Immunologic Research[JOURNAL]
Sun
200 papers
Emapalumab plus conventional therapy with or without ruxolitinib for pediatric hemophagocytic lymphohistiocytosis: a single center retrospective study.
Liao M, Xiao L, Gu M … +1 more , Yu J
Immunol Res · 2026 Jul · PMID 42397658 · Publisher ↗
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal hyperinflammatory syndrome characterized by an uncontrolled cytokine cascade. Traditional chemotherapy leaves 30% of patients unresponsive, and...
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal hyperinflammatory syndrome characterized by an uncontrolled cytokine cascade. Traditional chemotherapy leaves 30% of patients unresponsive, and its side effects are significant. Precise targeted therapies are highly anticipated. Emapalumab is a monoclonal antibody targeting interferon-γ, while ruxolitinib is a JAK1/2 inhibitor, and their application in HLH treatment is gaining attention. METHODS: We retrospectively collected clinical data from pediatric HLH patients who received emapalumab added to conventional therapy, with or without ruxolitinib, at our hospital between June 1, 2022, and June 1, 2024. Treatment efficacy, safety, improvement in clinical parameters, and causes of death were analyzed. RESULTS: A total of 10 pediatric patients were included: 7 with refractory disease, 2 with relapsed disease, and 1 with newly diagnosed disease. EBV-associated HLH was observed in 6 of the 10 patients. All patients received emapalumab added to conventional therapy, and 7 patients additionally received ruxolitinib. The median follow-up duration was 164 days (range, 19-473 days). Among the 10 patients, 5 achieved remission. The response rates for fever, hypofibrinogenemia, neutropenia, hyperbilirubinemia, and elevated transaminases were 6/6, 5/5, 8/9, 4/7, and 6/10, respectively. Among patients with relapsed/refractory disease, the remission rate was 2/3 with emapalumab plus conventional therapy alone and 2/6 with the further addition of ruxolitinib. In patients with non-EBV-associated HLH, the corresponding remission rates were 1/2 and 2/2, respectively. In patients with EBV-associated HLH, the rates were 1/1 and 1/5, respectively. CONCLUSIONS: In this small-sample retrospective study, emapalumab showed a more pronounced trend toward alleviating fever, hypofibrinogenemia, and neutropenia than toward improving liver function among pediatric HLH patients. Adding ruxolitinib to the combination of emapalumab and conventional therapy did not demonstrate a clear additional clinical benefit, particularly in the EBV-associated HLH and relapsed/refractory subgroups. These findings are constrained by the study design and sample size and necessitate validation in larger, prospective studies.
Immunological spectrum in patients with thymoma: beyond good syndrome.
Sönmez E, Kalkan F, Balaban Y … +4 more , İnan Mİ, Demirel F, Yeşillik S, Kartal Ö
Immunol Res · 2026 Jul · PMID 42390792 · Publisher ↗
Thymoma is associated with various immunological abnormalities, most notably Good syndrome; however, the full spectrum of immune dysfunction in these patients remains unclear. To evaluate the clinical and immunological c...
Thymoma is associated with various immunological abnormalities, most notably Good syndrome; however, the full spectrum of immune dysfunction in these patients remains unclear. To evaluate the clinical and immunological characteristics of patients with thymoma and to identify occult immunodeficiency as well as associated autoimmune, infectious, and allergic conditions. In this retrospective single-center study, 37 adult patients with thymoma who had undergone thymectomy were evaluated at least one year after surgery. Clinical data, autoimmune and allergic comorbidities, infection history, and immunological parameters including immunoglobulin levels and lymphocyte subsets were analyzed. Good syndrome was identified in 2 patients (5.4%). However, additional immunological abnormalities were observed, including NK cell deficiency (16.2%), B cell lymphopenia (5.4%), isolated IgM deficiency (5.4%), and IgG subclass deficiency in 1 patient (2.7%). Recurrent infections were reported in 67.6% of patients. Autoimmune diseases were present in 86% and allergic diseases in 43.2% of patients. Patients with immunological abnormalities tended to have a higher frequency of recurrent infections. Our findings suggest that immune dysfunction in patients with thymoma may extend beyond classical Good syndrome and may involve a broader spectrum of immunological abnormalities. Systematic and long-term immunological evaluation may be important for the early detection and management of these conditions.
Microbiome immune crosstalk in Sjögren's syndrome: mechanistic insights and translational perspectives.
Qi XY, Wang MY, Wei TC … +9 more , Shao FB, Liu SH, Han D, Cheng JW, Zhao YH, Shi L, Luo J, Cheng T, Zhang SX
Immunol Res · 2026 Jul · PMID 42387047 · Publisher ↗
Sjögren's syndrome (SS) is a systemic autoimmune disorder driven by interactions among genetic susceptibility, environmental factors, and alterations in mucosal microbial ecosystems. Emerging evidence from studies of the...
