Immunologic Research[JOURNAL]
Sun
200 papers
Atopic dermatitis in inborn errors of immunity: at the interface of immunodeficiency and immune dysregulation.
Szczawińska-Popłonyk A
Immunol Res · 2025 Oct · PMID 41111099 · Full text
Inborn errors of immunity (IEI) encompass a broad spectrum of immunodeficiency disorders characterized by variability in genetic background, individual immunophenotype, and clinical manifestations with organ-specific imm...
Inborn errors of immunity (IEI) encompass a broad spectrum of immunodeficiency disorders characterized by variability in genetic background, individual immunophenotype, and clinical manifestations with organ-specific immunopathology and immune dysregulation in the form of atopy, autoimmunity, polyclonal lymphoproliferation, and malignancy. With the ever-expanding insight in the pathophysiology of IEI, atopy may be perceived as an integral part and even a hallmark of IEI diseases. This review is aimed at gathering, delineating, and summarizing the immunogenetic underpinnings of IEI diseases accompanied by atopic dermatitis. Particular emphasis is laid on syndromes connected with atopy, such as hyper-IgE syndromes, Omenn syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, Netherton syndrome, Wiskott-Aldrich syndrome, and atypical complete DiGeorge syndrome. Therefore, atopic dermatitis proved not to be a sole disease, but rather a warning sign of multiple pediatric monogenic immunodeficiency disorders. Surpassing from the era of clinical and immunological diagnosis to the era of immunogenetics and the integrated "omics" approach highlighted the complex and heterogeneous immunopathology of atopic dermatitis. It also paved the way for patient-tailored immunotherapies with monoclonal antibodies and small molecules targeted at suppressing atopic inflammatory processes and improving disease-associated outcomes.
Associations between female reproductive factors and osteoarthritis in women ≥ 50 years old: An NHANES 1999-2018 analysis of more than 10,000 women.
Cheng LY, Huang KC, Lu YC … +1 more , Chuang PY
Immunol Res · 2025 Oct · PMID 41108481 · Publisher ↗
Osteoarthritis (OA) is the most common form of arthritis, and as the population ages, the incidence and prevalence of OA are projected to rise, particularly affecting women. This study investigates the association betwee...
Osteoarthritis (OA) is the most common form of arthritis, and as the population ages, the incidence and prevalence of OA are projected to rise, particularly affecting women. This study investigates the association between female reproductive factors (age at menarche, menopause, gravidity, parity, and reproductive lifespan) and OA in women ≥ 50 years old using data from the United States National Health and Nutrition Examination Survey (NHANES). NHANES data from 1999 to 2018 of women ≥ 50 years old with complete arthritis questionnaires and other data of interest were reviewed. Reproductive factors were analyzed as continuous and ordinal variables. Covariates included age, race/ethnicity, body mass index (BMI), poverty income ratio, smoking status, and comorbidities such as hypertension, cardiovascular disease, and diabetes. A total of 10,133 women were included in the analysis. A later age at menarche was associated with a lower likelihood of OA (adjusted odds ratio [aOR] = 0.91, 95% confidence interval [CI]: 0.87-0.95, p < 0.001), and higher parity was associated with a lower likelihood of OA (aOR = 0.94, 95% CI: 0.91-0.97, p < 0.001). Stratified analysis showed that these associations were evident in specific subgroups, including women aged 60-69 years and those with obesity, but were not observed in other groups. Later age at menarche and higher parity are associated with a lower likelihood of OA in women. The cross-sectional nature of the study limits causal inferences; thus, further research is needed to explore potential causality.
METTL14 aggravates pyroptosis in diabetic cardiomyopathy by promoting m6A modification of NLRP3.
Hua Z, Zhong F, Xu C … +1 more , Liang S
Immunol Res · 2025 Oct · PMID 41091242 · Publisher ↗
Diabetic cardiomyopathy (DCM) is an irreversible chronic cardiovascular complication of diabetes with a high mortality rate. This study aimed to explore the role of methyltransferase-like 14 (METTL14)-mediated m6A modifi...
