BMC Immunology最新文献

Introduction: Antivimentin/cardiolipin antibodies (aVim/CL) have emerged as potential diagnostic markers for antiphospholipid syndrome, However, their association with pregnancy outcomes remains unclear. This study explores the clinical significance of aVim/CL in pregnancy loss.

Methods: A retrospective analysis was conducted on 429 pregnant women with at least one spontaneous miscarriage at The Third Affiliated Hospital of Wenzhou Medical University (October 2019- August 2022). Multivariable logistic regression and stratified analyses were utilized to assess the relationship between aVim/CL levels and pregnancy loss.

Results: Among the 429 participants, 79 experienced pregnancy loss, while 350 had live births. Elevated aVim/CL levels were associated with an increased risk of pregnancy loss, with an odds ratio (OR) of 1.108 (95% CI, 1.037-1.185). The area under the ROC curve (AUC) was 62.8, with a sensitivity of 77.2% and a specificity of 44%. A nonlinear L-shaped relationship was identified, with a threshold of 6.86 ng/mL, below which the risk of pregnancy loss significantly increased. No correlations were found between aVim/CL and coagulation or immune biomarkers.

Discussion: Elevated aVim/CL levels were identified as independent predictors of pregnancy loss in women with a history of spontaneous miscarriage. The threshold of 6.86 ng/mL may provide valuable clinical insights for risk stratification.

Objective: The aim of this study was to evaluate the diagnostic value of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels in multiple sclerosis (MS) and optic neuromyelitis optica spectrum disorders (NMOSD) and their relationship with disease prognosis by Meta-analysis, and to explore their potentials in early diagnosis of the disease and monitoring of its course.

Methods: We systematically searched China National Knowledge Infrastructure (CNKI), VIP database, Wanfang database, PubMed, Wiley online library, and web of science databases for relevant literature on GFAP in neuroimmune diseases, and the time limit for searching was from inception to December 1, 2024, and two evaluators independently assessed all the studies. Two evaluators independently assessed the quality of all the studies, evaluated the data in detail according to the criteria of risk of bias, and performed Meta-analysis using RevMan 5.4.1 software and STATA 18.

Results: Through literature screening, 12 studies were finally included, involving a total of 1731 participants, of which 871 were in the control group and 869 were in the experimental group. Meta-analysis results showed that GFAP levels in MS patients were significantly higher than those in healthy control groups [MD = 0.98, 95% CI (0.70, 1.25), P < 0.0001]; NfL levels were also significantly higher than controls [MD = 0.76, 95% CI (0.06, 1.46), P = 0.03]. In patients with optic neuromyelitis optica spectrum disease (NMOSD), GFAP levels were significantly higher than controls [MD = 0.97, 95% CI (0.03, 1.91), P = 0.04]; NfL levels were also significantly higher than controls [MD = 0.24, 95% CI (0.02, 0.46), P = 0.03]. Analysis of different disease stages showed that compared with healthy controls, GFAP levels were significantly elevated in patients with MS in the deteriorating phase [MD = 2.38, 95% CI (1.40, 3.37), P < 0.0001], in the active phase [MD = 2.01, 95% CI 0.20, 3.82), P = 0.03], and in the remission phase at a lower level of elevated GFAP levels [MD = 1.33, 95% CI (0.20, 2.46), P = 0.02]. For GFAP survival analysis in MS patients, the results showed no statistical significance [HR = 1.78, 95% CI (0.47, 6.66), P = 0.39].

Conclusion: The levels of GFAP and NfL in MS and NMOSD patients were significantly higher than those in healthy controls. GFAP levels demonstrate a progressive decline correlating with MS disease activity-from exacerbation through active to remission phases-yet remain persistently elevated compared to controls. These findings indicate its potential utility for MS diagnosis and disease monitoring.

Background: Complete complement factor I (CFI) deficiency is an inborn error of immunity (IEI) that results in heightened susceptibility to infections and immune dysregulatory disorders. This systematic review seeks to enhance our understanding of the clinical characteristics, genotype-phenotype correlations, and treatment outcomes in patients with complete CFI deficiency, including three novel cases. We conducted a comprehensive literature review of cases published from 1996 to November 2024, identifying 49 patients with homozygous or compound heterozygous mutations in the CFI gene.

Results: Among the 49 patients, the mean age at initial presentation was 7.19 (± SD: 9.75) years. Most patients presented with infectious manifestations (n: 37, 75.5%), particularly sepsis (n: 18, 36.7%). The predominant pathogens were encapsulated organisms, particularly Neisseria meningitidis. Immune dysregulatory manifestations involved rheumatologic (n: 14, 28.57%), neurologic (n: 11, 22.4%), and renal (n: 8, 16.3%) disorders. Immunological evaluations showed low or absent levels of C3 and CFI in most patients. Genetic analysis identified 45 distinct mutations; less deleterious mutations, such as missense and splicing variants, were more common in those with immune dysregulation. Notably, three patients treated with eculizumab demonstrated significant clinical improvement.

