Immunologic Research[JOURNAL]
Sun
200 papers
Hypermethylation of lysosomal-associated genes LAMP1 and LAMP2 compromises lysosome function in patients with acute lymphoblastic leukemia.
Refaai R, Fouda S, Hefni DM … +5 more , Ragab D, Elshamy AM, Shoaib H, Guirgis AA, Khalil H
Immunol Res · 2025 Nov · PMID 41254398 · Full text
DNA methylation plays a pivotal role in the pathogenesis of Acute Lymphocytic Leukemia (ALL), a hematological malignancy marked by abnormal cellular behavior and immune dysregulation. This study aimed to investigate how...
DNA methylation plays a pivotal role in the pathogenesis of Acute Lymphocytic Leukemia (ALL), a hematological malignancy marked by abnormal cellular behavior and immune dysregulation. This study aimed to investigate how alterations in DNA methylation affect lysosmal function in pediatric ALL. A total of 50 blood samples were collected from children diagnosed with ALL and analyzed for biochemical markers associated with the disease. Expression levels of key DNA methylation regulators, including DNA methyltransferase 1 (DNMT1) and DNMT3, were evaluated and compared with those from healthy controls. In addition, pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-27 (IL-27), and tumor necrosis factor-alpha (TNF-α), were monitored over a six-day period prior to treatment initiation. The study also assessed the expression of lysosome-associated membrane proteins, LAMP1 and LAMP2, which are essential for lysosomal function and the degradation of autophagosomes. To determine the DNA methylation status of the promoter regions of these genes, genomic DNA underwent sodium bisulfite treatment and digestion with methylation-sensitive and methylation-dependent restriction enzymes, followed by amplification with gene-specific primers. Our results revealed a significant upregulation of DNMT1 and DNMT3 in ALL samples, along with a marked downregulation of TET1 gene expression, which is responsible for DNA demethylation. This suggests that disrupted DNA methylation dynamics may contribute to the pathogenesis of the disease. Furthermore, methylation levels within the CpG islands of the LAMP1 and LAMP2 promoter regions were substantially elevated, showing more than a seven-fold increase in ALL samples compared to healthy control blood samples. In ALL samples, the expression levels of LAMP1 and LAMP2 were significantly reduced, may due to promoter region hypermethylation, which contributes to lysosomal dysfunction. In parallel, the expression of autophagy-related genes such as ATG5 and LC3B, markers of autophagy initiation and maturation, respectively, was markedly increased, suggesting an accumulation of autophagosomes that depend on functional lysosomes for complete degradation. Additionally, elevated levels of pro-inflammatory cytokines IL-6, IL-27, and TNF-α were consistently observed in ALL patients, indicating heightened immune activation that may drive disease progression. Collectively, these findings underscore the pivotal role of DNA methylation in disrupting lysosomal function, leading to autophagosome accumulation and impaired recycling of cytoplasmic components.
MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.
Wu X, Liu L, Zhao R … +1 more , Chen W
Immunol Res · 2025 Nov · PMID 41240162 · Full text
IgA nephropathy is characterized by the deposition of IgA and complement C3 in the glomerular mesangial region. Recent research has pointed out the critical role of mitochondrial damage during the occurrence and developm...
IgA nephropathy is characterized by the deposition of IgA and complement C3 in the glomerular mesangial region. Recent research has pointed out the critical role of mitochondrial damage during the occurrence and development of IgAN. During IgAN progression, elevated myc promotes the transcription of HRD1, which in turn induces the ubiquitination of MFN1, leading to mitochondrial dysfunction. We found that the expression levels of myc and HRD1 were elevated in IgAN. Down-regulation of HRD1 and myc successfully alleviated IgAN progression by promoting cell survival, reducing renal injury and improving mitochondrial homeostasis. Additionally, we observed reduced levels of MFN1 expression in IgAN. Overexpression of MFN1 significantly inhibited IgAN progression, while the deficiency of MFN1 exacerbated IgAN injury. In summary, our findings revealed that myc plays a critical role in regulating mitochondrial function in IgAN by promoting HRD1 transcription and inducing MFN1 ubiquitination. These results suggested that targeting myc/HRD1/MFN1 axis may offer a novel therapeutic strategy to combat IgAN progression.
Deciphering macrophage dynamics and immune evasion strategies by the intracellular bacteria.
Munir F, He B, Shakoor A … +2 more , Liu J, Ma W
Immunol Res · 2025 Nov · PMID 41239125 · Publisher ↗
Macrophages are the constituents of the innate immune system that play an important role in the control of infections, phagocytosis, tissue surveillance, and homeostasis. Macrophages display multiple strategies to cope w...
Macrophages are the constituents of the innate immune system that play an important role in the control of infections, phagocytosis, tissue surveillance, and homeostasis. Macrophages display multiple strategies to cope with the invading microbes and prevent the spread of infections. On the other hand, many intracellular pathogens have evolved strategies to circumvent the macrophage-mediated immune responses and even thrive inside macrophages for their survival and replication. The intracellular bacteria possess a specific secretory system that secretes molecules that help regulate the host's immune responses. For example, Mycobacterium tuberculosis can successfully hide itself from the host immune system and replicate inside the host phagocytic cells with the help of chemicals secreted by its ESX secretion system. Therefore, it is necessary to deeply understand the interactions between macrophages and intracellular bacteria. This review gives insight into the biology of macrophages, inducers of antimicrobial responses in macrophages, and the secretory molecules of pathogens that aid in evading the host immune responses.