Sjögren's syndrome (SS) is a systemic autoimmune disorder driven by interactions among genetic susceptibility, environmental factors, and alterations in mucosal microbial ecosystems. Emerging evidence from studies of the gut, oral cavity, and ocular surface indicates that microbial dysbiosis is closely associated with SS. Patients frequently exhibit reduced beneficial commensals and expansion of potentially pathogenic taxa, accompanied by epithelial barrier disruption, imbalance of T helper 17 and regulatory T cells, abnormal B-cell responses, and sustained activation of type I interferon signaling. Several mechanisms may contribute to disease development, including molecular mimicry, exosome-mediated immune communication, and alterations in microbiota-derived metabolites. Integrated multi-omics approaches, particularly high-throughput sequencing and metabolomics, have revealed SS-associated microbial signatures and metabolic pathway changes, offering insights for biomarker discovery and therapeutic targeting. Microbiota-directed strategies, such as probiotic supplementation, fecal microbiota transplantation, and investigations of drug-microbiome interactions, have shown potential to restore immune homeostasis. However, current evidence remains limited by small cohort sizes, methodological heterogeneity, and insufficient clarification of causal relationships. This review summarizes microbial alterations in SS, their roles in immune dysregulation, and the therapeutic potential of microbiome-based interventions within the framework of personalized medicine.
Immune checkpoint inhibitor-induced myasthenia gravis and myocarditis: a fatal immune-related adverse event.
Allen WM, Megaly M, Sharma P
Immunol Res · 2026 Jul · PMID 42384108 · Publisher ↗
Checkpoint inhibitors, a class of immunotherapeutic agents, have transformed the oncology landscape by targeting immune checkpoints - regulatory pathways that modulate immune cell activity. By inhibiting proteins such as...
Checkpoint inhibitors, a class of immunotherapeutic agents, have transformed the oncology landscape by targeting immune checkpoints - regulatory pathways that modulate immune cell activity. By inhibiting proteins such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), these agents enhance the immune response against cancer cells. However, their efficacy comes at the cost of a range of immune-related adverse events (irAEs), including autoimmune reactions such as colitis, hepatitis, and endocrinopathies, which can range in severity from mild to life-threatening. We present the case of a 76-year-old man with cholangiocarcinoma on durvalumab, a PD-L1 inhibitor, who presented to the emergency department with shortness of breath, cough, and weakness. Workup led to the diagnosis of immune-related myasthenia gravis and a non-ST-elevation myocardial infarction (NSTEMI), the latter believed to be secondary to durvalumab-induced myocarditis. Initial treatment with intravenous immunoglobulin (IVIG) produced brief, partial symptomatic improvement but failed to resolve respiratory weakness or other bulbar manifestations. His condition deteriorated rapidly, progressing to respiratory failure within weeks of onset. Given the refractory nature of his disease course, he was subsequently treated with a repeat dose of IVIG and prednisone, then transferred to an outside facility for plasma exchange. Despite these interventions, the patient ultimately succumbed to his illness. This case highlights the rare but potentially fatal concurrent occurrence of immune-related myasthenia gravis and myocarditis as irAEs in a patient receiving durvalumab for cholangiocarcinoma. While checkpoint inhibitors have revolutionized outcomes across many solid tumor malignancies, this case underscores the diagnostic and management challenges posed by severe, refractory irAEs, and the importance of early recognition and aggressive treatment in this patient population.
TRIM28 and TRIM32: multifaceted regulators of innate immunity and antiviral defence.
Biju SS, Arya RP, Lahon A
Immunol Res · 2026 Jun · PMID 42377665 · Publisher ↗
As versatile E3 ubiquitin ligases, Tripartite Motif (TRIM) proteins are essential elements of the innate immune response. The antiviral roles of TRIM28 and TRIM32 have been well documented, and they function in different...
As versatile E3 ubiquitin ligases, Tripartite Motif (TRIM) proteins are essential elements of the innate immune response. The antiviral roles of TRIM28 and TRIM32 have been well documented, and they function in different ways. TRIM28 regulates the transcriptional expression of antiviral genes, while TRIM32 ubiquitinates host or viral proteins and directs their proteasomal breakdown. When taken together, they represent complementary transcriptional and post-translational host defence mechanisms. While TRIM28 primarily acts as a transcriptional repressor and TRIM32 as an E3 ubiquitin ligase, both proteins also play opposing roles in cell differentiation and immunity. Given the large number of TRIM family members, focusing on these two allows us to present representative transcriptional and ubiquitination-mediated regulatory mechanisms in depth. This review focuses on the regulatory differences in TRIM28 and TRIM32 in RIG-like receptor (RLR) signalling, Stimulator of Interferon Genes (STING) pathways, Toll-like receptor (TLR) signalling, and NOD-like receptors (NLR)-mediated inflammation, which are key to the host's immune response. These protein interactomes exhibit a significant interaction with other cellular pathways, broadening their significance beyond antiviral responses to encompass broader genetic and therapeutic implications.
