Immunologic Research[JOURNAL]
Sun
200 papers
Clinical management of autoimmune liver diseases: juncture, opportunities, and challenges ahead.
Chen Y, Chen R, Li H … +1 more , Shuai Z
Immunol Res · 2025 Apr · PMID 40195209 · Full text
The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunologic...
The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunological tolerance, which leads to an inflammatory process that causes liver damage.The self-attack is started by T-helper cell-mediated identification of liver autoantigens and B-cell production of autoantibodies,and it is maintained by a reduction in the number and activity of regulatory T-cells.Infections and environmental factors have been explored as triggering factors for these conditions, in addition to a genetic predisposition.Allelic mutations in the HLA locus have been linked to vulnerability, as have relationships with single nucleotide polymorphisms in non-HLA genes.Despite the advances in the management of these diseases, there is no curative treatment for these disorders, and a significant number of patients eventually progress to an end-stage liver disease requiring liver transplantation.In this line, tailored immune-therapeutics have emerged as possible treatments to control the disease.In addition, early diagnosis and treatment are pivotal for reducing the long-lasting effects of these conditions and their burden on quality of life.Herein we present a review of the etiology, clinical presentation, diagnosis, and challenges on ALDs and the feasible solutions for these complex diseases.
Phenotypic characterization of tumor associated macrophages and circulating monocytes in patients with Urothelial carcinoma of bladder.
Singh A, Raja D, Kaushal S … +3 more , Seth A, Singh P, Sharma A
Immunol Res · 2025 Apr · PMID 40195201 · Publisher ↗
OBJECTIVES: Targeting immune checkpoints has shown clinical efficacy in Urothelial carcinoma of bladder (UBC); however, a substantial percentage of patients remains unresponsive, which warrants the elucidation of novel t...
OBJECTIVES: Targeting immune checkpoints has shown clinical efficacy in Urothelial carcinoma of bladder (UBC); however, a substantial percentage of patients remains unresponsive, which warrants the elucidation of novel therapeutic targets to circumvent immune suppression. Tumor associated macrophages (TAMs) are known for their indispensable role in cancer immunosuppression however, their phenotype and functionality in UBC is not yet clear. MATERIALS AND METHODS: Phenotypic composition and functional markers of TAMs, and circulating monocytes were assessed in surgically resected bladder tumors and PBMC of UBC patients (n = 40). Besides, 40 healthy volunteers were recruited to draw comparisons for peripheral monocytes. Monocytes from patients were treated with autologous bladder tumor conditioned media (TCM) to assess its effects on macrophage-based markers. RESULTS: The infiltration of TAMs was significantly increased in bladder tumor tissue by 21.2% and which displayed both M1 and M2 phenotypic markers, wherein M2 phenotype exhibited positive correlation with disease severity. Circulating monocytes exhibited an increase in frequency of non-classical monocytes by 17.42% and elevated M2-macrophage markers by 20%. Further, TAMs and circulating monocytes exhibits an elevated expression of IL- 10 and inhibitory immune checkpoints (PD-1, PD-L1, and B7-H4). Stimulation of patient-derived monocytes with TCM further augmented the expression of immune checkpoints, and immunosuppressive markers like IL-10, TGF-β and CX3CR- 1. Lastly, M2 phenotype of TAMs and PD-L1+ and B7-H4 + TAMs displayed positive correlation with clinico-pathological parameters in UBC patients. CONCLUSION: This study presents TAMs with an immunosuppressive phenotype that correlates positively with disease severity and suggests TAMs as a potential therapeutic candidate to restore the anti-tumor immunity in UBC.
Pivotal epitopes for islet antigen-specific CD8 T cell detection improve classification of suspected type 1 diabetes with the HLA-A*0201 allele.
Chen Y, Shen M, Gu Y … +21 more , Xu X, Bian L, Yang F, Chen S, Ji L, Liu J, Zhu J, Zhang Z, Fu Q, Cai Y, Chen H, Xu K, Sun M, Zheng X, Shen J, Zhou H, Zhang M, Haskins K, Yu L, Yang T, Shi Y
Immunol Res · 2025 Mar · PMID 40133500 · Publisher ↗
A proportion of patients with new-onset diabetes share similar symptoms with type 1 diabetes (T1D) patients but they are negative for islet antigen-specific autoantibodies. This study was to develop an islet antigen-spec...