Diabetic cardiomyopathy (DCM) is an irreversible chronic cardiovascular complication of diabetes with a high mortality rate. This study aimed to explore the role of methyltransferase-like 14 (METTL14)-mediated m6A modification in DCM. Here, DCM mouse models and high glucose (HG)-induced H9C2 cell models were employed. Cell phenotype was assessed using CCK-8 assay, lactate dehydrogenase (LDH) assay, Western blot, and flow cytometry. The underlying mechanism was investigated using quantitative real-time PCR (qPCR), methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assay. The results showed that METTL14 was upregulated in vitro and in vivo. Downregulation of METTL14 inhibited pyroptosis and myocardial damage. Mechanistically, METTL14 enhanced NLRP3 stability through m6A modification of NLRP3. Moreover, the m6A reader protein YTHDF1 (YTH N6-methyladenosine RNA-binding protein 1) mediated NLRP3 upregulation. This study revealed a novel mechanism by which METTL14-mediated m6A methylation regulates DCM progression, providing a potential therapeutic target for DCM.
Systematic correlation analysis of human CD molecules reveals upregulated co-expression of CD58, CD63, and CD147 in patients with primary Sjögren's syndrome.
Jiang C, Xiong Z, Guan Z … +7 more , Xie D, Li T, Bahabayi A, Zhang Z, Gao Y, Liu C, Wang P
Immunol Res · 2025 Oct · PMID 41087625 · Publisher ↗
Clusters of Differentiation (CD) molecules are cell surface molecules that exhibit dynamic expression on immune cells. This plasticity characteristic of CD molecules is the basis for the high abundance and diversity of i...
Clusters of Differentiation (CD) molecules are cell surface molecules that exhibit dynamic expression on immune cells. This plasticity characteristic of CD molecules is the basis for the high abundance and diversity of immune cell phenotypes. However, phenotypic associations of immune cells due to co-expression and mutual exclusion expression lead to some extent to a narrowing of the size of the immunophenotype repertoire. Therefore, a systematic exploration of the expression correlation including co-expression and mutual exclusion expression between CD molecules can help to reveal the co-phenotype and lost phenotypes during immunophenotyping analysis. In this study, using bioinformatics methods, we first confirmed that the conventional widely used Pearson and Spearman correlations are only suitable for co-expression but not for mutual exclusion expression analysis. Using bulk and single-cell RNA sequencing data, we systematically investigated the expression correlation and anti-correlation or mutual exclusion of 386 protein-encoding CD molecules in human CD4 T cells, CD8 T cells, B cells, NK cells, and monocytes. Highly correlated co-expression networks were identified in these cell types. Using flow cytometry, three CD molecules including CD58, CD63, and CD147 were experimentally validated to be significantly co-expressed in T cells. In particular, CD58 and CD147 showed a high correlation in either CD4 or CD8 T cells. Co-expression was also observed in T cells from patients with primary Sjögren's syndrome (pSS) and was found to be positively correlated with the increased cytotoxic potential of T cells. In addition, the combination of CD58 and CD147 provided a more precise definition of the T-cell phenotype, which would be beneficial for improving the diagnostic efficiency of pSS.
Anlotinib promotes CD4 + T cell infiltration and enhances the anti-tumor effect of PD-1 blockade in lung cancer.
Zhang M, Liu L, Zheng H … +2 more , Chen M, Li J
Immunol Res · 2025 Oct · PMID 41083765 · Publisher ↗
It has been reported that anlotinib exhibits antitumor efficacy in various cancers. However, the potential mechanisms by which anlotinib affects the immunosuppressive characteristics observed in tumor angiogenesis have n...