Glutaminase as a metabolic checkpoint in NK cell cytotoxicity: mechanistic uncertainties and translational implications.
Yang D, Wang G
Immunol Res · 2025 Nov · PMID 41231355 · Publisher ↗
In their recent study, Jedlička et al. demonstrate that glutaminase (GLS) activity is indispensable for sustaining human natural killer (NK) cell cytotoxicity, positing it as a key metabolic regulator of effector functio...
In their recent study, Jedlička et al. demonstrate that glutaminase (GLS) activity is indispensable for sustaining human natural killer (NK) cell cytotoxicity, positing it as a key metabolic regulator of effector function. While this work provides a valuable foundation for understanding NK cell immunometabolism, our analysis identifies several critical areas requiring deeper exploration. This letter offers a prospective critique, highlighting the incomplete delineation of the downstream metabolic mechanisms-specifically regarding energy production, biosynthetic precursor synthesis, and redox homeostasis-that link GLS activity to the cytolytic machinery. Furthermore, we question the physiological relevance of these in vitro findings within the nutrient-deprived and competitive tumor microenvironment (TME), where NK cells must exhibit metabolic flexibility. A paramount concern is the translational double-edged sword of GLS inhibition, which may inadvertently suppress anti-tumor immunity. We conclude that future research must employ integrated multi-omics and in vivo models to resolve these complexities, which is essential for harnessing NK cell metabolism without compromising its therapeutic potential.
Polymorphisms in STAT4 and PTPRC genes in rheumatoid arthritis: a Brazilian study and meta-analysis of susceptibility and TNFi response.
de Araújo JLF, de Almeida IM, Dos Santos Rodrigues PAS … +10 more , de Sá Garcia Landeiro L, Calmon LC, Cruz JVA, de Moreira ATA, de Oliveira Santos J, Pinheiro GP, da Cruz Filho ÁAS, de Figueiredo CAV, de Moura Santos P, Dos Santos Costa R
Immunol Res · 2025 Nov · PMID 41231349 · Publisher ↗
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Genetic factors play a key role in its pathogenesis and may also influence th...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Genetic factors play a key role in its pathogenesis and may also influence therapeutic response. This study aimed to investigate the association of the STAT4 rs7574865-T and PTPRC rs10919563-A polymorphisms with RA susceptibility and response to TNF inhibitor (TNFi) treatment in a Brazilian population. A case-control study was conducted including 295 RA patients treated with TNFi and 303 healthy controls. Genotyping of rs7574865 (STAT4) and rs10919563 (PTPRC) was performed. Associations with RA susceptibility, TNFi treatment response, and therapy discontinuation due to adverse events were evaluated under different genetic models. A meta-analysis integrating our results with previously published studies was also conducted. The rs7574865-T allele was associated with increased RA risk (OR: 1.43; 95% CI: 1.03-1.99; p = 0.036; p perm = 0.042), reduced response to TNFi (OR: 0.28; 95% CI: 0.07-0.99; p = 0.047; p perm = 0.058), and higher likelihood of treatment discontinuation due to adverse events (OR: 1.89; 95% CI: 1.01-3.58; p = 0.047;p perm = 0.034). After permutation-based correction (1,000 iterations), all associations remained consistent except for the recessive model in TNFi response, which became non-significant (p_perm = 0.058). The meta-analysis confirmed a 40% increased RA susceptibility in T allele carriers. No significant association was observed for rs10919563-A regarding RA risk or TNFi response. A genetic interaction between STAT4 (G/T) and PTPRC (A/A, p = 0.008; G/G, p = 0.017) genotypes was observed, suggesting an increased RA risk for these genotype combinations, without significant correlation with TNFi treatment outcomes. Our findings reinforce the role of STAT4 rs7574865-T in RA susceptibility and TNFi treatment outcomes and highlight the potential for personalized therapeutic strategies based on genetic profiles.
BECN1 activator peptide Tat-beclin 1 promotes ferroptosis via the BECN1-SLC7A11 axis to inhibit NSCLC progression.
Gou J, Ma Y, Wu C … +2 more , Zhang T, Jia T
Immunol Res · 2025 Nov · PMID 41231318 · Publisher ↗
Non-small-cell lung cancer (NSCLC) is associated with high mortality. Beclin 1 (BECN1), an autophagy regulator, and ferroptosis, a lipid peroxidation-driven cell death, are both linked to cancer suppression. This study e...