Conclusion: Complete CFI deficiency presents a varied clinical spectrum, from asymptomatic to recurrent infections and immune dysregulation. Early diagnosis and targeted therapies, such as eculizumab, may improve patient outcomes. These findings underscore the necessity for further research into the nature of complete CFI deficiency and the development of optimal management strategies.

Objective: To examine whether pidotimod affects the progression and severity of experimental autoimmune encephalomyelitis (EAE), a classic animal model of multiple sclerosis (MS), the balance of splenic lymphocytes in pidotimod-treated and untreated EAE mice was examined.

Methods: C57BL/6J mice were immunized by subcutaneous injection of an emulsion containing MOG35-55, with subsequent monitoring of their general condition and clinical scores following treatment with pidotimod or saline solution (vehicle control). Hematoxylin and eosin (H&E) staining, along with flow cytometry (FCM), was employed to evaluate leukocyte infiltration, while FluoroMyelin™ Green staining was utilized to assess axonal demyelination in the central nervous system (CNS). Additionally, FCM was conducted to investigate the effects of pidotimod on splenic lymphocytes both in vitro and in vivo during the peak stage of EAE.

Results: Compared to the vehicle control, pidotimod treatment significantly reduced the clinical scores, decreased leukocyte infiltration in the spinal cord and brain, and suppressed demyelination in the spinal cord. Furthermore, pidotimod treatment markedly increased the populations of CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells (Tregs) and CD8⁺ Foxp3⁺ Tregs, while decreasing the numbers of CD4⁺ IFN-γ⁺ helper T cells (Th1), CD4⁺ IL-17⁺ helper T cells (Th17), and CD8⁺ IL-17⁺ cytotoxic T cells (Tc17) in the spleen during the peak stage of EAE both in vitro and in vivo. Additionally, pidotimod treatment significantly diminished the population of B220⁺ TNF-α⁺ B cells in the spleen at the peak stage of EAE both in vitro and in vivo.

Conclusions: The present study preliminarily explored the effects and potential immunomodulator mechanisms of pidotimod in treating EAE mice. Results indicated that pidotimod treatment decreased the percentages of CD4⁺ IFN-γ⁺ Th1 cells, CD4⁺ IL-17⁺ Th17 cells, CD8⁺ IL-17⁺ Tc17 cells and B220⁺ TNF-α⁺ B cells, while increasing the percentages of CD4⁺ CD25⁺ Foxp3⁺ Tregs and CD8⁺ Foxp3⁺ Tregs in the spleen at the peak stage of EAE. Additionally, pidotimod reduced leukocyte infiltration into the spinal cord and brain, as well as demyelination in the spinal cord. These findings suggest that the neuroprotective effects of pidotimod in EAE mice may be its ability to regulate the balance of splenic lymphocytes.

Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare inborn error of immunity, characterised by immunodeficiency and immune dysregulation. Having only been recognised in 2013, evidence on APDS is limited. We carried out four systematic literature reviews (SLRs) to identify and narratively synthesise evidence on the following for APDS: epidemiology (epidemiology SLR), clinical efficacy/safety of treatments (clinical SLR), cost-effectiveness and costs/healthcare (HCRU) associated with (economic SLR) and health-related quality of life (HRQoL) and utility data (HRQoL SLR) from a global perspective.

Methods: The Cochrane Collaboration and the University of York's Centre for Reviews and Dissemination (CRD) guidelines were followed. MEDLINE, Embase, the Cochrane Library, University of York CRD, conference proceedings and other grey literature were searched through to May 2023 for all SLRs, except the epidemiology SLR (searched to Nov 2021); economic databases were also searched for the economic and HRQoL SLRs. Eligible records were: primary epidemiology publications (epidemiology SLR), interventional/observational studies of treatments (clinical SLR), cost/HCRU studies/economic evaluations (economic SLR) and HRQoL/utility studies (HRQoL SLR) in people with APDS. Risk of bias was assessed using the Downs and Black checklist (clinical SLR) and the Drummond checklist (economic SLR).

Results: The numbers of unique relevant studies identified were: 0 (epidemiology SLR), 117 (clinical SLR; 87 reported on <5 patients), 2 (economic SLR) and 1 (HRQoL SLR). The clinical SLR reported symptomatic treatments to be only partially effective at controlling APDS manifestations, with variable tolerability. Outcome reporting was heterogeneous and inconsistent, with small sample sizes and patients receiving multiple treatments, limiting interpretation of results. The economic SLR reported a high direct cost of APDS. Additional HRQoL/utility studies are required to evaluate the clinical and HRQoL burden of APDS and the impact of therapies.

Conclusion: Four methodologically robust SLRs identified limited evidence on epidemiology, clinical outcomes, costs and HRQoL in APDS, reflecting its ultra-rare nature and recent recognition. This suggests a need for more rigorous data evaluating the clinical and economic effectiveness of APDS treatments. Outcome reporting was highly heterogeneous and inconsistent across studies, sample sizes were small and patients often received multiple treatments, limiting interpretation of results.