A proportion of patients with new-onset diabetes share similar symptoms with type 1 diabetes (T1D) patients but they are negative for islet antigen-specific autoantibodies. This study was to develop an islet antigen-specific CD8 T-cell assay to provide autoimmune evidence regarding these "suspected" T1D patients. HLA-A*0201 individuals with autoAbs T1D, autoAbs suspected T1D, and type 2 diabetes, along with HLA-A*0201 healthy controls were recruited. Using interferon-γ enzyme-linked immunospot assays, the percentages of participants in each group with various islet antigen-specific CD8 T cells were determined. Sixteen out of the 28 islet antigen-specific epitopes tested were T1D specific, meaning that there was a significantly (P < 0.05) greater epitope positivity rate in the autoAbs T1D cohort than in the healthy controls. Using a cutoff value of two positive epitopes, the 16-epitope panel led to a sensitivity of 75.0% and a specificity of 94.4% regarding the autoAbs T1D patients. Even when using an optimized five-epitope panel, the results were highly accurate. Notably, in the application phase of the study, 77.8% of a new cohort of autoAbs suspected T1D patients exhibited positivity when using the five-epitope optimized panel. This highly accurate method, especially for pediatric patients, will improve clinical diagnosis and etiological classification of autoimmune T1D.
α-Amanitin aggravates hepatic injury by activating oxidative stress and mitophagy via peroxiredoxin 6 inhibition.
Cheng Z, Cheng K, Tang Y … +4 more , Duan X, Fu Y, Duan H, Ye Y
Immunol Res · 2025 Mar · PMID 40108092 · Publisher ↗
Mushroom poisoning is mainly caused by α-amanitin (α-AMA), and there is currently no effective drug to treat α-AMA poisoning. Therefore, it is particularly important to find early diagnostic markers for α-AMA injury. Hep...
Mushroom poisoning is mainly caused by α-amanitin (α-AMA), and there is currently no effective drug to treat α-AMA poisoning. Therefore, it is particularly important to find early diagnostic markers for α-AMA injury. Hepatic injury models induced by α-AMA were established both in hepatic cells and mice. The cell viability of human normal hepatic cells after α-AMA treatment was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Liver function parameters was assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). Furthermore, oxidative stress was detected by 2',7'-Dichlorofluorescin Diacetate (DCFH-DA) and Dihydroethidium (DHE) staining. Autophagy- and apoptosis-related proteins were assessed by Western blot and immunofluorescence staining. We applied Hematoxylin and Eosin (H&E), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Oil Red O (ORO) staining to observe the degree of cell damage and hepatocyte apoptosis. In addition, mitochondrial membrane potential was also determined by JC-1 immunofluorescence staining and flow cytometry. The results showed that α-AMA decreased cell viability in a dose-dependent manner. In addition, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and mitochondrial reactive oxygen species (mtROS) were observed to increase in the α-AMA-treated groups, whereas antioxidants superoxide dismutase (SOD) levels were reduced. Moreover, α-AMA promoted hepatocyte mitophagy and apoptosis, which were alleviated by PRDX6 overexpression. Finally, PRDX6 and Parkin were found to accumulate in mitochondria and α-AMA activated mitophagy by silencing PRDX6. Collectively, our results demonstrated that α-AMA activates oxidative stress and mitophagy by inhibiting the expression of PRDX6, leading to hepatic injury. These findings from both in vitro and in vivo models provide insights into the toxicological mechanisms of α-AMA, underscoring the potential of PRDX6 as a therapeutic target for treating α-AMA-induced hepatotoxicity. HIGHLIGHTS: α-AMA leads to ROS accumulation and activates oxidative stress. α-AMA promotes hepatocyte mitophagy and apoptosis. PRDX6 alleviates α-AMA-induced hepatic injury. PRDX6 mediates mitophagy through Parkin.
Utility of simultaneous quantification of TREC/KREC in patients with common variable immunodeficiency phenotype: an observational study from North India.
Barman P, Kaur A, Chawla S … +5 more , Sil A, Dhaliwal M, Rawat A, Singh S, Jindal AK
Immunol Res · 2025 Mar · PMID 40095152 · Publisher ↗
Because of its heterogeneity, common variable immunodeficiency (CVID), the commonest symptomatic inborn error of immunity, is difficult to classify. Limited data suggest T-cell receptor excision circles (TREC) and kappa-...
Because of its heterogeneity, common variable immunodeficiency (CVID), the commonest symptomatic inborn error of immunity, is difficult to classify. Limited data suggest T-cell receptor excision circles (TREC) and kappa-deleting re-combination excision circles (KREC) may be useful to better classify and prognosticate CVID and CVID phenotype. Thirty-four patients with CVID/CVID phenotype and 30 healthy controls were included in this cross-sectional observational study. Simultaneous quantification of TREC/KREC was performed using multiplex real-time polymerase-chain reaction with TaqMan probes. The levels of TREC/KRECs were analyzed for any association with clinical features, immunological investigations, and molecular studies. Median values of KREC and TREC copy numbers in patients with CVID/CVID phenotype were 64.5 and 170 copies/50 ng reaction, respectively, whereas the median values in controls were 79.2 and 190.1 copies/50 ng reaction respectively. We classified the patients into 4 groups based on copy numbers of TREC/KRECs: (A)TREC + /KREC + ; (B) TREC + /KREC-; (C) TREC-/KREC + ; (D)TREC-/KREC- [" + " and " - " denotes TREC/KREC levels above and below median value respectively]. Patients in Group B had higher risk of developing bronchiectasis. There was no significant difference vis-à-vis failure to thrive, infections, autoimmunity and malignancy, and levels of immunoglobulins, CD19 B cells, and CD4:CD8 ratio amongst the 4 groups. Monogenic defects (n = 10/34) were more likely when age of onset was 4 years (p = 0.02), irrespective of TREC/KREC copy numbers. Classification of CVID/CVID phenotype based on TREC/KREC levels may not be feasible; however, a sub-group with low KREC/normal TREC levels may be predisposed to develop bronchiectasis. Patients with younger age of onset (< 4 years) were more likely to have monogenic defects.