Non-small-cell lung cancer (NSCLC) is associated with high mortality. Beclin 1 (BECN1), an autophagy regulator, and ferroptosis, a lipid peroxidation-driven cell death, are both linked to cancer suppression. This study examines whether the BECN1 activator peptide, Tat-Beclin 1, induces ferroptosis in NSCLC by targeting solute carrier family 7 member 11 (SLC7A11). BECN1 expression in NSCLC tissues and cells was assessed using RT-qPCR, western blot, and immunohistochemistry. Functional assays included CCK-8 for cell viability, C11-BODIPY for lipid peroxidation, glutathione (GSH) and glutamate release, glutathione peroxidase 4 (GPX4) activity, and western blotting for iron metabolism markers (ferritin heavy chain 1 [FTH1], ferritin light chain [FTL], and transferrin receptor [TFRC]). BECN1-SLC7A11 interactions were examined using co-immunoprecipitation and immunofluorescence. BECN1 was knocked down using small hairpin RNA (shRNA), and its effects on ferroptosis were evaluated. System Xc⁻ activity was assessed in control, Tat-beclin 1, Tat-beclin 1 + shRNA-NC, and Tat-Beclin 1 + shRNA-BECN1 groups. Tumor suppression by Tat-beclin 1, erastin, and their combination was assessed in vivo using xenograft models. BECN1 expression was downregulated in NSCLC tissues and cells. Treating NSCLC cells with Tat-beclin 1 upregulated BECN1 expression and promoted ferroptosis, as evidenced by increased lipid peroxidation and malondialdehyde content, reduced GSH and GPX4 activity, and decreased cell viability, without affecting Fe levels or the expression of iron metabolism-related proteins (FTH1, FTL, and TFRC). Knocking down BECN1 attenuated these effects, confirming its central role. BECN1 interacted with SLC7A11 to inhibit system Xc⁻, an effect abolished by knocking down BECN1. Co-treatment with Tat-beclin 1 and erastin enhanced BECN1-SLC7A11 complex formation, more strongly inhibited system Xc⁻, enhanced lipid peroxidation, inhibited the Nrf2-Keap1 signaling pathway and significantly suppressed tumor growth in vivo. Tat-beclin 1 promotes ferroptosis and tumor suppression in NSCLC by activating BECN1 and inhibiting SLC7A11-mediated system Xc⁻ activity.
Regulatory dynamics of Th17 lymphocytes in oral squamous cell carcinoma: immune modulation and emerging immunotherapies.
Kumar U, Kumari M, Singh G … +1 more , Thakur N
Immunol Res · 2025 Nov · PMID 41217689 · Publisher ↗
With the rapid increase in the severity and mortality of OSCC, the potential for new and effective therapies has increased significantly. Therefore, studying the immunological model of this disease will serve as a basis...
With the rapid increase in the severity and mortality of OSCC, the potential for new and effective therapies has increased significantly. Therefore, studying the immunological model of this disease will serve as a basis for developing new treatment approaches. In OSCC, Th17 cells play a crucial role in controlling the outcome of the disease and modulating the response to treatment. This review focuses on Th17 cells, their differentiation and characterization, and the role these lymphocytes play in the occurrence and recovery of OSCC. The prognosis of OSCC may depend on the profile of immune cells infiltrating the tumor and the cytokines they release, as well as the dynamics of transient expression of genes such as PD-1 (Programmed cell death protein-1). The balance between Treg and Th17 cells is crucial for health; Disruption of this balance can lead to autoimmune diseases and disrupt normal body function. The Treg/Th17 axis plays a role not only in the inflammatory cascade but also in bone resorption. One of the factors that most influences the growth of OSCC tumors is the tumor microenvironment. Made up of cytokines, lymphocytes, macrophages, chemokines, growth factors, and similar substances, this tumor milieu significantly controls the course of disease progression. Lifestyle factors, such as smoking and drinking, significantly impact Th17 cell activity and distribution in OSCC patients, influencing their immune profile and treatment outcomes. This highlights the need for personalized approaches. Through this review, we aim to provide data on the factors that make OSCC so deadly and also provide an immune profile of this disease.
Macrophage migration inhibitory factor (MIF): a Janus-faced cytokine in viral pathogenesis and host defense.
Saadh MJ, Muhammad FA, Shareef A … +9 more , Jyothi SR, Nayak PP, Chauhan AS, Singla S, Khasanjanova F, Sameer HN, Yaseen A, Athab ZH, Adil M
Immunol Res · 2025 Nov · PMID 41207997 · Publisher ↗
Macrophage migration inhibitory factor (MIF) is one of several pivotal cytokines that contribute to orchestrate immune regulation, inflammation, and cell survival, acting as both a mediator of host defense and a factor t...
Macrophage migration inhibitory factor (MIF) is one of several pivotal cytokines that contribute to orchestrate immune regulation, inflammation, and cell survival, acting as both a mediator of host defense and a factor that viruses can exploit. This comprehensive review delineates MIF's multifaceted roles across diverse viral families-including Retroviridae, Herpesviridae, Hepadnaviridae, Orthomyxoviridae, Flaviviridae, Paramyxoviridae, and Picornaviridae-highlighting the mechanisms by which viruses manipulate MIF signaling to promote replication, evade immune responses, and induce tissue damage. Viral strategies often involve upregulating MIF expression or leveraging its receptor pathways, such as CD74, CXCR2, and CXCR4, to enhance viral persistence, disrupt barrier integrity, and skew immune polarization toward pro-viral or immunosuppressive states. Conversely, MIF-driven inflammation can worsen pathogenic processes, including cytokine storms, neuroinvasion, and fibrosis, contributing to disease severity. Notably, pharmacologic inhibition of MIF has shown promise in preclinical models, reducing viral replication and mitigating tissue damage, thereby positioning MIF as one of the compelling targets for host-directed antiviral therapies. Understanding the complex, context-dependent functions of MIF in viral infections provides transformative insights for innovative treatment strategies that aim to disrupt virus-host interactions, control inflammation, and improve clinical outcomes in infectious diseases. Future research exploring MIF's molecular interactions, genetic variations, and therapeutic modulation will be crucial for harnessing its potential for personalized, effective antiviral interventions.