Background: Psoriasis, an inflammatory autoimmune disease, arises from intricate interactions between the immune system and epithelium. Recent reports have suggested new roles for gamma delta (γδ) T-cells in addition to immune surveillance, however, it remains to be determined whether the mechanisms identified in psoriasis murine models have a similar role in humans. The aim of the present study was to investigate the relationship between IL-17 A mRNA expression levels and γδ T-cell frequency in human psoriatic lesions, and to clarify the potential role of γδ T-cells in psoriasis pathogenesis.

Methods: The study involved 20 patients diagnosed with psoriasis and 16 control subjects. Expression of the IL-17 A gene was measured in formalin-fixed paraffin-embedded (FFPE) tissues by RT-PCR method. TCRγδ⁺ immunofluorescence staining was performed to measure the distribution of γδ T-cells in the same samples.

Results: In psoriatic lesion biopsies, TCRγδ⁺ T-cell percentage was found higher than the control samples. Additionally, psoriasis patients exhibited elevated levels of IL-17 A gene expression. In addition, this study showed a weak negative correlation between the proportion of γδ T-cells and IL-17 A mRNA expression in psoriatic skin samples.

Conclusion: A weak negative correlation between IL-17 A mRNA levels and γδ T-cell presence in human psoriasis lesions highlighting the novel effector functions of these cells in psoriasis pathogenesis.

Aims: The Inflammatory response plays an important role in the pathophysiology and prognosis of ischemic stroke. Hyperinflammation progresses with aggravation of brain damage and deterioration in clinical status. The study aimed to demonstrate a valuable, easy-to-obtain, and inexpensive parameter for prognostic assessment by comparing the Pan-immune Inflammation Value (PIV), Systemic Immune-Inflammation Index (SII), and CALLY scores in patients with ischemic stroke.

Methods: In this retrospective single-center cohort study, the files of patients who were followed up with a diagnosis of ischemic stroke in the tertiary intensive care units. Multivariate regression analysis and receiver operating characteristic curves(ROC) were used to detect the association between PIV, SII, and CALLY on in-hospital mortality and their superiority over each other in predicting mortality in ischemic stroke patients.

Results: Of 1,039 patients, 453 died, resulting in an overall survival rate of 56.4%. In the multivariate analysis, high APACHE II scores and low albumin levels remained independent risk factors. ROC curves showed that PIV, SII, and CALLY exhibited good predictive values, with AUCs of 0.921, 0.887, and 0.930 (95% CI: 0.903-0.936, 0.855-0.896, 0.913-0.945; p < 0.001). A pairwise comparison of the data based on AUC values indicated a significant difference between SII and both PIV and CALLY (p < 0.001). In contrast, no significant difference was found between PIV and CALLY (p = 0.385).

Conclusion: The PIV, SII, and CALLY indices serve as accessible and reliable prognostic biomarkers that can enhance personalized treatment strategies and improve clinical decision-making in patients with ischemic stroke.

The tumor necrosis factor (TNF) ligand superfamily plays a critical role in immune regulation and has emerged as a promising target in cancer immunotherapy. By binding to its receptor OX40 (CD134), TNFSF4 promotes the proliferation and survival of T cells and plays an important role in the tumor immune microenvironment, but its role in pancreatic cancer is unclear. This study aimed to investigate the expression patterns and prognostic significance of TNF ligand family members in pancreatic cancer (PC), with a specific focus on TNFSF4. We analyzed single-cell RNA sequencing data from the GSE212966 dataset to assess the expression of TNFSF ligands across immune cell types. TCGA-PAAD bulk RNA-seq data were used for non-negative matrix factorization (NMF) clustering to identify molecular subtypes based on TNFSF ligand expression profiles. Immune infiltration was quantified using single-sample gene set enrichment analysis (ssGSEA), and Kaplan-Meier survival curves were used to compare overall survival (OS) and progression-free survival (PFS) between subtypes. Immunotherapy response prediction was evaluated using tumor mutational burden (TMB), immunophenoscore (IPS), and tumor immune dysfunction and exclusion (TIDE) scores. Gene expression validation was performed using qRT-PCR. TNFSF ligands were predominantly expressed in antigen-presenting cells, particularly B cells and macrophages. NMF clustering identified two molecular subtypes of PC, with cluster 2 associated with significantly better OS and PFS (p < 0.05). TNFSF4, highly enriched in B cells, was found to regulate immune-related pathways such as B cell receptor signaling and cytokine-cytokine receptor interaction, as revealed by KEGG pathway analysis. TNFSF4 expression also correlated with favorable immunotherapy markers, suggesting its potential role as a predictive biomarker. These findings were supported by qRT-PCR validation. This study provides a TNFSF ligand-based molecular classification of pancreatic cancer and highlights the immunoregulatory role of TNFSF4. Its association with patient prognosis and immunotherapy responsiveness suggests potential clinical utility in guiding treatment strategies.