Immunoenhancing of the anti-cancer therapy and anti-oxidative stress by co-administration of granulocyte-colony stimulating factor-mobilized stem cells or cells derived from bone marrow and/or spleen plus vaccination with chemotherapeutic cyclophosphamide.
Gomaa S, Nassef M, Tabl G … +1 more , Gabry SE
Immunol Res · 2025 Mar · PMID 40091102 · Publisher ↗
The combination of immunotherapy and chemotherapy, referred to as chemo-immunotherapy, represents a promising regimen for developing new cancer treatments that target the local tumor microenvironment and target tumors in...
The combination of immunotherapy and chemotherapy, referred to as chemo-immunotherapy, represents a promising regimen for developing new cancer treatments that target the local tumor microenvironment and target tumors in their early stages. However, this approach carries potential risks, including myelo- and immunosuppression, as well as the emergence of chemo-resistant tumor cells. The purpose of this study was to investigate how well mobilizing hematopoietic stem cells (HSCs) work when used alongside chemotherapy and immunotherapy to enhance and modulate the immune response, thereby overcoming immunosuppression and eliminating distant cancer cells. Ehrlich ascetic carcinoma (EAC) tumor-bearing mice were intraperitoneal (i.p.) preconditioned with CTX (4 mg/mouse). EAC-bearing mice that were preconditioned with CTX were intravenous (i.v.) administered with adoptive transferred naive mice-derived bone marrow cells (nBMCs) at 5 × 10 through lateral tail vein (nBMCs group), adoptive transferred tumor-bearing mice-derived bone marrow cells (tBMCs) at 5 × 10 cell/mouse (tBMCs group), a combination of adoptive transferred naïve mice-derived bone marrow cells (nBMCs) and naïve mice-derived splenocytes (nSPs) at 5 × 10 (nBMCs/nSPs group), a combination of adoptive transferred tumor-bearing mice-derived bone marrow cells (tBMCs) and tumor-bearing mice derived-splenocytes (tSPs) at 5 × 10 cell/mouse (tBMCs/tSPs group), or G-CSF administrated subcutaneously (s.c.) at 5 µg/mouse (G-CSF group). Subsequently, all mice groups were vaccinated with tumor lysate at a dosage of 100 µg/mouse. Treating EAC tumor-bearing mice with G-CSF, adoptive transferred nBMCs, adoptive transferred tBMCs, adoptive transferred nBMCs/nSPs, adoptive transferred tBMCs/tSPs, resulted in a significantly enhanced anti-tumor effect that was evidenced by increased anti-proliferative activity and growth inhibition against EAC tumor cells, increased necrosis and apoptosis rates among EAC tumor cells, restricted tumor growth in EAC tumor-bearing mice, and reduced levels of carcinoembryonic antigen (CEA) tumor marker. Furthermore, there was an improvement in serum levels of antioxidant enzyme superoxide dismutase (SOD) and malondialdehyde (MDA) in EAC tumor-bearing mice receiving G-CSF, adoptive transferred tBMCs, adoptive transferred nBMCs/nSPs, and adoptive transferred tBMCs/tSPs. Notably, this treatment regimen ameliorates liver and kidney damage associated with CTX administration in EA tumor-bearing mice. The integration of G-CSF-mobilized HSCs, adoptive transferred nBMCs, adoptive transferred tBMCs, adoptive transferred nBMCs/nSPs combination, and adoptive transferred tBMCs/tSPs combination may yield powerful anti-cancer therapy, thereby facilitating more effective anti-tumor immunotherapy strategies when align with anti-tumor responses. This research may propose a novel therapeutic approach that combines chemotherapy and immunotherapy for addressing early-stage cancer. Further research is necessary to connect the biomedical application and heterogeneity of human tumors and immune systems of this regimen to both diagnostic and therapeutic methodologies.
A novel loss of function mutation in the HAVCR2 gene in a patient diagnosed with Hodgkin's lymphoma.
Erdem S, Yilmaz E, Ozcan A … +6 more , Canatan AN, Bisgin A, Dogan ME, Karakukcu M, Unal E, Eken A
Immunol Res · 2025 Mar · PMID 40082338 · Publisher ↗
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Systemic barrier dysfunction in type 2 inflammation diseases: perspective in the skin, airways, and gastrointestinal tract.
