BMC Immunology最新文献

Background: Brain metastasis (BM) remains a major therapeutic challenge in non-small cell lung cancer (NSCLC) without actionable driver mutations. Radiotherapy combined with immune checkpoint inhibitors (ICIs) may enhance intracranial control through synergistic immune activation. This study evaluated the efficacy of radiotherapy plus ICI and explored prognostic factors influencing outcomes in patients with NSCLC-BM.

Methods: We retrospectively analyzed 116 patients with measurable, driver-negative NSCLC-BM treated between June 2019 and December 2024. Patients were divided into two groups: Radiotherapy combined with ICI plus chemotherapy (RT + ICI, n = 56) and ICI plus chemotherapy (ICI, n = 60). Intracranial and systemic objective response rates (iORR, sORR) and progression-free survival (iPFS, sPFS) were analyzed. Prognostic factors, including the prognostic nutritional index (PNI), were assessed using Cox regression analyses.

Results: Compared with the ICI group, the RT + ICI group demonstrated a significantly higher iORR (78.6% vs 40.0%, P < 0.001) and significantly longer median iPFS (11.8 vs 7.9 months; hazard ratio [HR] = 0.48, 95% confidence intervals [CI] 0.30-0.77, P = 0.002), and sPFS (8.9 vs 5.9 months; HR = 0.58, 95% CI 0.38-0.89, P = 0.014). High PNI (≥ 42.15) was independently associated with prolonged iPFS (HR = 8.77, 95% CI 2.91-26.47, P < 0.001) and sPFS (HR = 8.46, 95% CI 3.39-21.10, P < 0.001).

Conclusion: Radiotherapy combined with immunochemotherapy was associated with improved intracranial and systemic outcomes compared to immunochemotherapy alone in patients with driver-negative NSCLC-BM. Additionally, PNI shows potential as a useful biomarker for predicting therapeutic outcomes.

Background: The diversity of clinical symptoms of neonatal sepsis leads to difficulties in diagnosis, and the treatment is limited. This study aims to investigate the role of the SIRT1/miR-223 signaling axis in neonatal sepsis.

Methods: 100 neonates with sepsis and 100 healthy infants were included in this study. The RT-qPCR was used to detect RNA and inflammatory factor levels in serum. Peripheral blood neutrophils were isolated by gradient centrifugation. LPS-stimulated neutrophils were detected for MPO activity and inflammatory factor expression. Neutrophils were transfected with miR-223 oligonucleotide and SIRT1-related plasmid to detect changes in neutrophil-related parameters.

Results: Neonates with sepsis had a significantly stronger inflammatory response than healthy infants, and the expression of miR-223 and SIRT1 in the serum was remarkably reduced. ROC curves showed that miR-223 had a diagnostic value for neonatal sepsis. The expression of miR-223 and SIRT1 was notably reduced in the model cells, and overexpression of miR-223 attenuated the inflammatory response in the LPS-induced neutrophil. Overexpression of SIRT1 could alleviate the enhanced inflammatory response due to inhibition of miR-223.

Conclusion: Overexpression of SIRT1 upregulated miR-223 expression, which attenuated the LPS-induced neutrophil activity and inflammatory response. The SIRT1/miR-223 signaling axis provides a potential therapeutic target for the clinical management of neonatal sepsis.

Background: Autoimmune hepatitis (AIH) is a chronic liver disease in which the immune system of the body unintentionally targets liver cells, resulting in inflammation, liver damage, and cirrhosis if treatment is not received. Although the precise origin of AIH remains unknown, experts believe that environmental and genetic factors play significant roles in its pathogenesis. This study describes the clinical, biochemical, and long-term outcomes of patients with autoimmune hepatitis (AIH) at the Science and Technology Hospital in Sana'a, Yemen.

Methodology: This was a retrospective, single-center study.

Participants: All patients with AIH diagnosed at the Science and Technology Hospital between 2019 and 2024 were included.