Lactylation-related multigene signature in multiple myeloma: integrated prognostic stratification, immune landscape profiling, and therapeutic guidance.
Zhang W, Ming S, Cheng P … +10 more , Shi D, Li J, Wang B, Fang Y, Li M, Cao W, Wang M, Wang Z, Xiao J, Wei W
Immunol Res · 2025 Nov · PMID 41205015 · Publisher ↗
Multiple myeloma (MM) is an incurable hematologic malignancy with high heterogeneity and poor prognosis. Lactylation, a novel post-translational modification, drives tumor progression and immune dysregulation, yet its pr...
Multiple myeloma (MM) is an incurable hematologic malignancy with high heterogeneity and poor prognosis. Lactylation, a novel post-translational modification, drives tumor progression and immune dysregulation, yet its prognostic value in MM remains uncharacterized. To explore the prognostic value of lactylation-related genes in multiple myeloma, our study aims to construct and validate a lactylation-related multigene signature, which can provide integrated prognostic stratification, immune landscape profiling, and therapeutic guidance for MM patients. This study integrated 1,417 MM patients (859 from the TCGA-MMRF training cohort; 558 from the GSE24080 validation cohort) and 121 normal controls. Differential expression identified lactylation-related genes, and a prognostic model was constructed via LASSO-Cox regression. The model was validated in an independent cohort and we assessed immune infiltration and drug sensitivity. We finally identified four lactylation-associated prognostic genes (SLC19A1, KIF23, TOP2A, and XK) and categorized the patients into high-risk/low-risk groups, which differed in survival rates (P < 0.0001). The model showed robust accuracy (3-year AUC = 0.764) and validation (P = 0.0018). Low-risk patients exhibited enhanced anti-tumor immunity (activated dendritic cells↑, CD8⁺ T cells↑) and heightened sensitivity to bortezomi/venetoclax, etc. We established the lactylation-derived gene signature for MM, providing a clinical tool for risk stratification, immune profiling, and personalized therapy.
STAT6 inhibition stabilizes induced regulatory T cells and enhances their therapeutic potential in inflammatory bowel disease.
Arroyo-Olarte RD, Pérez-Noriega FA, Correa-Pérez MF … +3 more , Mejía-Muñoz A, Terrazas LI, Leon-Cabrera S
Immunol Res · 2025 Nov · PMID 41203944 · Full text
The development and stability of induced regulatory T cells (iTregs) are essential for their immunosuppressive function and therapeutic potential in inflammatory diseases. Although Treg-based immunotherapy offers promise...
The development and stability of induced regulatory T cells (iTregs) are essential for their immunosuppressive function and therapeutic potential in inflammatory diseases. Although Treg-based immunotherapy offers promise for restoring immune tolerance, clinical application is limited by the instability and reduced potency of iTregs. STAT6 signaling has been implicated in destabilizing Foxp3 expression, a key marker of Treg identity. Here, we investigated the impact of pharmacological STAT6 inhibition on iTreg differentiation, stability, and function both in vitro and in vivo. Naïve CD4⁺ T cells were differentiated into iTregs under standard conditions or expanded with IL-2 in the presence of the STAT6 inhibitor AS1517499 (AS-iTregs). STAT6 inhibition enhanced iTreg stability, maintaining high expression of Foxp3, CD25, PD-1, and CTLA-4 for up to 10 days, even in inflammatory conditions. AS-iTregs also showed increased mRNA levels of Foxp3, IL-10, TGF-β, and PD-1, and reduced IL-6, IL-1β, and DNMT1 expression-suggesting improved functional and epigenetic stability. In the DSS colitis model, adoptive transfer of AS-iTregs alleviated disease severity, preserved mucosal architecture, and increased goblet cell numbers. Histopathological analysis showed reduced epithelial damage and inflammation compared to controls. Importantly, AS-iTregs did not promote tumor growth in a colitis-associated cancer model. Furthermore, in vivo administration of AS1517499 during acute colitis enhanced Treg expansion, activation, and suppressive function. These findings establish STAT6 inhibition as a promising approach to boost iTreg stability and efficacy, advancing the potential of Treg-based therapies for inflammatory disorders.
History of cold urticaria research: from systematic studies of the 19th century to modern prospective strategies in clinical practice.
Lisiecka MZ
Immunol Res · 2025 Nov · PMID 41199104 · Publisher ↗
This study aimed to determine the current prospective strategies for diagnosing and treating cold urticaria based on the history of its research since the 19th century. The study analysed relevant scientific sources, and...
