Immunologic Research最新文献

SALL4 is aberrantly reactivated in multiple malignancies, including breast cancer (BC), where it promotes tumor progression and therapy resistance. However, its therapeutic targeting remains underexplored. This study investigates the antitumor efficacy of a novel SALL4-inhibitory peptide, PEN-FFW, and its regulatory impact on the PI3K/AKT/PD-L1 axis and CD8⁺ T cell-mediated cytotoxicity in BC. SALL4 expression in BC was assessed using public databases and validated in cell lines by RT-qPCR and western blot. The interaction between SALL4 and the NuRD complex was evaluated by co-immunoprecipitation assay. Functional assays were conducted to assess the effects of PEN-FFW in vitro. Co-culture systems were used to evaluate CD8⁺ T cell-mediated cytotoxicity. Mechanistic studies investigated the involvement of the PTEN/PI3K/AKT/mTOR signaling axis. In vivo efficacy was tested in allograft mouse models, including combination therapy with anti-PD-L1 antibody. SALL4 was significantly upregulated in BC and associated with poor prognosis. PEN-FFW disrupted the SALL4-NuRD interaction, restored PTEN expression, and suppressed PI3K/AKT/mTOR signaling. This led to a reduction in PD-L1 expression and increased apoptosis, while inhibiting the proliferation and migration of BC cells. PEN-FFW also enhanced CD8⁺ T cell cytotoxicity by reducing PD-L1-mediated immune evasion. Furthermore, combination treatment with PEN-FFW and anti-PD-L1 antibody showed superior tumor suppression and increased CD8⁺ T cell infiltration compared to either treatment alone. PEN-FFW is a potent SALL4-inhibitory peptide that suppresses BC progression by downregulating PD-L1 through PI3K/AKT pathway inactivation and promoting CD8⁺ T cell-mediated tumor killing. These findings highlight a promising strategy for enhancing immunotherapy in SALL4-positive BC.

The lectin pathway, activated by ficolins, contributes to systemic lupus erythematosus (SLE) pathogenesis, but ficolin data remain inconsistent across populations. Present muti-centric cross-sectional study assessed serum ficolin-1, -2, and - 3 levels and their associations with clinical features and disease activity among SLE patients from five Indian regions (Mumbai, Assam, Meghalaya, Manipur, and Nagaland). Serum levels of ficolin-1, ficolin-2, and ficolin-3 were measured using ELISA. Disease activity was assessed using the SELENA-SLEDAI score. Statistical analyses were performed using non-parametric tests, with p < 0.05 considered significant. Serum ficolin levels differed significantly by region. Ficolin-1 and ficolin-2 levels were positively correlated with the renal involvement in SLE patients from Mumbai (r = 0.218; p < 0.001 and r = 0.199; p = 0.001, respectively), while ficolin-1 levels were also correlated with lupus nephritis (LN) in SLE patients from Manipur (r = 0.247; p = 0.040). In Assam, ficolin-2 levels were significantly reduced in patients with mucocutaneous manifestations (r=-0.258; p = 0.014), and ficolin-3 levels showed a negative correlation with musculoskeletal manifestations (r=-0.217; p = 0.040). In Mumbai, ficolin-1 levels were positively associated with disease activity (r = 0.139; p = 0.018), and ficolin-3 levels correlated positively with anti-dsDNA autoantibodies (r = 0.172; p = 0.004). Conversely, ficolin-3 levels showed a negative correlation with anti-dsDNA (r=-0.470; p < 0.001) in Assam. The present study demonstrated significant regional variations in ficolin levels among SLE patients across India. Association of ficolin-1 and ficolin-3 with specific organ involvement suggested their potential as possible immunological indicators in SLE. These findings suggested the importance of considering regional and ethnic differences in SLE management and warranted further validation through larger, longitudinal studies.

IHP is a rare inflammatory disorder characterized by dural thickening. Its nonspecific presentation often leads to diagnostic challenges and potential misdiagnosis as a neoplasm. Literature review and illustrative case example. PubMed search using terms related to IHP yielded 272 candidate citations, 50 of which met study criteria and were included. A 40-year-old woman presented with headache, dizziness, and blurred vision. Surgical intervention via right craniotomy was recommended due to diagnostic uncertainty, symptomatic mass effect, and the potential for a malignant diagnosis. A near-total resection of the mass and its dural base was performed given the involvement of the transverse-sigmoid sinuses; histopathology revealed dense fibrous tissue with chronic inflammatory cell infiltration. Immunohistochemistry was positive for CD3 and CD20, and negative for EMA, SSTR2, IgG, and IgG4, confirming the diagnosis of IHP. Review of the literature identified 117 patients presenting at a median age of 51 years with slight female predominance. Headache was the most common symptom (94%), followed by cranial nerve deficits (49%). MRI was used in all cases, with the tentorium being the most frequent site of involvement (48%). Treatment typically involved biopsy (47%), resection (11%), long-term steroids (56%), or steroid taper (44%). Radiographic recurrence was observed in 35%. Based on the experience from our case and supportive summative evidence from the literature, we developed a clinical decision-making schema to assist clinicians in recognizing and managing IHP. IHP remains a diagnostic challenge due to its rarity, nonspecific presentation, and potentially confounding radiographic features.