Results: Most patients were male (18 of 25, 72%). All patients displayed common signs and symptoms of AIH, including hepatomegaly, vomiting, jaundice, and abdominal distention. In addition to positive antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), the majority of individuals showed increased AST levels. The most prevalent hematological abnormalities were thrombocytopenia (64%) and anemia (56%). Regarding the outcome after hospital admission, 60% of cases improved, 12% were discharged against medical advice, 8% died, and 20% had unknown outcomes.

Conclusion: Autoimmune hepatitis affects patients of Yemeni descent. The most common symptom is jaundice. Only Type I AIH was observed in this cohort, and the mortality rate reached 8%.

Background: We investigated whether the ratio of lactate dehydrogenase (LDH) to albumin could be used as a diagnostic marker for Behçet's disease compared to the healthy population and as a marker to assess the severity and activity of the disease.

Methods: The research was conducted as a cross-sectional study. Patients aged 18-69 years presenting to the Behçet's disease Outpatient Clinic over a three-year period and healthy individuals with a similar age and gender distribution formed the two study groups. LDH and albumin levels, and the LDH/albumin ratio were compared between the groups.

Results: The study was conducted in 349 people, 160 patients with Behçet's disease and 189 healthy controls. The LDH/albumin ratio was significantly higher in the Behçet's group than in the control group. This ratio was significantly different according to the severity of the disease, the presence of genital ulcers, papulopustular lesions and joint involvement (p < 0.05). Duration of symptoms was positively correlated with LDH/albumin ratio values (r = 0.259, p = 0.001). ROC analysis of the LDH/albumin ratio in the severe versus not severe groups based on Behçet's disease severity showed an area under the curve (AUC) of 0.704 (95% CI: 0.586-0.821) and a cut-off value of 57.46, with a sensitivity of 57.7% and specificity of 72.4%.

Conclusion: The LDH/albumin ratio is a promising parameter in patients diagnosed with Behçet's disease compared to healthy controls, with a cut-off value of 57.46 for distinguishing severe from non-severe disease.

Trial registration: This study was registered under ID number NCT06276829 (Study Record Dates:18.02.2024).

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health burden due to latent infection, multidrug resistance, and the limited efficacy of the BCG vaccine. To address this challenge, we computationally designed and evaluated a circular mRNA-based multi-epitope vaccine candidate, TZ1391. Five experimentally validated M. tuberculosis antigens (ESAT-6, CFP-10, Ag85B, PPE18, and HspX) were used to predict immunodominant cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes. Three vaccine constructs (MTB-C1, MTB-C2, and MTB-C3) were assembled by integrating 20 CTL, 20 HTL, and 20 B-cell epitopes with appropriate linkers, PADRE sequence, and innate immune adjuvants. Structural modeling using AlphaFold2 and GalaxyRefine confirmed stable, native-like conformations for all constructs, with MTB-C3 showing the highest structural quality (GDT-HA = 0.8782; RMSD = 0.646 Å) and the greatest number of stabilizing disulfide bonds. Molecular docking against TLR3, TLR4, and TLR8 identified two top-performing candidates. MTB-C3 exhibited the strongest interaction with TLR3, achieving the lowest HDock score (- 480.53) and highest confidence score (0.9987), while MTB-C2 showed optimal binding to TLR4 (ClusPro score - 1488.6; confidence 0.9700). Despite favorable TLR4 engagement by MTB-C2, MTB-C3 was prioritized as the lead candidate (TZ1391) due to its superior structural stability, reduced conformational fluctuations during molecular dynamics simulations, and stronger TLR3 binding free energy (ΔG_bind = - 173.25 ± 7.9 kcal/mol). Immune simulations further predicted that TZ1391 elicits a robust Th1-biased response, characterized by sustained IgG production, strong IFN-γ and IL-2 induction, and durable immune memory. Overall, the strong TLR3-mediated interaction, combined with enhanced structural stability and favorable immunogenic profiles, establishes TZ1391 as a promising multi-epitope vaccine candidate for further experimental validation against tuberculosis.