Decoding PANoptosis: Crosstalk of cell death pathways in immunity and inflammation.
Subashree K, Harithpriya K, Ganesh GV … +1 more , Ramkumar KM
Immunol Res · 2026 Jun · PMID 42362957 · Publisher ↗
PANoptosis is an emerging regulated cell death that integrates the molecular machinery of apoptosis, necroptosis, and pyroptosis into a combined, highly coordinated process. Defined as a distinct, integrative form of cel...
PANoptosis is an emerging regulated cell death that integrates the molecular machinery of apoptosis, necroptosis, and pyroptosis into a combined, highly coordinated process. Defined as a distinct, integrative form of cell death, PANoptosis simultaneously engages these three pathways through a multiprotein scaffold known as the PANoptosome, ensuring robust elimination of infected, damaged, or transformed cells. Initially described in response to viral infections, PANoptosis is now recognized as a critical regulator of immune defense, inflammation, and tissue homeostasis, with broad implications for infectious diseases, cancer, autoimmune disorders, neurodegeneration, and ischemia-reperfusion injury. This review provides a comprehensive overview of the molecular composition of the PANoptosome, key triggers of PANoptosis, and its morphological and biochemical hallmarks. We further discuss its dual roles as both a protective and pathogenic mechanism, highlighting context-dependent contributions to host defense and disease progression. Finally, we examine therapeutic opportunities, including small-molecule inhibitors and gene-editing approaches, and outline current challenges, such as the identification of reliable biomarkers and the need for precision-targeted strategies. By integrating recent advances, this review highlights PANoptosis as a conceptual shift in cell death biology and a promising avenue for novel interventions in inflammation-driven diseases.
Comment on "Anti-neutrophil cytoplasmic antibodies in interstitial lung disease: results from a cross-sectional study and meta-analysis".
Tahir S, Chaudhary Z, Un Nisa N
Immunol Res · 2026 Jun · PMID 42360652 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association between COVID-19 booster vaccination and influenza mortality: a nationwide retrospective cohort study using the SIVEP-Gripe database in Brazil.
Sardinha DM, Neves NMM, de Nazaré Soares T … +13 more , Silva MJA, de Vasconcelos LA, da Conceição Cruz LR, Takeda KFF, Andrade NCO, do Socorro Dos Santos S, Soares FC, da Luz Dias Júnior NJ, Rodrigues YC, Ferreira IP, do Couto Abreu Pamplona MC, Peixoto IVP, Lima LNGC
Immunol Res · 2026 Jun · PMID 42324378 · Full text
To identify clinical and epidemiological predictors of mortality among patients hospitalized with laboratory-confirmed influenza in Brazil during 2024, and to evaluate the association of vaccination and antiviral therapy...
To identify clinical and epidemiological predictors of mortality among patients hospitalized with laboratory-confirmed influenza in Brazil during 2024, and to evaluate the association of vaccination and antiviral therapy with clinical outcomes. We conducted a nationwide retrospective cohort study using the Brazilian SIVEP-Gripe surveillance database. All hospitalized patients with RT-PCR-confirmed influenza and known outcomes were included. Multivariable logistic regression was initially performed to explore predictors of mortality. To more rigorously assess the association between COVID-19 booster vaccination and mortality, a propensity score-based inverse probability of treatment weighting (IPTW) approach was applied, with weights truncated at 10. E-values were calculated to assess robustness to unmeasured confounding. A total of 15,995 hospitalized influenza cases were included, with an overall case fatality rate of 12.1%. Influenza A predominated (88.0%) and was associated with higher mortality than Influenza B. In IPTW-weighted models, COVID-19 booster vaccination remained independently associated with reduced mortality (OR 0.90, 95% CI 0.84-0.97; p = 0.007). Additional risk factors included dyspnea, respiratory distress, and low oxygen saturation, as well as comorbidities such as obesity, diabetes, liver disease, and immunosuppression. Protective factors included influenza vaccination (OR 0.77) and oseltamivir use (OR 0.81). The model demonstrated good discrimination (AUC = 0.81, 95% CI 0.80-0.82). The E-value for the booster association was 1.46, indicating moderate robustness to unmeasured confounding. Influenza mortality in Brazil is primarily driven by age, comorbidities, and clinical severity at presentation, but is significantly mitigated by vaccination and antiviral therapy. The observed association between COVID-19 booster vaccination and reduced mortality suggests a possible heterologous immune effect, although causality cannot be established. These findings support integrated immunization strategies targeting multiple respiratory pathogens.
Moxibustion combined with anti-PD-1 antibodies improves immunosuppression in septic mice potentially through the PD-1/PD-L1 pathway.