This study aimed to determine the current prospective strategies for diagnosing and treating cold urticaria based on the history of its research since the 19th century. The study analysed relevant scientific sources, and the main historical milestones of cold urticaria research were identified. Based on the results, a chronology of scientific events was established that formed the modern understanding of the pathogenesis of cold urticaria and contributed to the development of diagnostic and treatment methods used in contemporary clinical practice. Throughout the 19th century, scientists formulated the concept of cold urticaria as an allergic reaction, identifying a causal relationship between exposure to cold and a patient's skin reaction. They expanded this understanding by describing the symptoms, triggers, and mechanism of development, and establishing the hereditary nature of the disease. The technological capabilities of the 20th century significantly improved the level of research. The results obtained have demonstrated the scientific processes that have become the basis for the introduction of existing approaches to the treatment of cold urticaria and have expanded the potential for the development of fundamentally new therapeutic strategies in this area.
Dexmedetomidine protects against postoperative neurocognitive disorder by mitigating mitochondrial dysfunction through regulating the IP3R-GRP75-VDAC1 complex-mediated calcium transport.
Huo Q, Zhang Y, Guo J … +2 more , Jiang YA, Zhao J
Immunol Res · 2025 Nov · PMID 41196448 · Publisher ↗
Dexmedetomidine (Dex), an α2 adrenergic receptor agonist, has been shown to exert protective effects against postoperative neurocognitive disorder (PND) following anesthesia and surgery. This study aimed to investigate t...
Dexmedetomidine (Dex), an α2 adrenergic receptor agonist, has been shown to exert protective effects against postoperative neurocognitive disorder (PND) following anesthesia and surgery. This study aimed to investigate the underlying mechanisms, with a focus on the inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-chaperone glucose-regulated protein 75 (GRP75) calcium transport protein complex-mediated mitochondrial dysfunction. An in vitro sevoflurane-induced SH-SY5Y cell injury model and an in vivo PND rat model induced by sevoflurane anesthesia plus laparotomy were established, and both models were pretreated with Dex. Subsequent assessment included cell viability, apoptosis, inflammatory cytokines, reactive oxygen species (ROS), mitochondrial calcium ion (Ca), mitochondrial membrane potential (MMP), mitochondrial ultrastructure, and ATP production. Cognitive functions including spatial memory, anxiety-like behavior, and recognition memory were evaluated in rats. The expression levels and interactions among IP3R, GRP75, and VDAC1 were examined to elucidate the mechanisms involved. Sevoflurane exposure reduced cell viability, increased apoptosis and inflammation, and induced mitochondrial impairments including ROS overproduction, Ca overload, loss of MMP, ultrastructural damage, and reduced ATP production. Dex pretreatment effectively alleviated all these cellular injuries. Furthermore, Dex alleviated cognitive deficits in PND rats and mitigated neuronal loss, histological damage, apoptosis, neuroinflammation, and mitochondrial ultrastructural damage in hippocampal tissues. Mechanistically, Dex reversed sevoflurane-induced upregulation of IP3R, GRP75, and VDAC1 and disrupted their enhanced interaction. VDAC1 exhibited the most pronounced changes in response to both sevoflurane injury and Dex treatment. Rescue experiments suggested that VDAC1 overexpression abrogated Dex-mediated mitochondrial protection. Dex alleviates cognitive deficits in PND rats by preserving mitochondrial calcium homeostasis and mitigating mitochondrial dysfunction through regulating the IP3R-GRP75-VDAC1 complex. This study may provide critical insights into the neuroprotective mechanisms of Dex in PND and identify potential therapeutic targets.
Characterization of the neuromuscular manifestations in patients with IgG4-related disease: a systematic review.
Rosenstein RF, Baima JP, Giardini HAM … +2 more , Mendonça LO, Silva GD
Immunol Res · 2025 Nov · PMID 41188651 · Publisher ↗
Immunoglobulin G4-related disease (IgG4-RD) neurological involvement typically presents as pachymeningitis. However, there have been reports of neuromuscular manifestations. To review the involvement of the peripheral ne...
Immunoglobulin G4-related disease (IgG4-RD) neurological involvement typically presents as pachymeningitis. However, there have been reports of neuromuscular manifestations. To review the involvement of the peripheral nerves, neuromuscular junction, and muscles in IgG4-RD, we conducted a systematic review of case reports and case series of patients with IgG4-related disease (IgG4-RD) presenting with neuromuscular manifestations, using the PubMed/MEDLINE, Embase, and Scopus databases. Articles were analyzed for demographic characteristics, neurological presentations, systemic involvement, and investigative findings (laboratory, electrophysiological, and pathological). A total of 38 articles, encompassing 42 cases of neuromuscular manifestations in patients with IgG4-RD, were included. Peripheral nerve involvement was frequently reported (25/42, 60%). The most common clinical presentations were mononeuritis multiplex (48%) and polyneuropathy (20%). Electrodiagnostic studies revealed an axonal pattern in 88% of cases, while nerve biopsies were compatible with vessel and nerve infiltration by IgG4-positive cells in 46% (6/13) of cases. Involvement of the neuromuscular junction was infrequently reported (n = 4), presenting as Lambert-Eaton syndrome (25%) or myasthenia gravis (75%), with all cases being negative for anti-acetylcholine receptor antibodies. Muscle involvement (n = 13) manifested as focal myositis in 53% and a limb-girdle muscle weakness pattern in 47%. Creatine kinase levels were elevated in 53%, and muscle biopsy demonstrated IgG4-positive cell infiltration in all focal myositis cases. Our review suggests that typical neuromuscular manifestations in patients with IgG4-RD include mononeuritis multiplex, polyneuropathy, and focal myopathy. However, comorbid conditions should also be considered as potential contributors to neuromuscular manifestations.