It has been reported that anlotinib exhibits antitumor efficacy in various cancers. However, the potential mechanisms by which anlotinib affects the immunosuppressive characteristics observed in tumor angiogenesis have not been fully elucidated. Therefore, we aimed to determine the potential of anlotinib in improving the effectiveness of PD-1/PD-L1 blockade therapy in lung cancer. An LLC mouse model was established by xenograft tumor model to evaluate the synergistic effects of anlotinib and anti-PD-1. Furthermore, changes in tumor vascular structure and T-cell infiltration were assessed using immunohistochemistry and flow cytometry. Clinical information from 198 lung cancer patients was collected to further analyze the relationship between Ki67 expression and patient survival as well as the synergistic effects. The study demonstrated that anlotinib successfully inhibited LLC cell growth. Additionally, anlotinib reduced related protein expressions in JAK2/STAT3 pathway. Mice in the anlotinib group exhibited lower expression levels of PD-L1 and VEGF-A and decreased intratumoral microvascular density. Moreover, PD-1/PD-L1 blockade combined with anlotinib promoted CD4 + T-cell infiltration into tumors, ultimately enhancing antitumor activity. Clinically, lung cancer patients treated with anlotinib and anti-PD-1 showed reduced Ki67 expression and improved survival rates. In conclusion, anlotinib improves tumor vascular structure and CD4 + T-cell infiltration by downregulating JAK2/STAT3 signaling, thereby enhancing the efficacy of PD-1 blockade in lung cancer.
Characterisation and diagnostic model of monogenic lupus.
Yang M, Lu D, Li Y … +4 more , Chen X, Yang H, Mo W, Mao H
Immunol Res · 2025 Oct · PMID 41083628 · Publisher ↗
Standardised diagnostic criteria for monogenic lupus are lacking owing to its rarity, diverse phenotypes, and significant heterogeneity in pathogenesis, phenotypic characteristics, disease course, and outcomes. Further,...
Standardised diagnostic criteria for monogenic lupus are lacking owing to its rarity, diverse phenotypes, and significant heterogeneity in pathogenesis, phenotypic characteristics, disease course, and outcomes. Further, no studies have analysed the characteristics of multiple pathological mechanisms of monogenic lupus. Therefore, we retrospectively summarised the clinical characteristics, genotypes, and treatment of 36 patients with monogenic lupus with 16 different gene mutations admitted to the Department of Immunology at Beijing Children's Hospital between June 2021 and July 2024. Children with classic lupus were randomly allocated to the control group. A univariate analysis was conducted on different pathogenic pathways to identify relevant significant risk factors. The least absolute shrinkage and selection operator and logistic regression were applied to construct multiple models. The discrimination and calibration abilities of these models were then evaluated, and the optimal diagnostic model for each pathway was proposed. We found that increased vigilance for monogenic lupus is necessary for male children with an onset age of < 8.46 years and a family history. Type-I-interferon disorders should be considered in patients with growth retardation, interstitial lung disease, intracranial calcifications, characteristic rashes, splenomegaly, and elevated liver enzymes. Monogenic lupus involving immune tolerance pathways should be considered in patients with repeated infections, lymphoproliferation, or elevated double-negative T-lymphocyte proportion. Monogenic lupus caused by another pathway should be considered in patients with abdominal symptoms, oral ulcers, and elevated C-reactive protein levels. Overall, our study proposes distinct diagnostic models based on various pathogenic pathways, aiding in early identification and diagnosis of monogenic lupus in children.
Genomic and clinical characterization of adult CVID patients: results from a single-centre turkish cohort.
Yilmaz Tekinhatun H, Firtina S, Sayitoglu M … +1 more , Ar MC
Immunol Res · 2025 Oct · PMID 41071379 · Publisher ↗
Common Variable Immunodeficiency (CVID) is the most frequently encountered symptomatic primary immunodeficiency in clinical practice, presenting with heterogeneous clinical and genetic features. While traditionally consi...