Han Y, Zhang H, Han J … +1 more , Han S
Immunol Res · 2026 Jun · PMID 42307810 · Publisher ↗
This study was to investigate the therapeutic effects of moxibustion (Mox) combined with anti-PD-1 antibody on septic mice and the immune regulatory mechanism based on the PD-1/PD-L1 axis. A CLP-induced sepsis mouse mode...
This study was to investigate the therapeutic effects of moxibustion (Mox) combined with anti-PD-1 antibody on septic mice and the immune regulatory mechanism based on the PD-1/PD-L1 axis. A CLP-induced sepsis mouse model was established and intervened with moxibustion and/or anti-PD-1 antibody. It was found that both Mox and anti-PD-1 monotherapy improved mouse survival rates, reduced murine sepsis score, alleviated pathological damage in the liver, lungs, and spleen, mitigated serum biochemical abnormalities, and regulated systemic and local organ inflammation. Combination therapy demonstrated synergistic enhancement effects, yielding the most significant improvements across all metrics. Combination therapy effectively reduced intraperitoneal bacterial load and enhanced macrophage recruitment, reversed sepsis-induced decreases in spleen T cell (CD3⁺, CD4⁺, CD8⁺) proportions and CD3⁺ T cell apoptosis, corrected Th1/Th2 imbalance, and significantly downregulated PD-1 expression on spleen T cells and PD-L1 expression on neutrophils. Combination therapy suppressed PD-1, PD-L1, and STAT3 expression in the spleen while reducing STAT3 nuclear translocation. Combination therapy effectively alleviates early inflammatory storms and late-stage immunosuppression in sepsis, potentially through regulation of the PD-1/PD-L1/STAT3 signaling pathway.
Translating the proBDNF-Notch1 axis in ARDS: from macrophage polarization to globally usable neuroimmune phenotyping.
Vijayasimha M, Srikanth M, Rangwala A
Immunol Res · 2026 Jun · PMID 42301598 · Publisher ↗
Abstract loading — click title to view on PubMed.
Machine learning-based identification of basement membrane-related signature to predict recurrence and immunotherapy benefit in bladder cancer.
Weng M, Wang X, Zhan Y … +5 more , Guo Y, Yan Z, Qu L, Liu Y, Chen C
Immunol Res · 2026 Jun · PMID 42295562 · Publisher ↗
The basement membrane (BM) plays a critical role in regulating bladder cancer (BC) progression. However, a BM-related signature for predicting BC recurrence has yet to be established. In this study, we developed a baseme...
The basement membrane (BM) plays a critical role in regulating bladder cancer (BC) progression. However, a BM-related signature for predicting BC recurrence has yet to be established. In this study, we developed a basement membrane-related signature (BRS) with 7 mRNAs using multiple machine learning algorithms based on data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The predictive performance of BRS for BC recurrence was evaluated via Kaplan-Meier survival and receiver operating characteristic (ROC) curves. A nomogram integrating BRS with clinical characteristics was developed and demonstrated superior clinical utility compared to individual parameters. Notably, immune infiltration analysis revealed distinct microenvironmental phenotypes between the two BRS groups: the low-BRS group was characterized by higher CD8 T cell infiltration and reduced M0/M2 macrophages, indicating an immune-active microenvironment, whereas the high-BRS group exhibited lower CD8 T cell infiltration and enrichment of M0/M2 macrophages, consistent with an immunosuppressive phenotype. Accordingly, the low-BRS group showed a more favorable predicted response to immunotherapy. Experimental data revealed that the upregulation of HIGD2A, one of the BRS gene, significantly suppressed BC cell proliferation, migration and invasion. It also downregulated MMP9 expression, suggesting a potential role in maintaining BM integrity. In conclusion, BRS serves as a novel and effective predictive tool for BC recurrence, and therapeutic targeting of HIGD2A may offer a viable strategy to mitigate the risk of disease progression.Clinical trial registration: Not applicable.
IL-6R-CD3-engineered regulatory T cells alleviate neuropathic pain by remodeling the neuroimmune microenvironment.
Lu C, He P, Wu S … +3 more , Liao X, Xu T, Wang W
Immunol Res · 2026 Jun · PMID 42295497 · Publisher ↗
Chronic neurological condition Neuropathic pain is marked by sustained neuronal sensitization. Regulatory T cells are crucial for preserving immune homeostasis. however, their stability and suppressive activity are often...