Disease activity and immune disbalance are key drivers of infections in patients with idiopathic inflammatory myopathies: results from the MYOTReCSZ cohort.
Santana-de-Anda K, Torres-Ruiz J, Mejía-Domínguez NR … +7 more , Cornejo-Sarmiento F, Tovar-Méndez V, Alcalá-Carmona B, Reyna-Juárez Y, Ostos-Prado MJ, Juárez-Vega G, Gómez-Martín D
Immunol Res · 2025 Nov · PMID 41186650 · Publisher ↗
Patients with idiopathic inflammatory myopathies (IIM) are at increased risk for infections. Identifying clinical and immunological biomarkers predictive of infection is essential. We included 169 patients from the MYOTR...
Patients with idiopathic inflammatory myopathies (IIM) are at increased risk for infections. Identifying clinical and immunological biomarkers predictive of infection is essential. We included 169 patients from the MYOTReCSZ cohort, all with ≥ 6 months of follow-up. Clinical data and laboratory parameters were collected, including: (1) low-density granulocytes and monocyte subsets, (2) serum cytokines, and (3) neutrophil extracellular trap (NET) quantification. The primary outcome was infection development. Most patients were female (72.78%), with a median age of 42. At least one infection occurred in 46.7% of patients; 55.6% were severe and 32.9% had recurrent infections. Independent predictors of infection included number of immunosuppressants (OR 1.7, P = 0.023), gastrointestinal activity score, cardiovascular damage-VAS, anti-Jo1 positivity (OR 10.0, P = 0.05), heliotrope rash, alopecia, and mycophenolate mofetil use (OR 11.9, P = 0.026). Severe infections were associated with number of immunosuppressants, low albumin, constitutional activity score, gastrointestinal damage-VAS, and TLR4⁺ intermediate monocytes (OR 1.0, P = 0.038). Recurrent infections correlated with lower TLR2⁺ classical monocytes (OR 0.4, P = 0.045), cumulative prednisone dose, global damage-VAS (OR 2.0, P = 0.0004), and anti-PM/Scl75 positivity (OR 3.8, P = 0.006). In conclusion, IIM patients with higher baseline activity and damage scores, specific autoantibodies, and altered innate immune cell phenotypes are more likely to develop infections. These parameters may serve as early biomarkers to stratify infection risk in clinical practice.
Seasonal pattern, global search trend, and public interest in arthritis from 2004 to 2022: an infodemiology study.
Zhu YY, Hu X, Wang XS … +3 more , Li S, Wang P, Pan HF
Immunol Res · 2025 Oct · PMID 41168555 · Publisher ↗
Arthritis is a common condition that causes articular cartilage damage, joint tissue destruction, and ligament involvement, representing one of the leading causes of disability worldwide. This study aimed to analyze long...
Arthritis is a common condition that causes articular cartilage damage, joint tissue destruction, and ligament involvement, representing one of the leading causes of disability worldwide. This study aimed to analyze long-term trends and characterize seasonal patterns in global online information-seeking behavior related to arthritis and its associated terms using Google Trends data. We retrieved monthly relative search volume (RSV) data for the search terms "arthritis", "ankylosing spondylitis (AS)", "gout", "juvenile idiopathic arthritis (JIA)", "osteoarthritis (OA)", "psoriatic arthritis (PsA)", "rheumatoid arthritis (RA)", and "systemic lupus erythematosus (SLE)" from Jan 2004 to Dec 2022. Long-term trends were visualized using time-series plots, and seasonal patterns were assessed using cosinor analysis. Analysis of global RSV from 2004 to 2022 revealed distinct and divergent long-term trends across arthritis-related terms. The general term "arthritis," along with "OA" and "RA," displayed an initial decline until around 2010-2011, followed by a sustained recovery and gradual increase. In contrast, "AS," "gout," and "PsA" exhibited consistent upward trends throughout the period, while "JIA" progressively declined and "SLE" remained stable. More importantly, cosinor analysis confirmed statistically significant seasonal patterns (all P < 0.05) for "arthritis", "JIA", "OA", "PsA", and "RA", with amplitudes ranging from 2.28 to 4.22. These rhythms were characterized by a reproducible peak in late winter to early spring (acrophase: Feb 5-Apr 5) and a trough in late summer to early autumn. Thematic analysis of rising queries highlighted public focus on disease classification, clinical manifestations, and treatment-related information. Global online interest in arthritis, as measured by RSV, demonstrated significant long-term and seasonal patterns. The changes in the public's interest in arthritis-related terms can reflect the public awareness and potential medical needs. Our findings underscore the importance of infodemiology in public health monitoring.