Common Variable Immunodeficiency (CVID) is the most frequently encountered symptomatic primary immunodeficiency in clinical practice, presenting with heterogeneous clinical and genetic features. While traditionally considered polygenic, recent advances in genomic technologies have revealed monogenic causes in a significant subset of patients. This study aimed to investigate the genetic background of adult patients diagnosed with CVID or CVID-like phenotypes, using clinical exome sequencing (CES), focusing on atypical and syndromic presentations. Thirty adult patients fulfilling the ESID/PAGID criteria for CVID underwent CES. Genetic analysis targeted 451 immune-related genes, with variants interpreted according to ACMG guidelines. Pathogenicity was confirmed with Sanger sequencing. We detected potentially disease-related variants (TNFRSF13B, BTK, RAG1, SAMD9, NFKB2, PRKDC, CFTR, FCN3, IFIH1, ITGA3, and TNFRSF1A) in 12 of the 30 patients (40%). TNFRSF13B was the most frequently mutated gene among these patients. Deep phenotyping analyses revealed atypical findings included a hemizygous BTK variant mimicking CVID, a homozygous RAG1 variant consistent with leaky SCID, and a heterozygous SAMD9 variant not presenting with MIRAGE phenotype, and a homozygous ITGA3 insertion region variant that suggested a mild form of ILNED syndrome. Variants in CFTR, FCN3, and TNFRSF1A further expand the phenotypic spectrum, highlighting overlap between immunodeficiency and immune dysregulation syndromes in adulthood. A substantial proportion of adult patients with CVID-like phenotypes harbor variants in genes beyond the classical CVID-associated loci. Our findings support the utility of broad genetic screening in adult-onset antibody deficiency, particularly when non-infectious complications are present. Molecular diagnosis facilitates accurate classification, guides personalized treatment, and aids in genetic counseling.
The invisible agitators: exploring the viral interplay in psoriatic immune dysregulation.
Nayak S, Reddy BN, Kintali SV
Immunol Res · 2025 Oct · PMID 41044254 · Publisher ↗
This review explores the complex interplay between viral infections and psoriasis. It emphasizes how viruses like HIV, hepatitis, herpes, human papillomavirus, and SARS-CoV-2 can provoke and worsen psoriatic inflammation...
This review explores the complex interplay between viral infections and psoriasis. It emphasizes how viruses like HIV, hepatitis, herpes, human papillomavirus, and SARS-CoV-2 can provoke and worsen psoriatic inflammation by disturbing immune balance. A key focus of the discussion is the IL-23/Th-17 pathway, which drives the production of proinflammatory cytokines that promote keratinocyte overgrowth and perpetuate chronic skin inflammation. Our article further investigates how disrupted intracellular pathways-such as those involving PI3K, Wnt signaling, and caveolin-affect the severity of the disease. This review supports the idea that viral infections can not only trigger psoriatic lesions but may also increase the risk of additional viral reactivation, thereby complicating the clinical picture of psoriasis. This thorough evaluation highlights the necessity for focused research to create innovative therapeutic strategies aimed at these viral triggers.
Trained Immunity in sepsis: Exploring the molecular link to long-term cardiometabolic disorders.
Lahariya R, Anand G, Kumari B
Immunol Res · 2025 Oct · PMID 41032210 · Publisher ↗
Sepsis, a life-threatening systemic infection, has long been recognized for its immediate risks, but its long-term consequences on health are increasingly evident, particularly in predisposing survivors to chronic cardio...