Meng J, Xiao H, Xu F … +3 more , She X, Liu C, Canonica GW
Immunol Res · 2025 Mar · PMID 40069459 · Full text
The epithelial barrier in different organs is the first line of defense against environmental insults and allergens, with type 2 immunity serving as a protective function. Genetic factors, and biological and chemical ins...
The epithelial barrier in different organs is the first line of defense against environmental insults and allergens, with type 2 immunity serving as a protective function. Genetic factors, and biological and chemical insults from the surrounding environment altered regulate epithelial homeostasis through disruption of epithelial tight junction proteins or dilated intercellular spaces. Recent studies suggest that epithelial barrier dysfunction contributes to pathologic alteration in diseases with type 2 immune dysregulation including (but not limited to) atopic dermatitis, prurigo nodularis, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. In this review, we summarized current understanding of dysfunction of barrier and its interaction with type 2 inflammation across different organs, and discussed the role of epithelial barrier disruption in the pathogenesis of type 2 inflammation. In addition, recent progresses of emerging barrier restorative therapies are reviewed.
Echinocystic acid ameliorates ischemic acute kidney injury in neonatal rats by attenuating ferroptosis via the Nrf2/GPX4 pathway.
Dang X, Zhang Q, Jiang X … +1 more , Hu X
Immunol Res · 2025 Mar · PMID 40067558 · Publisher ↗
Acute kidney injury (AKI) is the most common complication in neonates with hypoxic-ischemic encephalopathy (HIE), significantly contributing to both morbidity and mortality, and targeting key pathological processes, such...
Acute kidney injury (AKI) is the most common complication in neonates with hypoxic-ischemic encephalopathy (HIE), significantly contributing to both morbidity and mortality, and targeting key pathological processes, such as inflammation, ferroptosis and apoptosis, could be an effective approach to improving survival outcomes in these patients. In this context, echinocystic acid (EA), a pentacyclic triterpene, has shown promising anti-inflammatory, antioxidant, and anti-apoptotic effects in various disease models, suggesting its potential as a therapeutic agent for AKI in HIE. To evaluate the therapeutic potential and underlying mechanisms of EA in ameliorating ischemia/reperfusion (IR)-induced AKI in neonatal rats. Seven-day-old neonatal rat pups were subjected to an IR injury model to induce AKI and treated with EA via intraperitoneal injection. The effects of EA on renal injury were assessed using western blotting, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescence, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) staining. Treatment with EA significantly reduced IR-induced renal pathology and injury scores, as well as serum levels of blood urea nitrogen (BUN) and creatinine (Cr). In addition, EA diminished the release of pro-inflammatory cytokines and reduced the levels of F4/80, a macrophage marker, in the IR-treated pups. EA also attenuated ferroptosis, as evidenced by decreased levels of iron (Fe⁺), reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA), while simultaneously increasing the activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione (GSH). Furthermore, EA reduced apoptosis, as demonstrated by lower levels of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase (PARP). Mechanistically, EA activated the Nrf2/GPX4 pathway, and inhibition of Nrf2 with ML385 reversed EA's beneficial effects on ferroptosis, inflammation, and renal injury. EA may relieve ischemic AKI in neonatal rats by modulating inflammation, ferroptosis and apoptosis, through the activation of the Nrf2/GPX4 pathway, indicating that it could be a promising therapeutic agent for AKI in neonates.
Deciphering autoimmune susceptibility: a meta-analysis of PTPN22 gene variants.
Thomas SM, Veerabathiran R
Immunol Res · 2025 Mar · PMID 40067478 · Publisher ↗
Autoimmune disorders are intricate conditions where the immune system directs its attack towards the body's tissues. The goal is to perform a thorough meta-analysis focusing on the genetic and epigenetic aspects of autoi...
Autoimmune disorders are intricate conditions where the immune system directs its attack towards the body's tissues. The goal is to perform a thorough meta-analysis focusing on the genetic and epigenetic aspects of autoimmune disorders, specifically examining the role of the PTPN22 gene, particularly the rs2476601 variation, in influencing susceptibility to autoimmune diseases. The study followed PRISMA 2020 guidelines and PROSPERO registration and conducted a comprehensive meta-analysis to explore the association between PTPN22 gene variations and autoimmune disorders. Case-control studies presenting genotype information were included, and quantitative data analysis was performed using MetaGenyo software. The meta-analysis included 43 studies with 20,669 controls and 9,397 cases of autoimmune diseases, focusing on the PTPN22 gene rs2476601 polymorphism. Significant associations were observed between the PTPN22 polymorphisms across multiple genetic models, including allelic, dominant, and recessive models. However, no link was found between the over-dominant model. The obtained p-values were < 0.01 for the allele model (C vs T; OR: 0.63, 95% CI: 0.48-0.81, I = 92%), 0.03 for the dominant model (CC + CT vs. TT; OR: 0.47, 95% CI: 0.24-0.95, I = 87%), and < 0.01 for the recessive model (TT vs. CT + CC; OR: 0.61, 95% CI: 0.47-0.79, I = 89%). However, the over-dominant model (CT vs. CC + TT; OR: 1.68, 95% CI: 1.32-2.15, I = 86%) did not show a significant p-value (> 0.05). This meta-analysis emphasizes the significant impact of PTPN22 gene variations on autoimmune diseases, suggesting its potential as a biomarker for assessing risk and guiding targeted interventions.