Chronic neurological condition Neuropathic pain is marked by sustained neuronal sensitization. Regulatory T cells are crucial for preserving immune homeostasis. however, their stability and suppressive activity are often compromised within inflammatory environments generated after nerve injury, limiting their ability to restrain neuroinflammation. This study sought to determine whether genetically modified regulatory T cells expressing an interleukin-6 receptor-CD3ζ fusion receptor could enhance Treg persistence, functional capacity, and therapeutic benefit in a rat chronic constriction injury (CCI) model. CD4⁺CD25⁺ regulatory T cells were isolated from rat spleens and then transduced with a lentiviral vector expressing IL-6R-CD3ζ-IRES-GFP. The modified cells were subsequently evaluated in vitro for their proliferative capacity, susceptibility to apoptosis, and migratory behavior under inflammatory cytokine stimulation. To establish neuropathic pain, a chronic constriction injury model was generated by placing four loose chromic gut ligatures around the sciatic nerve at approximately 1-mm intervals proximal to the trifurcation. The animals then underwent adoptive transfer of either conventional regulatory T cells or IL-6R-CD3ζ-engineered regulatory T cells. Mechanical hypersensitivity was measured by behavioral testing, whereas flow cytometry together with molecular assays was applied to assess immune cell infiltration, the expression of inflammatory mediators, and the activation of intracellular signaling pathways in spinal cord tissue. Native Tregs did not effectively suppress CCI-associated neuroinflammation. Depletion of these cells exacerbated mechanical hypersensitivity, while adoptive transfer of unmodified Tregs conferred only limited analgesic effects. By contrast, IL-6R-CD3ζ-engineered Tregs retained cytokine-responsive migratory ability, displayed greater proliferative activity, and persisted longer in vivo. Transfer of the engineered Tregs significantly increased paw withdrawal thresholds and alleviated neuropathic pain. Mechanistically, this treatment reduced macrophage infiltration and shifted macrophages toward a less proinflammatory phenotype. It also markedly inhibited microglial activation and inflammatory mediator production, together with suppression of nuclear factor kappa B and mitogen-activated protein kinase signaling. In addition, neutrophil recruitment and effector functions were significantly reduced, including diminished secretion of IL-1β, TNF, IL-6, and matrix metalloproteinases as well as decreased oxidative stress. IL-6R-CD3 engineered Tregs remodel the neuroimmune after nerve injury by regulating macrophage, microglial, and neutrophil responses.
ProBDNF promotes LPS-induced pro-inflammatory polarization of alveolar macrophages via the Notch1 signaling pathway.
Gao Y, Wang N, Xiao Z
Immunol Res · 2026 Jun · PMID 42250171 · Publisher ↗
Macrophage polarization is involved in the pathogenesis of acute respiratory distress syndrome (ARDS). However, the upstream regulators that shape macrophage inflammatory phenotypes under pathological conditions remain p...
Macrophage polarization is involved in the pathogenesis of acute respiratory distress syndrome (ARDS). However, the upstream regulators that shape macrophage inflammatory phenotypes under pathological conditions remain poorly understood. Pro-brain-derived neurotrophic factor (proBDNF) has recently been implicated in immune regulation, but its role in macrophage polarization and the underlying mechanisms are still unclear. Lipopolysaccharide (LPS) stimulation of NR8383 alveolar macrophages was used to model inflammation in vitro. ProBDNF expression was manipulated via adenoviral overexpression or knockdown. Polarization-related gene expression was measured by RT-qPCR, cytokine secretion was assessed by ELISA, and protein levels were examined by Western blotting and immunofluorescence. Neurotrophin receptor expression, including Ngfr/p75NTR and Ntrk2/TrkB, was also evaluated by RT-qPCR. Notch1 pathway activation was assessed by examining NICD levels and the expression of its downstream targets, Hes1 and Hes5. To further assess pathway involvement, NICD knockdown experiments were performed. LPS stimulation significantly increased proBDNF expression in NR8383 cells. Overexpression of proBDNF promoted a shift toward a pro-inflammatory (M1) phenotype, as indicated by increased expression of Cxcl9 and Nos2 and reduced expression of M2 markers (Arg1 and Mrc1). In contrast, proBDNF knockdown produced the opposite effect. Consistently, proBDNF overexpression increased TNF-α secretion and reduced IL-10 production, whereas proBDNF knockdown produced the opposite trend. NR8383 cells expressed Ngfr/p75NTR and Ntrk2/TrkB, with Ngfr showing a more inflammation-responsive pattern. These changes were accompanied by corresponding alterations in Notch1 signaling activity, reflected by changes in NICD, Hes1, and Hes5 expression. Importantly, silencing NICD markedly attenuated the pro-inflammatory polarization induced by proBDNF overexpression. In contrast, inhibition of Notch1 signaling did not affect proBDNF expression, supporting the interpretation that Notch1 functions downstream of proBDNF in this model. ProBDNF promotes macrophage polarization toward pro-inflammatory phenotypes under LPS stimulation, at least in part via Notch1 pathway activation. These findings identify a proBDNF-Notch1 regulatory axis in macrophage-driven inflammation and offer new insight into neuroimmune mechanisms underlying inflammatory lung injury.
EGR1 regulates degranulation and mediator release in C48/80-induced pseudo-allergic reactions.
Sun Y, Li H, Li J … +5 more , Wang Y, Long T, Cui Z, Zhang Y, Liu Z
Immunol Res · 2026 May · PMID 42217066 · Publisher ↗
Allergic diseases significantly impair human health and quality of life, and IgE-independent pseudo-allergic reactions represent a common yet incompletely understood subtype with limited diagnostic and therapeutic option...