Sepsis, a life-threatening systemic infection, has long been recognized for its immediate risks, but its long-term consequences on health are increasingly evident, particularly in predisposing survivors to chronic cardiometabolic disorders (CMDs) such as atherosclerosis, insulin resistance, and dyslipidemia. Central to this process is trained immunity, where innate immune cells like monocytes, macrophages, and neutrophils undergo long-lasting epigenetic reprogramming after sepsis. This reprogramming, sustained by molecular pathways such as NF-κB, mTOR, and altered lipid metabolism, drives chronic inflammation, oxidative stress, and metabolic dysfunction, contributing to long-term cardiovascular diseases (CVDs) and metabolic disorders post-sepsis. This review explores the key mechanisms through which trained immunity bridges sepsis and CMDs, particularly focusing on epigenetic modifications such as histone acetylation, DNA methylation, and mitochondrial alterations. We discuss how trained immunity enhances immune cell activation, leading to persistent low-grade inflammation, lipid dysregulation, and impaired insulin sensitivity, all of which predispose sepsis survivors to CVDs. Additionally, we highlight potential therapeutic approaches targeting trained immunity, including statins, which reduce inflammation and immune reprogramming; metformin, which restores metabolic balance by activating AMPK and reducing oxidative stress; dimethyl fumarate (DMF), a potent Nrf2 activator that counteracts inflammation; and probiotics, which help restore gut microbiota balance and limit endotoxin-driven inflammation. These therapies offer promising strategies to mitigate long-term metabolic dysfunction and reduce the incidence of CMDs following sepsis. Understanding these mechanisms and developing targeted interventions may ultimately help prevent chronic cardiovascular and metabolic diseases in sepsis survivors and improve long-term outcomes.
Sequence similarity-based candidate gene prioritization for Type 1 diabetes mellitus using moment of inertia tensor.
Vishnu E, Chandramohan N, Manimaran P
Immunol Res · 2025 Sep · PMID 41017002 · Publisher ↗
In this paper, the study focuses on Type 1 Diabetes Mellitus (T1D), a chronic condition that affects the insulin-producing cells of the pancreas, requiring individuals to depend on external insulin for survival. We intro...
In this paper, the study focuses on Type 1 Diabetes Mellitus (T1D), a chronic condition that affects the insulin-producing cells of the pancreas, requiring individuals to depend on external insulin for survival. We introduce a novel method for analyzing protein sequences by treating them as rigid bodies with mass and moment of inertia to assess sequence similarity. This method transforms the protein sequences into vectors using the moment of inertia tensor, with similarity calculated using Euclidean distance. Using this technique, we identified 24 genes linked to T1D, showing significant similarities to known T1D-related genes and highlighting their potential importance in the disease. Further, we conduct functional enrichment analysis for better understanding, which is very helpful for investigating their roles in various biological processes and molecular functions. The Gene Ontology (GO)analysis is crucial for prioritizing the identified genes and providing insights into their contributions to T1D pathophysiology. To combine the concepts from physics with computational biology, our research not only increases the understanding of T1D disease but also introduces an innovative approach for gene discovery and functional analysis in autoimmune diseases.
Piceatannol improves autoimmune hepatitis by inhibiting the immune activities of T cells and macrophages through binding with c-Jun.
Xu C, Lu C, Wang W … +5 more , Wang Z, Qiu Y, Han M, Yang J, Li S
Immunol Res · 2025 Sep · PMID 41014384 · Publisher ↗
Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A...
Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A mouse model of AIH was established by injecting ConA (i.v.), and PIC was administered as an intervention. The protective effect of PIC was evaluated by the liver function, liver pathology, and serum levels of inflammatory factors. Subsequently, network pharmacology was used to predict the pathways and targets of PIC in the treatment of AIH, and the predicted results were validated using flow cytometry, molecular docking, surface plasmon resonance (SPR) and so on. Finally, the immunosuppressive effect of PIC was further validated in a mouse heart transplantation model. PIC can improve liver function decline and reduce pathological liver damage, as well as inhibit the increase of serum inflammatory factor levels in mice with AIH induced by ConA. The protective effect is achieved by suppressing the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts and inhibit acute rejection reactions. These results indicated that PIC can significantly improve ConA-induced AIH in mice by inhibiting the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts in mice and inhibit acute rejection responses. The above results indicated that PIC may serve as a promising immunosuppressant and be effective for AIH.