A comprehensive analysis of scRNA-Seq and RNA-Seq unveils B cell immune suppression in the AAV-loaded brain.
Wu S, Xue L, Li X … +7 more , Wang Y, Zhu Y, Luo Y, Sun J, Jin T, Shu W, Wang Z
Immunol Res · 2025 Mar · PMID 40044925 · Full text
The use of AAV vectors for in vivo gene therapy has demonstrated the potential to permanently correct genetic diseases by delivering functional gene copies to the nuclei of affected tissues. AAV vectors, as tools for in...
The use of AAV vectors for in vivo gene therapy has demonstrated the potential to permanently correct genetic diseases by delivering functional gene copies to the nuclei of affected tissues. AAV vectors, as tools for in vivo gene delivery, are particularly appealing and have shown safety and long-term efficacy in numerous organ-targeted experiments. Nevertheless, employing AAV vectors for gene therapy in the brain faces a notable hurdle in the shape of immune responses, chiefly instigated by the brain's resident immune cells, microglia. Additionally, lower levels of AAV vector-neutralizing antibodies have been detected in the cerebrospinal fluid compared to the circulatory system. This research, leveraging transcriptomic and single-cell RNA sequencing (scRNA-seq) data in conjunction with Mendelian randomization analysis, has identified the potential role of the XBP1 protein in mediating B-cell immunosuppression in the brain via the MDK-NCL ligand-receptor pair and associated genes. Furthermore, it paves the way for further investigation into the regulatory factors and pathways within the immune modulation network, as well as their prospective beneficial implications in immunotherapeutic treatments. By employing various innovative approaches, the study seeks to recreate the immune environment generated by AAV in the brain and preliminarily explore the immune suppression mechanisms induced by AAV vectors in the brain.
Concurrent infections in children with Kawasaki disease: lessons learned over 26 years.
Pilania RK, Basu S, Sil A … +14 more , Mondal S, Thangaraj A, Cv G, Dhaliwal M, Sharma S, Jindal AK, Vignesh P, Verma S, Angrup A, Naganur SH, Singhal M, Rawat A, Suri D, Singh S
Immunol Res · 2025 Feb · PMID 40009125 · Publisher ↗
Etiology of Kawasaki disease (KD) remains an enigma despite more than 50 years of extensive research. There is evidence that concurrent infections may play a role in the pathogenesis of KD. The present study reports vari...
Etiology of Kawasaki disease (KD) remains an enigma despite more than 50 years of extensive research. There is evidence that concurrent infections may play a role in the pathogenesis of KD. The present study reports various infections identified in a large cohort of patients with KD in Northwest India. We reviewed case records of patients with KD from January 1994 to February 2020. Patients with KD identified to have concurrent infection at presentation were analyzed in detail. Of 878 cases of KD during this period, 88 (60 boys, 28 girls; 64 incomplete KD, 24 complete KD) had evidence of concurrent infection. Infective manifestations included superficial and deep-seated abscesses (27.45%), pneumonia (28.4%), gastrointestinal manifestations (29.5%), urinary tract infection (4.5%), and septic arthritis (2.3%). Infectious agents were confirmed in 67/88 patients (76.13%) - these included bacteria (n = 51), viruses (n = 13), fungi (n = 2), and protozoa (n = 1). Among bacteria, infections with Staphylococcus sp. and Streptococcus sp. were the commonest (19/88 and 14/88 patients, respectively). Eighty-one children were treated with intravenous immunoglobulin (IVIg, 2 g/kg) and aspirin. Coronary artery abnormalities (CAAs) were seen in 11/88 patients (12.5%) during the acute phase - these normalized at 6 weeks of follow-up in all patients. To conclude, concurrent infections were seen in 10% of patients with KD at our center. If the clinical presentation suggests KD, one should not exclude the diagnosis even if there is evidence of an accompanying infection. Although 12.5% of patients with infection-associated KD had CAAs, none had persistent CAAs at 6 weeks of follow-up.
Hepatitis C associated mixed cryoglobulinemia glomerulonephritis in the setting of undetectable viral load: successful treatment with hydroxychloroquine and review of the literature.
Shweikeh F, Torres Y, Khan K … +2 more , Mouchli M, Singh I
Immunol Res · 2025 Feb · PMID 39979644 · Publisher ↗
There are an estimated 58 million cases of Hepatitis C (HCV) worldwide. Approximately 38-76% of individuals can develop extrahepatic manifestations such as mixed cryoglobulinemia (MC). Importantly, the appearance of symp...
