study of M. tuberculosis-associated antigens is one of the hotspots of current research. The secreted proteins of M. tuberculosis, including early secretory antigen target 6 (ESTA6) and culture filtrate protein 10 (CFP-10), are crucial for the immunological diagnosis of tuberculosis. However, the relationship of CFP-10 alone with macrophages is still not well understood. In the present study, we report that the purified recombinant protein CFP-10 (rCFP-10) significantly enhanced the phagocytic capacity of murine macrophages. rCFP-10 induces both TNF-α and IL-6 production. Additionally, RNASeq analysis revealed that rCFP10 triggers multiple pathways involved with macrophage activation. Interestingly, neither mitochondrial reactive oxygen species nor lysosomal content had a significant difference treated with rCFP-10 in macrophages. Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity was shown to significantly reverse the rCFP10-induced phagocytosis, various genes involved in lysosome acidification and TLR signaling. These findings highlight that the CFP-10 plays an essential role in the invasion of macrophages by M. tuberculosis, which is partly regulated by the mTORC2 signal pathway.

Background: This study utilizes the FDA Adverse Event Reporting System (FAERS) database to compare the adverse reaction signals of cyclosporine and tacrolimus, two widely used immunosuppressants, in relation to drug-induced kidney injury. The findings aim to inform clinical decision-making.

Methods: The study retrospectively analyzed data from January 2004 to September 2024, employing both frequency analysis and Bayesian methods. We assessed and compared the mortality rates, hospitalization rates, and the association of cyclosporine and tacrolimus with kidney injury to elucidate the renal toxicity of these two drugs.

Results: After data processing, we identified a total of 3,449 cyclosporine-related kidney injury reports and 5,538 tacrolimus-related kidney injury reports. The results revealed a stronger association between tacrolimus and kidney injury. Additionally, kidney injuries associated with both cyclosporine and tacrolimus predominantly affected males. Furthermore, the hospitalization rate for cyclosporine-related kidney injury was 34.40%, compared to 44.50% for tacrolimus. The mortality rate associated with cyclosporine-induced kidney injury was higher than that of tacrolimus.

Conclusion: This study utilized the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2024 to perform a comprehensive analysis of adverse drug-related kidney injury reactions to cyclosporine and tacrolimus. The results suggest that both cyclosporine and tacrolimus are associated with renal injury, but tacrolimus appears to reduce mortality while increasing hospitalization rates. This serves as a critical warning for planning future treatment regimens, drug monitoring, and reducing adverse effects.

This review comprehensively explores the intricate immune responses within the oral cavity, emphasizing the pivotal role of saliva in maintaining both oral and systemic health. Saliva, a complex biofluid, functions as a dynamic barrier against pathogens, housing diverse cellular components including epithelial cells, neutrophils, monocytes, dendritic cells, and lymphocytes, which collectively contribute to robust innate and adaptive immune responses. It acts as a physical and immunological barrier, providing the first line of defense against pathogens. The multifaceted protective mechanisms of salivary proteins, cytokines, and immunoglobulins, particularly secretory IgA (SIgA), are elucidated. We explore the natural and induced immune responses in saliva, focusing on its cellular and molecular composition. In addition to saliva, we highlight the significance of a serum-like fluid, the gingival crevicular fluid (GCF), in periodontal health and disease, and its potential as a diagnostic tool. Additionally, the review delves into the impact of diseases such as periodontitis, oral cancer, type 2 diabetes, and lupus on salivary immune responses, highlighting the potential of saliva as a non-invasive diagnostic tool for both oral and systemic conditions. We describe how oral tissue and the biofluid responds to diseases, including considerations to periodontal tissue health and in disease periodontitis. By examining the interplay between oral and systemic health through the oral-systemic axis, this review underscores the significance of salivary immune mechanisms in overall well-being and disease pathogenesis, emphasizing the importance of salivary mechanisms across the body.

Immune-checkpoint inhibitors (ICIs) can cause inflammation and immune-related adverse events (irAEs). Although irAEs may be caused by dysregulation of cytokines, the impact of various COVID- 19-related factors on expression of ICI-related AEs remains unclear. Assessment of AEs following ICI administration during the COVID- 19 pandemic may provide valuable insights that enable optimization of patient selection, thereby maximizing the benefits of ICI therapy. The aim of this study was to investigate the actual occurrence of severe AEs after ICI administration during the COVID- 19 pandemic. The medical records of patients who received ICI at Saga University Hospital were examined retrospectively. The primary endpoint was the incidence of all AEs ≥ Grade 3 that occurred after ICI administration. The survey period, from Jan 2020 to Dec 2022, was divided into an earlier (Jan 2020-March 2021) and a later (April 2021-Dec 2022) period. AEs with a clear cause other than ICI were excluded from the analysis. A total of 527 patients were included in the analysis, with a median follow-up of 422 days. During the COVID- 19 pandemic, the incidence of AEs ≥ Grade 3 after ICI administration was 52.8%. The incidence of AEs ≥ Grade 3 AEs after ICI administration was significantly higher during the later period [23.4% (57/244) in the earlier period and 49.8% (236/474) in the later period; mixed effect model p < 0.0001, odds ratio, 3.37 (95% CI: 2.32-4.89)]. Overall survival was significantly worse in the group with AEs ≥ Grade 3 than in the group without AEs ≥ Grade 3 [HR (95% CI) = 0.48 (0.36-0.65), p = 0.0001]. During the COVID- 19 pandemic, it became clear that the incidence of severe AEs (including irAEs) increased after ICI administration, particularly during the later period of the disease. Various factors may be associated with occurrence of severe AEs after ICI administration, and long-term careful observation and prospective multicenter clinical studies are required.

Background: Sepsis, characterized by high morbidity and mortality, necessitates the identification of novel diagnostic and prognostic biomarkers to enhance patient outcomes. Prior research has highlighted the potential clinical utility of long non-coding RNAs (lncRNAs) in sepsis. This study aimed to investigate the clinical significance and underlying mechanisms of serum lncRNA Cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in sepsis.

Methods: Differentially expressed lncRNAs in sepsis patients were explored via GEO database. Sepsis patients and Control subjects were included. An in vitro cellular model was established with LPS-stimulated THP- 1 cells. RT-qPCR assessed CYP1B1-AS1 and miR- 18a- 5p expression. ROC analysis evaluated diagnostic and predictive value. Kaplan-Meier curves and Cox regression analyzed the prognostic value of CYP1B1-AS1. Flow cytometry and ELISA assessed cell apoptosis and inflammatory factors levels. Dual luciferase reporter, RIP, and RNA pull down to validate target binding relationship.

Results: The GSE217700 database shows that CYP1B1-AS1 was upregulated in sepsis. Serum levels of CYP1B1-AS1 were higher in sepsis patients than controls. CYP1B1-AS1 was positively correlated with SOFA and APACHE II scores and distinguished sepsis patients from controls. The 28-day mortality rate for sepsis patients was 29.31%. High CYP1B1-AS1 expression in sepsis patients predicts a worse prognosis and is a potential risk factor. CYP1B1-AS1 targets miR- 18a- 5p. Silencing CYP1B1-AS1 reduced LPS-inducted apoptosis and inflammatory factor promotion, which the miR- 18a- 5p inhibitor reversed.

Conclusion: CYP1B1-AS1 serves as a biomarker for sepsis diagnosis and poor prognosis, potentially promoting inflammation and apoptosis by targeting miR- 18a- 5p.