Associative study of human herpesvirus 8 and Kaposi's sarcoma: Mapping viral oncogenic properties and the clinical scenario in oncological patients.
da Silva JVGO, Vieira JMBD, de Oliveira Santos E
Immunol Res · 2025 Sep · PMID 40974450 · Publisher ↗
Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiological agent of Kaposi's Sarcoma (KS) and other lymphoproliferative disorders. Over three decades after its discovery...
Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiological agent of Kaposi's Sarcoma (KS) and other lymphoproliferative disorders. Over three decades after its discovery, many aspects of its biology, latency, immune evasion, and oncogenic mechanisms remain poorly understood. This review provides an integrative and up-to-date analysis of KSHV, from its molecular architecture and gene regulation to its complex host interactions and transmission dynamics. We highlight key viral proteins-LANA, RTA, vFLIP, vCyc, kaposins, and viral miRNAs-that orchestrate latency maintenance, lytic reactivation, immune modulation, and tumor development. The review maps how KSHV establishes persistent infection, exploits host signaling pathways, and induces hallmarks of cancer, such as angiogenesis and uncontrolled proliferation. We also discuss glycoprotein-receptor interactions involved in viral entry and the structural mechanisms facilitating KSHV-cell fusion. Clinically, we present updated epidemiological data and analyze the diversity of KS forms-classic, endemic, iatrogenic, epidemic, and anaplastic-highlighting regional disparities, diagnostic challenges, and treatment gaps. The article emphasizes the virus's role in aggressive neoplasms in immunocompromised individuals and underscores the lack of antiviral strategies specifically targeting KSHV. By combining molecular virology, oncogenesis, immunology, and epidemiology, this review advances the current understanding of KSHV and reinforces the urgent need for effective diagnostic tools, preventive strategies, and targeted therapies. Our findings contribute to bridging knowledge gaps and promoting translational approaches to mitigate the global impact of KSHV-related diseases.
Engineering CAR-T cells for solid tumors: bispecific antigen targeting, tumor microenvironment modulation, and toxicity control.
Premchandani T, Qutub M, Tatode A … +4 more , Umekar M, Taksande J, Hussain UM, Khidkikar SR
Immunol Res · 2025 Sep · PMID 40973858 · Publisher ↗
Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematologic malignancies, yet its efficacy in solid tumors remains limited due to antigen heterogeneity, immunosuppressive tumor microe...
Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematologic malignancies, yet its efficacy in solid tumors remains limited due to antigen heterogeneity, immunosuppressive tumor microenvironments, and therapy-associated toxicities. This review highlights advances across CAR-T generations, emphasizing co-stimulatory domains and cytokine-armed TRUCKs to enhance persistence and function. Viral (lentiviral, gamma-retroviral) and non-viral (CRISPR, transposons, mRNA electroporation) delivery systems are compared for efficiency, safety, and scalability, with CRISPR enabling multiplex edits for improved specificity. Dual-targeting CARs counter antigen heterogeneity, while hypoxia-inducible and SynNotch CARs restrict activity to tumor sites. Chemokine receptor engineering enhances infiltration, and armored CARs secreting IL-12 or checkpoint inhibitors remodel the TME. Nanobody-based CAR-T cells further expand design versatility, offering improved stability, tumor penetration, and reduced immunogenicity compared with single-chain variable fragment constructs. Safety innovations include iCasp9 Suicide switches, dasatinib-controlled activation, and cytokine blockade. Clinical trials of bispecific CAR-Ts show promise, yet challenges Like manufacturing complexity and off-target effects persist. Integrating AI-driven design and Personalized neoantigen targeting may unlock CAR-T 2.0 for solid tumors, pending scalable production and regulatory harmonization.
The double-edged sword of PI3Kδ pathway-related immune dysregulation: insights from two case reports.