There are an estimated 58 million cases of Hepatitis C (HCV) worldwide. Approximately 38-76% of individuals can develop extrahepatic manifestations such as mixed cryoglobulinemia (MC). Importantly, the appearance of symptoms due to MC is linked by detectable HCV RNA. A 38-year-old male with remote history of HCV infection diagnosed 8 years prior presented to the emergency department with subacute renal failure with proteinuria, hematuria, and WBC/RBC casts. Biopsy confirmed acute proliferative, non-crescentic, inflammatory glomerulonephritis. He also had new onset cryoglobulinemia. His HCV RNA was low-grade and liver function tests were all within the normal range. A liver biopsy showed signs of chronic hepatitis with mildly active portal fibrosis. The MC was cleared with steroids and a re-measured HCV RNA quantitative was negative. Seven months later, he was readmitted with glomerulonephritis and elevated MC. However, the patient's HCV viral load was undetectable. The patient underwent 6 rounds of plasmapheresis and 6 doses of Rituximab were given with suppression of cryoglobulin to nil. A month later, the MC levels rose again, while the viral load remained undetectable with the possibility of spontaneous remission. After initiation of maintenance hydroxychloroquine, his GFR improved to normal over the next 2 years. Multiple theories have been suggested for the phenomenon including presence of residual virus and lymphoproliferation effects. Hydroxychloroquine could be a successful option, though future studies should corroborate our outcome.
Lithospermic acid targeting heat shock protein 90 attenuates LPS-induced inflammatory response via NF-кB signalling pathway in BV2 microglial cells.
Guo J, Li CG, Mai FY … +6 more , Liang JR, Chen ZH, Luo J, Zhou MC, Wang YL, Yang WT
Immunol Res · 2025 Feb · PMID 39969702 · Full text
Microglia function as a vital constituent in the maintenance of brain homeostasis. Aberrant microglial activation, however, may contribute to neurodegenerative diseases. Lithospermic acid (LA) is a plant-derived polycycl...
Microglia function as a vital constituent in the maintenance of brain homeostasis. Aberrant microglial activation, however, may contribute to neurodegenerative diseases. Lithospermic acid (LA) is a plant-derived polycyclic phenolic carboxylic acid isolated from Salvia miltiorrhiza. The present study investigated the potential effects of lithospermic acid on LPS-induced neuroinflammation in BV2 microglial cells and determined the mechanism of action of this compound. Cells were pre-treated with lithospermic acid for 1 h and incubated with LPS for 24 h. qPCR, immunofluorescence, and immunoblot assays were used to determine the expression of iNOS, COX2, NF-κB p65, and HSP90 expression. ELISA was employed to measure the production of pro-inflammatory cytokines. Lithospermic acid dramatically reduced LPS-stimulated cell migration and decreased NF-κB p65 nuclear translocation. Furthermore, lithospermic acid also markedly decreased the production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in a dose-dependent manner. Additionally, lithospermic acid inhibited NO and PGE2 production in response to LPS, and it also inhibited the expression of iNOS and COX2 in a dose-dependent manner. Molecular docking and experimental verification have demonstrated that lithospermic acid inhibits the activity and expression of HSP90. Small interfering RNA knockdown of HSP90 expression, which abrogated LPS-induced inflammation. These findings suggest that the lithospermic acid targeting HSP90 attenuates LPS-induced inflammatory response via the NF-κB signalling pathway in BV2 microglial cells. Collectively, lithospermic acid may offer therapeutic benefits for neurodegenerative disorders associated with microglial activation and could serve as a potential inhibitor/agent for the treatment of neuroinflammation.
A case of atypical infantile de novo antiphospholipid syndrome presenting with neonatal ischemic stroke without any triggering risk factors as a "second hit" and review of the literature.
Bor D, Bor MV
Immunol Res · 2025 Feb · PMID 39969648 · Full text
Infantile antiphospholipid syndrome (APS) is a rare condition arising from either transplacental transfer of antiphospholipid antibodies (aPL) from the mother or de novo antibody production in the newborn. We present a u...
Infantile antiphospholipid syndrome (APS) is a rare condition arising from either transplacental transfer of antiphospholipid antibodies (aPL) from the mother or de novo antibody production in the newborn. We present a unique case of cerebral artery thrombosis with persistently elevated anti-cardiolipin and anti-β2-glycoprotein-I antibodies, despite the absence of maternal aPL, suggesting primary de novo aPL synthesis. While the prevailing "second-hit" hypothesis suggests that additional thrombotic risk factors are required to trigger APS in infants, our case exhibited no prenatal, maternal, or thrombophilic risk factors. A literature review of 20 reported cases further confirmed that ours was the only case without additional thrombotic triggers among the 18 cases with complete data, challenging the necessity of a "second hit" in neonatal APS. Notably, aPL levels normalized over time without recurrence, raising questions about the need for long-term anticoagulation in select cases, including ours. These findings suggest a potential transient form of infantile APS and highlight the importance of sequential aPL testing to guide treatment. Further research is required to elucidate the mechanisms underlying de novo aPL synthesis and its clinical implications.
Risk factors for predicting medium-giant coronary artery aneurysms in Kawasaki disease.