Current biologics and small-molecule inhibitors for autoimmune diseases often provide symptomatic relief but fail to restore immune tolerance, necessitating lifelong treatment with associated risks. Triptolide, a natural compound from Tripterygium wilfordii Hook F, exhibits a unique capacity for immune reprogramming, simultaneously suppressing pathogenic immunity while enhancing regulatory functions, positioning it as a potential 'immune reset' agent. However, its clinical translation is plagued by a narrow therapeutic window due to mechanism-based toxicity, creating a critical challenge of decoupling efficacy from toxicity. This review moves beyond a descriptive cataloguing of triptolide derivatives to provide a critical appraisal of the field's progress in achieving this decoupling. We systematically evaluate the most promising candidates (e.g., LLDT-8, Minnelide, ZT01), not only examining their mechanisms but also analyzing why most stall in early development. By integrating mechanistic insights with clinical progress data, we dissect the structural determinants of toxicity and efficacy and propose a concrete future roadmap focused on rational drug design (e.g., novel targets like TAK1), targeted delivery systems, and biomarker-driven precision medicine to advance safe and effective triptolide-based therapies to the clinic.

This systematic review and meta-analysis assess the immunogenicity and maternal-fetal safety profile of RSV prefusion F (RSVpreF) vaccination during pregnancy. PubMed, Scopus, Embase, Cochrane, and Web of Science databases were searched for relevant studies. Only randomized controlled trials (RCTs) evaluating the safety, efficacy, and immunogenicity of RSVpreF vaccination in pregnant women were included. Six RCTs, involving 17,212 participants, were analyzed. The vaccine significantly boosted maternal anti-RSV neutralizing antibody levels, with a standardized mean difference (SMD) of 1.40 for RSV-A and 1.11 for RSV-B, both with high statistical significance. Infants born to vaccinated mothers had a 49% reduced risk of RSV-associated lower respiratory tract illness within 180 days post-vaccination (OR = 0.51, 95% CI: 0.40-0.64). Preterm birth rates did not differ significantly between the vaccine and placebo groups (OR = 1.09, 95% CI: 0.87-1.37). The vaccine was not associated with increased risks of serious adverse events or perinatal complications. Maternal RSVpreF vaccination significantly elevates neutralizing antibody levels against RSV subtypes A and B without increasing the risk of serious adverse events or preterm delivery. These findings support the safety and immunogenicity of RSV vaccination in pregnant women, reinforcing its potential utility in protecting neonates against RSV-related morbidity.

Background Kawasaki disease shock syndrome (KDSS) is a severe form of Kawasaki disease (KD). The serum lipid has been proposed to be valuable in predicting shock syndrome in clinical circumstances; however, limited data is available in KDSS patients. Therefore, we prospectively evaluated the ability of serum lipid in predicting KDSS. Methods A total of 1009 KD patients aged 2 months to 139 months were enrolled in this prospective cohort study between June 2017 and April 2022. The demographic/clinical characteristics and laboratory data were compared between the patients with KDSS (KDSS group) and those without (KD group). Multivariate logistic regression analysis was utilized to determine the correlation between serum lipid and KDSS. Receiver operating characteristic (ROC) curve analysis was subsequently performed to assess the validity of serum lipids in predicting KDSS. Results Except for triglyceride (TG), almost all the levels of detected lipid profiles were significantly lower in the KDSS subjects compared to non-KDSS patients. In terms of KDSS prediction, the cut-off values of 2.845 mmol/L, 0.355 mmol/L, 1.405 mmol/L, 0.595 g/L, and 0.805 g/L for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo A) and apolipoprotein B (Apo B), yielded sensitivities of 80%, 68%, 64%, 76% and 88%, with specificities of 69%, 93%, 89%, 83% and 51%, respectively. Conclusions Lipid profiles were robustly dysregulated in KDSS patients. Noticeably, serum lipid was a complementary laboratory marker for KDSS prediction.

Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI) characterized by a defective respiratory burst in phagocytes and defective clearance of phagocytosed microorganisms. CGD is caused by a defect of the enzyme NADPH oxidase, resulting in severe and life-threatening infections in affected children. The genetically heterogeneous X-linked recessive form of CGD (XL-CGD) is caused by mutations in the CYBB gene. XL-CGD is typically diagnosed early in life, usually before the age of 3 years. The present report describes a boy aged 9 years and 11 months who presented with oral ulcers, cutaneous lesions, and uveitis. Whole-exome sequencing (WES) detected a mosaic, pathogenic nonsense variant (p.Arg157X) in CYBB. This pathogenic variant was present in ~ 60% of peripheral leukocytes in this patient, a percentage sufficient to result in defective production of reactive oxygen species (ROS), but not life-threatening infections, including BCG lymphadenitis following BCG vaccination. This study describes a somatic mosaicism mutation in the CYBB gene that can cause atypical CGD with inflammatory symptoms.