BMC Immunology最新文献

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.

Introduction: Adalimumab is a monoclonal antibody that is used to treat autoimmune and inflammatory diseases. Biosimilars for adalimumab, including Hyrimoz, have been developed. We aimed to evaluate the effectiveness and adverse effects of Hyrimoz after switching.

Methods: The cohort consisted of patients treated with adalimumab at the Clinical Immunology Outpatient Department of the Erasmus Medical Center between February 2021 and February 2023. Data were collected through electronic patient files and questionnaires sent to the patients. The primary outcome was the number of flares after switching to Hyrimoz, compared to a similar period before the switch. The secondary outcomes were reported adverse effects and patient experience using Hyrimoz.

Results: A total of 185 patients were eligible for inclusion. There was no significant difference in the occurrence of flares between Humira and Hyrimoz (P = 0.456). Forty-six of the 185 patients reported adverse effects (24.9%). A total of 25/185 (13.5%) patients reported pain during injection, which was the most frequently reported adverse effect. During the course of this study, 60/185 (32.4%) patients discontinued Hyrimoz treatment because of flares (n = 17 [9.2%]), adverse effects (n = 27 [14.6%]), or more subjective complaints (n = 15 [8.1%]) related to the underlying disease. One patient discontinued treatment because of inactive disease.

Conclusion: The number of flares before and after switching to Hyrimoz was comparable. However, adverse effects and increased subjective complaints have been reported after switching to this new biosimilar.

Background: Having psoriasis in hard-to-treat areas, such as the scalp, face, palms, soles, nails, and genitals, can suffer from a reduced quality of life. This study was designed to investigate the prevalence and risk factors of hard-to-treat body locations of psoriasis, and to describe patients' clinical and demographic characteristics, and quality of life impacts.

Methods: We conducted a multicenter observational epidemiological study involving over 1000 hospitals in China, enrolling a total of 7032 psoriasis patients. Groups were compared to patients without involvement of hard-to-treat areas.

Results: The most frequently affected hard-to-treat area was the scalp (60.01%), followed by the face (22.47%), nails (18.87%), palms or soles (18.23%), genitals or vulvas (12.00%), respectively. Among all patients, 70.71%, 36.65%, 16.30%, 6.48% and 1.45% of patients had involvement of ≥ 1, ≥2, ≥ 3, ≥4 or ≥ 5 hard-to-treat areas. There was a male predominance among patients with involvement of at least one hard-to-treat area(P < 0.001). The smoking rate, BMI (body mass index) and psoriasis family history in patients with at least one hard-to-treat area involvement were significantly higher than those in patients without hard-to-treat area involvement (P < 0.001), especially among patients with nail involvement. With regards to current DLQI (dermatology life quality index), satisfactory rate, and current BSA (body surface area), these findings were all significantly different (P < 0.001) when compared to patients without involvement of a hard-to-treat area. Notably, even in mild-to-moderate psoriasis (BSA < 10), 65.10% of patients showed involvement of ≥ 1 hard-to-treat area, with significant impacts on quality of life (DLQI increase, all P < 0.001) and treatment satisfaction (P < 0.001 vs. non-involved).

Conclusion: Psoriasis commonly affects hard-to-treat locations, even in patients with mild to moderate disease (BSA < 10). The disproportionate impact on quality of life (particularly genital/face involvement) and treatment satisfaction underscores the need for: (1) routine assessment of these areas regardless of BSA, and (2) targeted management of modifiable risk factors (smoking, obesity). These findings support incorporating hard-to-treat area evaluation into psoriasis severity assessments and treatment algorithms.

Brucella is a common kind of bacteria that has the ability to live within cells and may cause diseases that can be transmitted between animals and humans. Current medical therapy struggles to effectively eradicate Brucella. Thus, it is necessary to develop a multi-epitope vaccine (MEV) in order to effectively prevent Brucella infection. To achieve this objective, we used the reverse vaccinology methodology based on omp19 and Bacterial surface antigen (D15). After conducting our research, we successfully identified 2 cytotoxic T lymphocyte (CTL) epitopes, 2 helper T lymphocyte (HTL) epitopes, and 2 linear B cell epitopes from Omp19 and Bacterial surface antigen (D15). These epitopes will be further examined in our study. In order to maintain the proper folding of the protein, we connected GGGS and EAAAK consecutively. Adjuvants are added to the N-terminal of the vaccine peptide to boost its immunogenicity. In order to assess the immunity, stability, protection, and practicality of the final MEV, a construct consisting of 387 amino acids was created by connecting linkers and adjuvants. Furthermore, molecular docking and simulations using molecular dynamics were conducted to confirm the binding strength and durability of the MEV-TLR5. Subsequently, codon adaptation and in silico cloning analyses were conducted to determine the potential codons for expressing the MEV. The findings indicated that the MEV exhibited a significant level of immunogenicity. This work has collectively established a theoretical foundation for the development of a vaccine against Brucella.

Background: Inflammatory bowel disease (IBD) management remains challenging due to limited preventive strategies and the low bioavailability of therapeutic agents like resveratrol (RSV). While RSV exhibits anti-inflammatory properties, its preventive potential via gut microbiome modulation remains unexplored.

Methods: A murine colitis model was established using 2.5% DSS, with mice randomized into control (CON), DSS, therapeutic RSV treatment (RSV), and preventive RSV treatment (PRE) groups. Clinical outcomes, intestinal barrier integrity, inflammatory cytokines, macrophage polarization, TLR4/NF-κB signaling, and gut microbiota (16S rRNA sequencing) were systematically evaluated.

Results: Preventive RSV (PRE) outperformed therapeutic RSV across all metrics. PRE attenuated colitis severity by 51.4% (weight loss, P < 0.001 vs. RSV) and restored mucosal architecture (P = 0.048 vs. DSS). Mechanistically, PRE normalized barrier function via transcriptional (ZO-1: 56.7% of CON; Occludin: 14-fold induction vs. DSS) and protein-level recovery (ZO-1: 96.5% of CON, P = 0.02), suppressed pro-inflammatory cytokines (TNF-α: 80.8%; IL-6: 69.9%; IL-18: >96%, P < 0.001 vs. DSS), and promoted M2 macrophage polarization (CD206: 1.7-fold vs. CON, P = 0.02) through TLR4/NF-κB inhibition (53% TLR4 reduction vs. 15% with RSV, P < 0.001). Despite comparable α-diversity between RSV and PRE, PRE uniquely enriched barrier-protective taxa (Lactococcus, Muribaculum) and restored microbial amino acid biosynthesis. Crucially, PRE's efficacy despite low systemic bioavailability implicated microbiome-mediated "luminal priming" as its primary mechanism.

Conclusions: This study redefines preventive RSV as a microbial ecosystem engineer that preemptively fortifies the gut against inflammation via microbiome-immune-metabolic crosstalk. By prioritizing ecological prevention over symptom suppression, our findings offer a transformative "food as medicine" strategy for IBD, highlighting RSV's potential as a chronotherapeutic agent to reshape clinical paradigms.