Zhao L, Wu J, Liu X … +4 more , Zhou K, Hua Y, Shao S, Wang C
Immunol Res · 2025 Feb · PMID 39960616 · Publisher ↗
The objective of this study is to determine whether the data of blood profiles before and after therapy can be useful for predicting medium-giant coronary artery aneurysms (CAA) in patients with KD. In total, 1856 KD chi...
The objective of this study is to determine whether the data of blood profiles before and after therapy can be useful for predicting medium-giant coronary artery aneurysms (CAA) in patients with KD. In total, 1856 KD children from 2013 to 2022 were prospectively recruited. Serial blood samples on the day of initial IVIG infusion and 36-48 h thereafter were collected. The clinical and laboratory parameters were compared between the medium-giant CAA (n = 95) group and the non-CAA group (n = 1761). Multivariate analysis was performed to explore the independent risk factors for medium-giant CAA and the receiver operating characteristic (ROC) curve was used to evaluate and assess the prediction validities. Fever duration prior to initial IVIG infusion, IVIG resistance, cardiac enlargement, white blood cells prior to initial IVIG treatment, albumin levels, and the percentage of △neutrophils were independent risk factors for predicting medium-giant CAA. The predictive value of △neutrophil percentage (≤ 30.2%) demonstrates a relatively high sensitivity (0.84) and a moderate specificity (0.52) for predicting acute medium-giant CAA. The △neutrophil percentage before and 36-48 h after initial IVIG infusion might serve as a promising biomarker in the prediction of medium-giant CAA for KD patients.
PANoptosis-related genes in the prognosis and immune landscape of hepatocellular carcinoma.
Wang X, Qu L, Wen Z … +6 more , Wu Z, Xue Y, Yang X, Yuan Z, Guo Y, Lin X
Immunol Res · 2025 Feb · PMID 39946053 · Full text
In hepatocellular carcinoma (HCC) individuals, the influence of numerous variables on the HCC prognosis has gained widespread recognition. Nevertheless, there remains a need for further elucidation regarding the underlyi...
In hepatocellular carcinoma (HCC) individuals, the influence of numerous variables on the HCC prognosis has gained widespread recognition. Nevertheless, there remains a need for further elucidation regarding the underlying mechanism of PANoptosis-related genes (PRGs) on HCC. A consensus clustering approach, based on the TCGA-LIHC data, was used to identify specific subtypes linked to PANoptosis in this study. Next, a signature consisting of predictive differentially expressed genes for these subtypes was established using a least absolute shrinkage and selection operator (LASSO) regression analysis. Additionally, the reliability of the signature was confirmed through verification investigations using the data from the ICGC database and TCGA-LIHC. In the end, we developed a nomogram to enhance the clinical effectiveness of our prediction tool. PRG signature in this study has been highly related to the prognosis of individuals diagnosed with HCC, which was established with six genes. Also, this signature and clinicopathological features were put together to create a nomogram. Interestingly, the forecasting efficiency of this combination approach is better than other prediction models in the reported literature. In addition, an examination of the immunological surroundings indicates that the group with low risk exhibited elevated ESTIMATE score, ImmuneScores, and StromalScores. More, significant differences in infiltrating immune cells and the expression levels of immune-related genes were found between the two groups. In HCC patients, the PRG signature exhibits potential as a biomarker, offering a significant point of reference for tailoring individual therapy.
Immunization with recombinant HPV16-E7d in fusion with Flagellin as a cancer vaccine: Effect of antigen-adjuvant orientation on the immune response pattern.
Gachpazan M, Alashti AA, Jahantigh HR … +12 more , Moghbeli M, Faezi S, Hosseini SY, Eftekharian MM, Nasimi M, Khiavi FM, Rahimi A, Mianroodi RA, Pakjoo M, Taghizadeh M, Tempesta M, Mahdavi M
Immunol Res · 2025 Feb · PMID 39939497 · Publisher ↗
Human papillomavirus (HPV) is the leading cause of cervical cancer worldwide. The pathogenesis of HPV is mainly dependent on its E7 and E6 proteins. Up to now, different adjuvants have been used to enhance the efficacy o...