Allergic diseases significantly impair human health and quality of life, and IgE-independent pseudo-allergic reactions represent a common yet incompletely understood subtype with limited diagnostic and therapeutic options. Cationic secretagogues such as compound 48/80 (C48/80) can trigger mast-cell degranulation in IgE-independent pseudo-allergic responses, but the downstream transcriptional mechanisms remain largely unclear. In this study, we employed a C48/80-induced IgE-independent pseudo-allergic reaction model, combined with transcriptome sequencing, cellular functional assays, and pharmacological interventions, to investigate the role of the transcription factor early growth response 1 (EGR1). Transcriptomic analysis revealed significant upregulation of EGR1 during pseudo-allergic reactions. Functional assays showed that C48/80 stimulation induced characteristic degranulation morphology in RBL-2H3 cells, accompanied by increased beta-hexosaminidase and histamine release. Genetic knockdown of EGR1 or pharmacological inhibition with ML264 markedly suppressed degranulation, was associated with reduced phosphorylation of Lyn, Syk, ERK1/2, and AKT in C48/80-stimulated RBL-2H3 cells, and alleviated tissue edema and inflammatory cell infiltration in a C48/80-induced murine cutaneous vascular permeability/swelling model. Collectively, these findings identify EGR1 as an important regulator of C48/80-responsive pseudo-allergic phenotypes in the RBL-2H3 cell model and mouse models and provide a basis for further mechanistic and translational validation.
Crosstalk between the monocytes and coagulation factor VⅡa aggravates the inflammation in patients with CAD.
Wang B, Han W, Xiu S … +4 more , Li Y, Han X, Zhao M, Wang X
Immunol Res · 2026 May · PMID 42128959 · Publisher ↗
The underlying proinflammatory mechanism of coagulation factor VⅡ in coronary artery disease (CAD) remains unclear. According to the inclusion criteria, 24 non-CAD subjects and 24 patients with CAD were enrolled. The exp...
The underlying proinflammatory mechanism of coagulation factor VⅡ in coronary artery disease (CAD) remains unclear. According to the inclusion criteria, 24 non-CAD subjects and 24 patients with CAD were enrolled. The expression levels of pro-inflammatory (CD14CD86, CD14CD163), anti-inflammatory monocytes (CD14CD163), CD14CD142 and CD14PAR2 monocytes in peripheral blood were detected by flow cytometry. The levels of TNF-α, IL-1β, IL-6, IL-10, and FVⅡ in plasma were determined by ELISA. In vitro experiments were conducted to induce inflammatory THP-1 by FVⅡa. The FVⅡa/TF complex inhibitor PCI-27,483 and PAR2 antagonist AZ3451 were used to clarify the mechanisms. Compared with the control group, the percentage of CD14CD86 pro-inflammatory monocytes were significantly increased in the CAD group, and further elevated after PCI. The results of the levels of CD14CD142 and CD14PAR2 monocytes showed the same trends with CD14CD86 pro-inflammatory monocytes. The levels of CD14CD163 anti-inflammatory monocytes and IL-10 were decreased in CAD patients, but increased after PCI. The pro-inflammatory factors and FVⅡ were significantly elevated in the CAD group and significantly decreased after PCI. Correlation analysis revealed that FVⅡ, TF, and PAR2 were significantly associated with CD14CD86 pro-inflammatory monocytes, and inflammatory factors. In vitro studies further confirmed that the FVⅡa/TF coagulation complex and PAR2 could activate NF-κB in monocytes and aggravate inflammation. Our findings suggest that crosstalk between monocytes and the coagulation complex might contribute to residual inflammation in CAD, potentially involving the FVIIa/TF/PAR2-NF-κB signaling pathway. Based on these observations, we hypothesize that blocking the interaction between clotting factors and monocytes could represent a promising therapeutic strategy to mitigate residual inflammation, but further rigorous experiments are needed for verification.
Anti-neutrophil cytoplasmic antibodies in interstitial lung disease: results from a cross-sectional study and meta-analysis.
Du D, Wang F, Zhu M … +9 more , Zhang Y, Zhang G, Xie Q, Yin G, Yu J, Lv X, Jiang L, Tang X, Luo F
Immunol Res · 2026 May · PMID 42118447 · Publisher ↗
This study aims to investigate the prevalence, clinical characteristics, and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) across different subtypes of interstitial lung disease (ILD), specific...