Cabanero-Navalon MD, Garcia-Bustos V, Ibanez-Barcelo S … +3 more , Balastegui-Martin H, Grimaldos-Lodares J, Moral-Moral P
Immunol Res · 2025 Sep · PMID 40971032 · Full text
Phosphoinositide 3-kinases (PI3Ks), particularly the PI3Kδ pathway, play a crucial role in regulating immune functions. Alterations in this pathway, either as hyperactivation, such as in activated PI3Kδ syndrome (APDS),...
Phosphoinositide 3-kinases (PI3Ks), particularly the PI3Kδ pathway, play a crucial role in regulating immune functions. Alterations in this pathway, either as hyperactivation, such as in activated PI3Kδ syndrome (APDS), or rarely described hypoactivation, profoundly influence immune function and are linked to a spectrum of immunodeficiencies and autoimmune conditions. This report describes two cases of late-onset immunodeficiencies associated with PI3Kδ pathway dysregulation, each presenting with unique mutations and clinical manifestations. The first case involves a heterozygous mutation in PI3KR1 (c.5A > T, p.Tyr2Phe) indicative of PI3Kδ hyperactivation, effectively managed with sirolimus. The second case is characterized by a homozygous mutation in PIK3CD (c.2608C > T, p.Arg870Ter), suggesting PI3Kδ hypoactivation, with clinical features including psoriatic arthritis and ulcerative colitis. These cases underscore the heterogeneous clinical features and the challenges in managing such rare genetic variants. These cases underscore the importance of considering primary immunodeficiency in individuals exhibiting signs of both infectious and non-infectious autoimmune or immune dysregulation complications. Prompt genetic screening and strategic therapeutic approaches are crucial for effectively managing these conditions and mitigating the risks associated with immunosuppressive treatments. These insights emphasize the need for a deeper understanding of genetic factors in immunodeficiencies to devise personalized treatment strategies that substantially improve patients' quality of life.
A rare autoinflammatory syndrome associated with a C2orf69 frameshift mutation: a case report.
Türkmen Ş, Yarar MH, Tosun İ … +2 more , Bozkurt HB, Sözeri B
Immunol Res · 2025 Sep · PMID 40971009 · Publisher ↗
Abstract loading — click title to view on PubMed.
Monocyte plasticity and HLA-DR expression in patients with X-linked agammaglobulinemia.
Artac H, Ceylan A, Kulhas Celik I … +26 more , Celebi Celik F, Karali Y, Meric Z, Tekcan D, Geyik M, Bozkurt S, Esenboga S, Haskoloğlu ZŞ, Ozek Yucel E, Gulez N, Edeer Karaca N, Bilgic Eltan S, Guner SN, Aydogmus C, Celiksoy MH, Karabiber E, Genel F, Doğu EF, Karakoc-Aydiner E, Cagdas D, Aksu G, Kiykim A, Kilic SS, Keleş S, Ikinciogullari KA, Reisli İ
Immunol Res · 2025 Sep · PMID 40970998 · Publisher ↗
Bruton's tyrosine kinase (BTK) is expressed by innate immune cells, and it has been suggested that a lack of BTK may affect monocytes, impacting infection susceptibility and inflammatory response in patients with X-linke...