SerpinB9 sustains CIITA to orchestrate MHC-II expression and Th1 differentiation in β-glucan-induced macrophages.
Huang X, Ding J, Hao Y … +6 more , Pan J, Yuan M, Shao F, Xie Y, Zhu Z, Qi C
Immunol Res · 2025 Oct · PMID 41160211 · Publisher ↗
Whole glucan particles (WGP) enhance macrophage immune function, while serine protease inhibitor B9 (SerpinB9)-a molecule known to promote tumor immune escape-has an unclear role in WGP-induced macrophage function. In th...
Whole glucan particles (WGP) enhance macrophage immune function, while serine protease inhibitor B9 (SerpinB9)-a molecule known to promote tumor immune escape-has an unclear role in WGP-induced macrophage function. In this study, we found that SerpinB9 knockout in WGP-induced bone marrow-derived macrophages (BMDMs) significantly downregulated surface MHC-II expression, reduced TNF-α secretion, and impaired their ability to induce Th1 cell differentiation. Transcriptome analysis revealed that CIITA, the core regulator of MHC-II transcription, was markedly downregulated in SerpinB9-knockout BMDMs. Further experiments confirmed that CIITA knockdown decreased BMDM surface MHC-II expression, whereas CIITA overexpression rescued MHC-II expression in SerpinB9-knockout BMDMs and restored their capacity to induce Th1 cell differentiation. In conclusion, this study demonstrates that under WGP induction, SerpinB9 regulates macrophage MHC-II expression and Th1 differentiation-inducing ability by maintaining CIITA expression, providing new insights into macrophage immune regulation mechanisms.
Performance of QuantiFERON tests for detecting latent tuberculosis infections: A Meta-analysis.
Weyesa JB, Legesse M, Gumi B … +4 more , Medhin G, Tolossa K, Zewude A, Ameni G
Immunol Res · 2025 Oct · PMID 41144091 · Publisher ↗
Early detection of latent tuberculosis (TB) is crucial for prevention. However, there is a debate over the effectiveness of QuantiFERON tests versus tuberculin skin tests. This meta-review critically evaluated QuantiFERO...
Early detection of latent tuberculosis (TB) is crucial for prevention. However, there is a debate over the effectiveness of QuantiFERON tests versus tuberculin skin tests. This meta-review critically evaluated QuantiFERON (QFT) tests for latent TB detection. This diagnostic meta-analysis reviewed studies from January 2015 to July 22, 2024, sourced from Medline/PubMed. Rigorous selection and data extraction ensured robust results. Diagnostic test results were organised into 2 × 2 tables, and statistical analysis was performed using Stata versions 14 and 16. Statistical significance was set at p < 0.05. Data from 35 studies with 23,383 participants were analysed. Males represented 46.7% of the sample. QFT tests were positive in 22.5% and negative in 77.5% of cases. The pooled sensitivity was 49% (range: 3% to 92%), indicating a risk of false negatives, and its pooled specificity was 86% (range: 31% to 98%), reflecting good performance in ruling out non-TB cases. Sensitivity was moderate in HIV (60%) and HCWs (55%), low in TB contacts (48%), children (43%), and RA (39%), and lowest in IBD (15%). Specificity was highest in IBD (94%), children (91%), HCWs (84%), RA (82%), TB contacts (80%), and moderate in HIV (74%). The positive predictive value (PPV) was 61% (range: 5% to 97%) and the negative predictive value (NPV) was 72% (range:13% to 98%). PPV was moderate in TB contacts (70%), RA (64%), HCWs (63%), HIV (51%), children (50%), and low in IBD (42%), and NPV was high in children (88%), HIV (84%), IBD (79%), HCWs (73%), RA (72%), and moderate in TB contacts (63%), with substantial heterogeneity across populations. Despite high specificity, the lower sensitivity suggests QFT tests may miss some latent TB infections. The diagnostic odds ratio was 5.73 (SE ± 1), indicating strong yet highly variable performance (I² = 96.2%). This highlighted the need to combine QFT tests with other diagnostics. QFT tests had high specificity and NPV, ensuring reliable negative results. However, lower sensitivity reduces PPV, making positive results less definitive. The results also revealed moderate sensitivity in HIV, lowest in IBD, highest specificity in IBD, lowest in HIV, highlighting heterogeneous performances.
Rubella-associated granuloma in a patient with a compound heterozygous RAG1 defect and review of the literature.
Akarsu A, Sonmez G, Schiefer AI … +9 more , Ozcan HN, Üner M, Esenboga S, Duzova A, Oberndorfer F, Ozen S, Ayvaz M, Özçelik U, Cagdas D
Immunol Res · 2025 Oct · PMID 41139764 · Publisher ↗
Recombination-activating gene (RAG) 1-2 deficiencies have a phenotype spectrum from severe combined to combined immunodeficiency (CID). We presented a comprehensive immunologic/genetic/radiologic/pathological, and virolo...