This study aims to investigate the prevalence, clinical characteristics, and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) across different subtypes of interstitial lung disease (ILD), specifically idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD) without ANCA-associated vasculitis (AAV), and AAV-ILD. A cross-sectional study was conducted to evaluate the positivity rate and clinical characteristics of ANCA in ILD. In the following meta-analysis, PubMed, Web of Science and Scopus were searched for eligible studies reporting positivity rate of ANCA in ILD. The pooled positivity rates of ANCA, MPO and PR3 in ILD were calculated, and survival outcome between ANCA-positive and ANCA-negative ILD patients were compared. Sensitivity analyses, subgroup analyses and meta-regression was also conducted. A total of 217 ILD patients were enrolled in this cross-sectional study, with an ANCA positivity rate of 7%. In the meta-analysis, with 24 studies and 4,424 patients, the pooled positivity rate of ANCA in IPF, CTD-ILD without AAV, and AAV-ILD were 9%, 15% and 97%, respectively. In patients with IPF, patients with ANCA positivity were more likely to develop honeycombing (OR 2.70, 95%CI 1.09, 6.70, p = 0.03). No significant difference was observed in survival time between IPF patients with or without ANCA positivity (HR 1.18, 95%CI 0.73, 1.90). The positivity rate of ANCA varies significantly across different subtypes of ILD. Future research should focus on the characteristics and prognostic value of ANCA positivity in other ILD subtypes.
Fine specificity of antibodies to SARS-CoV-2 nucleoprotein in patients with COVID-19.
Porciani C, Pisani F, Manca ML … +6 more , Pacini L, Errante F, Mozzo R, De Simone L, Migliorini P, Pratesi F
Immunol Res · 2026 May · PMID 42096144 · Publisher ↗
The production of antibodies against viral structural proteins such as the spike (S) and the nucleocapsid (N) is a hallmark of SARS-CoV-2 infection. The N protein contains several immunogenic regions. In this work we ana...
The production of antibodies against viral structural proteins such as the spike (S) and the nucleocapsid (N) is a hallmark of SARS-CoV-2 infection. The N protein contains several immunogenic regions. In this work we analysed epitope specificity and avidity of anti-N antibodies in COVID-19 patients. Eighty-nine COVID-19 patients were recruited. IgG, IgA, IgM antibodies to recombinant N protein and to 6 different peptides containing predicted B epitopes were measured by ELISA. Antibody avidity was evaluated by chaotropic ELISA. Anti-N IgG, IgA, and IgM were detected in 59%, 41% and 30% respectively; in 11% cases anti-N IgG are the only antibodies present in COVID patients. IgG and IgA anti-N antibodies levels correlate with levels of IL-6 and inversely with PaO/FiO ratio (p < 0,005). Anti-N IgG displayed medium avidity in 51% and high avidity in 49% COVID patients; anti-N avidity was negatively correlated with PaO/FiO (p < 0,05). Median anti-N antibody levels were similar in discharged or deceased patients and antibody avidity was not correlated with outcome. Among peptides, N is the most frequently recognized by IgG, IgA and IgM antibodies followed by N, bound by patients IgG and IgA but anti-N IgG display higher avidity than anti-N IgG. These results indicate that anti-N antibodies are characterized by medium-high avidity and preferentially bind the COOH-terminus of the nucleoprotein. Anti-N antibodies, especially directed towards specific epitopes, might be relevant for the course of the infection, and their induction might improve current vaccination strategies.
Effectiveness and safety of efgartigimod in myasthenia gravis: A meta-analysis of different antibody subtypes.
Sabet H, AbuHamdia A, Zanaty MA … +11 more , El-Moslemani M, Ewis DK, Elyamany Z, Khatatbeh A, Almarfadi A, Al-Rayess H, Altalab G, Aldehri M, Al-Fawzan FF, Shaban EA, Abbas A
Immunol Res · 2026 May · PMID 42096038 · Publisher ↗
OBJECTIVE: To assess the effectiveness and safety of intravenous efgartigimod in patients with myasthenia gravis (MG) and to compare treatment responses between anti-acetylcholine receptor antibody (AChR-Ab)-positive and...
OBJECTIVE: To assess the effectiveness and safety of intravenous efgartigimod in patients with myasthenia gravis (MG) and to compare treatment responses between anti-acetylcholine receptor antibody (AChR-Ab)-positive and -negative subtypes. METHODS: A comprehensive search was conducted in the PubMed, Scopus, Web of Science, and Cochrane CENTRAL databases up to 15 October 2025. Clinical trials and cohort studies evaluating the effectiveness and safety of efgartigimod in patients with MG were included. A random-effects model was used to pool mean differences (MDs) for continuous outcomes and proportions for categorical outcomes, with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed based on study design and MG subtype. RESULTS: Twenty-nine studies (1594 patients) were included. Overall, 83% of patients achieved clinically meaningful improvement (CMI; ≥ 2-point reduction in MG Activities of Daily Living [MG-ADL] score), and 36% achieved minimal symptom expression (MSE; MG-ADL score of 0 or 1) with no significant difference between AChR-Ab-positive and AChR-Ab-negative subtypes. MG-ADL score significantly decreased from baseline (MD: -4.3 points, 95% CI: -4.99 to -3.61), with no difference between the MG subtypes. Quantitative MG score (QMG; MD: -3.6 points, 95% CI: -4.28 to -2.91), MG Quality of Life 15-item revised scale (MG-QoL15r), IgG levels, and corticosteroid use showed significant reductions in the AChR-Ab-positive subtype; however, these outcomes were not reported in the AChR-Ab-negative subtype. Serious adverse events were reported in 4.42% of patients. CONCLUSION: Efgartigimod significantly improved clinical symptoms and quality of life in patients with MG and may offer a steroid-sparing effect, with no significant differences observed between subtypes.