Human papillomavirus (HPV) is the leading cause of cervical cancer worldwide. The pathogenesis of HPV is mainly dependent on its E7 and E6 proteins. Up to now, different adjuvants have been used to enhance the efficacy of the immune response against these two proteins. In this study, Flagellin (FLA) was used as adjuvant to test adjuvant activity and also see whether its orientation of attachment can affect the immune response pattern. The E7d-FLA and FLA-E7d in pET28a vector were constructed and then the recombinant proteins were expressed in E. coli BL21 (DE3) bacteria under IPTG induction. The expression of recombinant E7d-FLA and FLA-E7d proteins is confirmed by SDS-PAGE and western blot. Then, recombinant fusion proteins were purified using a nickel-nitrilotriacetic acid (Ni-NTA) column. The recombinant proteins were checked for endotoxin contamination and then quantified by Bradford. Eight-to-ten-week-old male Balb/C mice were immunized subcutaneously with 10 µg recombinant E7d-FLA, FLA-E7d and HPV16E7d vaccine on days 0, 14 and 28. In addition, PBS and FLA groups were considered as control group. Then, spleen cells were harvested to assess lymphocyte proliferation and IFN-γ, IL-4 and IL-17 cytokines. In addition, mice sera were used for specific total IgG and IgG1, IgG2a, IgG2b and IgM antibodies assessment by ELISA. The results show that E7d-FLA is more potent in the induction of lymphocyte proliferation, CTL response and specific total IgG, IgG2a and IgG2b response, while the FLA-E7d vaccine was associated with more IFN-γ, and IL-17 cytokine response. The results of this study proved the ability of FLA as an adjuvant in fusion with E7d in the induction of cellular and humoral immune responses. In addition, it also emphasizes that antigen-adjuvant orientation can affect the immune response strength and polarization against HPV E7d vaccine candidate. HIGHLIGHTS: Flagellin is attached to HPV-16 E7d at the C- or N-terminus to create E7d-FLA and FLA-E7d candidate vaccines. The E7d-FLA vaccine showed a significant increase in lymphocyte proliferation, CTL response and IgG response versus FLA-E7d vaccine. The FLA-E7d vaccine is associated with a significant increase in IFN-γ and IL-17 cytokines response versus E7d-FLA vaccine. It seems that that antigen-adjuvant orientation is an important parameter in the strength and polarization of immune response in HPV E7d vaccine candidate.
Metformin suppresses gammadelta T17 cell differentiation alleviating DSS-induced colitis.
Sun M, Liu H, Ju H … +9 more , Chen H, Yang R, Yan D, Shen L, Cai A, Zhi Y, Xiao L, Tang Q, Wang Y
Immunol Res · 2025 Feb · PMID 39934569 · Full text
Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. Metformin has pleiotropic effects including anti-inflammatory properties and a notable impact on the gut microbiome. γδT17 cells pl...
Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. Metformin has pleiotropic effects including anti-inflammatory properties and a notable impact on the gut microbiome. γδT17 cells play crucial role in initiating and maintaining intestinal inflammation. The effect of metformin on γδT17 cells remains unclear. This study aims to explore the connection between metformin-mediated ameliorated response in colitis mice and γδT17 cell activity. The role of γδT17 cell inhibition in metformin-mediated colitis amelioration was evaluated in mice. The effect of metformin on γδT17 differentiation and the possible mechanism were evaluated in a set of in vitro experiments. Results showed that the accumulation of γδT17 cells was negatively correlated with metformin treatment in DSS-induced colitis mice. Exogenous γδT17 cells blocked metformin-mediated colitis inhibition. Furthermore, metformin inhibited γδT17 differentiation, which was related to the inhibition of mTOR/RORγt activity. Our results reveal that metformin ameliorates colitis symptoms by suppressing γδT17 differentiation, suggesting a viable strategy against UC, although the mechanism of metformin in inhibiting γδT17 differentiation remains to be further studied.
The role of NF-κB pathway and its regulation of inflammatory cytokines in scleral remodeling of form-deprivation mice model.
Xiao K, Chen Z, He S … +2 more , Long Q, Chen Y
Immunol Res · 2025 Feb · PMID 39920470 · Publisher ↗
Myopia has become a worldwide public health problem. In this study, we constructed a form deprivation (FD) myopia mouse model and explored the potential role of NF-κB pathway and inflammatory cytokines in scleral remodel...
Myopia has become a worldwide public health problem. In this study, we constructed a form deprivation (FD) myopia mouse model and explored the potential role of NF-κB pathway and inflammatory cytokines in scleral remodeling during myopia development. Wild-type (WT) mice and C6-knockout (KO) mice were categorized into two groups: FD and normal control (NC). The right eye was covered using a translucent balloon for 4 weeks, and the left eye remained untreated which served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, 4 weeks later under normal visual conditions, and 4 weeks after FD. The mRNA and protein levels of scleral TNF-α, IL-6, IL-1β, MMP-2, collagen I, and p-NF-κB p65 were detected using quantitative PCR and western blot. Under normal visual conditions, no significant difference existed in refraction and axial length between WT and C6 KO mice. After 4 weeks of deprivation, the interocular differences of C6 KO mice were lower than those of WT mice (refraction - 2.41 ± 0.86D vs. - 4.33 ± 0.87D, P = 0.003; axial length 0.044 ± 0.028 mm vs. 0.082 ± 0.026 mm, P = 0.034). Moreover, TNF-α, IL-6, IL-1β, MMP-2, and p-NF-κB p65 levels increased, and collagen I levels decreased in deprived eyes of WT mice. Whereas these trends were weakened in C6 KO mice. Scleral C5b-9 could activate the NF-κB pathway, promoting the expression of inflammatory cytokines and MMP-2 levels, which ultimately affected scleral remodeling.
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