Recombination-activating gene (RAG) 1-2 deficiencies have a phenotype spectrum from severe combined to combined immunodeficiency (CID). We presented a comprehensive immunologic/genetic/radiologic/pathological, and virologic evaluation results of a patient with granuloma and reviewed the medical literature in 2022-2025 period for rubella virus (RuV)-associated granulomas in inborn errors of immunity (IEI). We evaluated a 17-year-old male patient with a necrotic, ulcerated, and exudative lesion extending over the right foot and leg at the edge of amputation. He had a history of recurrent pneumonia and bronchiectasis. Further evaluation revealed systemic granulomas (skin, spleen) in addition to the extremity lesions and low T- and B-, and naive CD4 + T cell numbers. In addition to a defined heterozygous RAG1 mutation(c.1421 G > A, R474H) detected with NGS PID-panel analysis, Sanger sequencing analysis confirmed patient`s CID diagnosis by revealing another heterozygous mutation(c.1181 G > A, R394Q). Histopathology demonstrated necrotizing granulomas with vasculitis and RT-PCR study from the splenic granulomas revealed RuV. The ulceration and exudative extremity lesions regressed with a scar within two months after the initiation of the anti-TNF therapy. In addition to CID therapy, hematopoietic stem cell transplantation was planned from his HLA-matched sibling donor. RuV-associated granuloma usually develop in the first 12 years and accompany gene defects related to Griscelli disease and familial hemophagocytic lymphohistiocytosis (HLH) in the medical literature. Early, comprehensive diagnostic workup for granuloma could further reveal the RuV's role in granulomatous inflammation in IEI, leading to targeted therapy to improve outcomes. Thorough genetic investigation in the presence of granuloma is crucial.
Saccharin from sweetener to immune orchestrator: Saccharin-induced neutrophil chemotaxis and transmigration via taste receptor signaling.
Salama LA, Al-Rashidi HE
Immunol Res · 2025 Oct · PMID 41129033 · Publisher ↗
The cellular immune response is not only affected by endogenous cytokines or mediators but also affected by exogenous chemical products from food. Human blood leukocytes express members of chemosensory taste receptors su...
The cellular immune response is not only affected by endogenous cytokines or mediators but also affected by exogenous chemical products from food. Human blood leukocytes express members of chemosensory taste receptors such as sweet and umami taste receptors (TAS1Rs) and bitter taste receptors (TAS2Rs). These ectopic taste receptors have been found to sense irritants or bacterial lipopolysaccharides and activate innate immunity. Saccharin, an artificial sweetener, can modulate the cellular immune response via the leukocytic taste receptors. The study aimed to investigate the in vitro effect of saccharin on the function of isolated polymorphonuclear neutrophils (PMNs) in the blood by stimulating sweet taste receptors. Chemotaxis and transmigration assays were measured along with transcriptional profiling of selected neutrophil inflammatory chemokines (CXCL1, CCL2 and CCL26) and chemokine receptors (IL8R and CCR4) following in vitro stimulation by saccharin through siRNA knockdown and RT-qPCR. Saccharin was found to activate chemotaxis in isolated human leukocytes and also to activate PMN migration in a concentration-dependent manner. It was found that siRNA against TAS1R2 or TAS1R3 suppressed PMN migration towards saccharin. On the other hand, no loss of migration occurred in PMN transfected with siRNA against TAS1R1 or in non-siRNA transfected PMNs. Incubation of PMNs with saccharin resulted in a significant upregulation of chemokine and chemokine receptor transcript levels. Our study indicates that saccharin can orchestrate innate immunity by stimulating their cognate taste receptors in the peripheral blood PMNs by signaling chemokines and their receptors.
Serum amyloid A: multifaceted roles in inflammation and cellular interactions.
Cheng S, Duan D, Cui H … +5 more , Lian Y, Jiang F, Chen Q, Li T, Zhao L
Immunol Res · 2025 Oct · PMID 41114879 · Publisher ↗
Serum amyloid A (SAA) is a conserved family of acute-phase proteins primarily produced in the liver but also expressed in extrahepatic tissues during inflammation. As a key component of the acute-phase response, SAA exhi...
Serum amyloid A (SAA) is a conserved family of acute-phase proteins primarily produced in the liver but also expressed in extrahepatic tissues during inflammation. As a key component of the acute-phase response, SAA exhibits dynamic upregulation, with serum levels rising up to 1000-fold during inflammation, underscoring its significance in immune modulation and disease pathogenesis. This review provides a comprehensive analysis of SAA's structure, origins, and functions, emphasizing its interactions with immune and non-immune cells. SAA influences cellular processes such as cytokine production, leukocyte migration, and receptor activation, linking it to the pathogenesis of inflammation related diseases. Notably, SAA facilitates chronic inflammation, fibrosis, and therapy resistance while also playing protective roles in infection and tissue repair. The review highlights emerging insights into SAA's dual roles as both a biomarker and a therapeutic target. It underscores critical gaps in understanding SAA's context-dependent effects, receptor interactions, and its regulatory mechanisms in diverse inflammatory settings. These findings point to the necessity of further research to harness SAA's diagnostic and therapeutic potential, particularly in chronic inflammatory and autoimmune diseases. By synthesizing current evidence, this work aims to guide future studies toward advancing clinical interventions targeting SAA-mediated pathways.
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