An integrated AI-driven vaccine design process: a systematic review of workflows from generative design to translational prediction.
Shafaati M, Nikzadjamnani F, Ghorbani M
Immunol Res · 2026 May · PMID 42095951 · Publisher ↗
Traditional vaccine development faced significant hurdles, including lengthy timelines and high costs, which hindered rapid responses to pathogens. Although the emergence of AI offered transformative potential, the neces...
Traditional vaccine development faced significant hurdles, including lengthy timelines and high costs, which hindered rapid responses to pathogens. Although the emergence of AI offered transformative potential, the necessity for a fully integrated workflow was often overlooked in studies focusing on individual tools. This review addressed a critical gap by synthesizing AI technologies across the vaccine design process, focusing on the integrated workflow from antigen discovery to clinical translation. A systematic framework was required to connect disparate tools and ensure seamless transitions. Consequently, this study provided a comprehensive roadmap for pandemic preparedness and vaccine discovery. A systematic analysis based on the PRISMA framework (2015-2024) was conducted, and 19 landmark articles were reviewed.It was demonstrated that the paradigm shift from predictive to generative AI offered unprecedented opportunities for developing novel antigens and adjuvants with superior immunogenicity. Synthesis of the literature revealed rapid progress toward sophisticated deep learning. Transformer models and Protein Language Models emerged as dominant for epitope prediction, while AlphaFold2 became the standard for structural modeling. The advent of generative AI for de novo antigen design represented the leading edge of the discipline. Additionally, AI-enhanced molecular dynamics and digital twin simulations accelerated clinical validation and manufacturing scalability. The "Integrated AI Workflow for Vaccine Design and Development" was emphasized as a comprehensive system and a prerequisite for sustainable innovation. Overall, this analysis served as a strategic roadmap for utilizing AI as a transformative framework for next-generation vaccine discovery and pandemic preparedness.
Natural history and long-term outcomes of kawasaki disease following spontaneous defervescence: 31 years of experience from North India.
Pilania RK, Barman P, Cv G … +10 more , Sharma Y, Thakur V, Dhaliwal M, Sharma S, Vignesh P, Suri D, Naganur SH, Singhal M, Rawat A, Singh S
Immunol Res · 2026 May · PMID 42089918 · Publisher ↗
Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who deferve...
Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who defervesce spontaneously are not clear. In this study, we analysed patients with KD diagnosed between 1994 and 2024 at our centre who had defervesced spontaneously, had normal acute-phase reactants, and underwent echocardiographic examination, and in whom IVIg had not been administered. We reviewed the records of patients with KD from January 1994 - December 2024. The diagnosis of KD was based on standard guidelines. Patients with KD were said to be in spontaneous defervescence when they remained afebrile for ≥ 48 h, had normal acute-phase reactants [C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR)] and no coronary artery abnormalities (CAAs) on echocardiography at presentation, and when IVIg was not administered. Patients with spontaneous defervescence were subdivided into (i) early defervescence (Ed-KD), if the interval between onset of symptoms and defervescence was < 10 days, and (ii) late defervescence (Ld-KD), if the duration between onset of symptoms and defervescence was ≥ 10 days, respectively. Details of the clinical profile, laboratory investigations, and echocardiography findings were obtained from the records. Of the 1499 patients with KD enrolled during the study period, 115 patients (7.7%; 86 boys) defervesced spontaneously. The median age at disease onset was 6 years (mean, 5.6 years; range, 0.8-15 years). The median duration of fever, defined as the total duration of the febrile episode before spontaneous defervescence, was 5 days (range, 1-21 days). The median interval between illness onset (defined as fever onset) and diagnosis of KD was 15 days (range, 4-40 days), indicating that diagnosis was often made after fever had already subsided. The most common clinical feature was periungual desquamation, followed by rash, oral-mucosal changes, cervical lymphadenopathy, and conjunctival injection. Incomplete presentation was noted in 73.9% (n = 85/115) of patients. No patient has developed CAAs or other cardiac sequelae over a median follow-up of 9 months (range 2 months-156 months). The cumulative follow-up for the cohort was 235 patient-years. The 'low-risk' subgroup of patients with KD who defervesce spontaneously, and have normal acute phase reactants with no CAAs at presentation, have good clinical and coronary outcomes.
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