Bruton's tyrosine kinase (BTK) is expressed by innate immune cells, and it has been suggested that a lack of BTK may affect monocytes, impacting infection susceptibility and inflammatory response in patients with X-linked agammaglobulinemia (XLA). This study aimed to explore the role of monocyte subsets and monocyte human leucocyte antigen DR (mHLA-DR) expression in patients with XLA. Fifty-nine patients diagnosed with XLA and 37 age-matched healthy subjects were enrolled, and their demographic and clinical features were recorded. Three monocyte subsets were identified-classical (CL) (CD14CD16), intermediate (INT) (CD14CD16), and non-classical (NC) (CD14CD16)-and their mHLA-DR expressions (mean fluorescence intensity, MFI) were determined by flow cytometry. We evaluated monocyte plasticity as the classical/intermediate monocyte (CMIM) ratio. Patients with XLA comprised 38 children (mean age, 10.46 ± 4.81 years) and 21 adults (25.09 ± 6.18 years). Compared to the control group, patients had decreased classical (p = .012) but increased intermediate and non-classical monocytes (p < .001 and p = .048, respectively). They also presented with increased mHLA-DR expression of total monocytes and their subsets compared to the healthy subjects (p < .05). There were 17 patients with bronchiectasis (28.8% of total, three children and 14 adults), and they had decreased mHLA-DR of non-classical monocytes and a low CMIM ratio compared with non-bronchiectasis XLA patients (p < .001). The study findings may indicate that a defect in adaptive immune mechanisms leads to compensatory changes in the innate immune system. Monocyte HLA-DR expression and CMIM ratio can be used as potential biomarkers to predict chronic complications, including bronchiectasis in patients with XLA.
Tyro3 upregulation is associated with muscle involvement in patients with idiopathic inflammatory myopathies.
Liu H, Ren Y, Li Q … +5 more , Si Y, Chen Y, Dong M, Yin G, Xie Q
Immunol Res · 2025 Sep · PMID 40958037 · Publisher ↗
Tyro3, Axl, and Mer (TAM) receptors are involved in immunity and affect the progression of several autoimmune diseases. This study investigated the potential role of TAM receptors in individuals diagnosed with idiopathic...
Tyro3, Axl, and Mer (TAM) receptors are involved in immunity and affect the progression of several autoimmune diseases. This study investigated the potential role of TAM receptors in individuals diagnosed with idiopathic inflammatory myopathies (IIM). Clinical data and serum samples were obtained from 176 patients with IIM and 50 healthy controls (HCs). The levels of soluble TAM (sTAM) receptors were measured through enzyme-linked immunosorbent assay. Additionally, Tyro3 protein expression in the muscle tissue of both patients and HCs was examined using western blot and immunohistochemistry (IHC) analyses. The levels of sTAM receptors were notably higher in IIM patients than in HCs. Specifically, serum concentrations of soluble Tyro3 (sTyro3) were markedly elevated among patients with dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM). No significant differences were found in sTyro3 levels among IMNM patients with anti-signal recognition particle positive, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase positive, and seronegative subtypes. Further, levels of sTyro3 showed an inverse relationship with the manual muscle testing-8 score, while exhibiting a positive correlation with serum creatine kinase. Following treatment, patients with IMNM and DM exhibited reduced sTyro3 levels. Results from western blotting and IHC revealed a significant expression of Tyro3 in the necrotic muscles of patients with IMNM and DM. This study demonstrated that Tyro3 causes muscle injury in patients with IIM; therefore, it is considered a potential biomarker and therapeutic target for patients with IIM.
Optimizing antiphospholipid antibody testing: a real-world analysis of appropriateness and resource utilization.
Foddai SG, Infantino M, Manfredi M … +7 more , Pavia F, Benucci M, Li Gobbi F, Radin M, Cecchi I, Barinotti A, Sciascia S
Immunol Res · 2025 Sep · PMID 40958002 · Full text
Efficient utilization of healthcare resources, including laboratory testing, is crucial for environmental sustainability and cost-effectiveness. The diagnosis of APS requires the presence of at least one clinical event (...
Efficient utilization of healthcare resources, including laboratory testing, is crucial for environmental sustainability and cost-effectiveness. The diagnosis of APS requires the presence of at least one clinical event (either an objectively confirmed thrombotic event and/or pregnancy complication) and detection of one or more aPL (lupus anticoagulant [LA], IgG/IgM anticardiolipin [aCL], and/or IgG/IgM anti-β2 glycoprotein-1 [aβ2GPI]). However, inappropriate requests for aPL tests contribute to unnecessary healthcare expenses and environmental impact. This study evaluates the appropriateness of aPL testing in a clinical setting. A retrospective analysis was conducted on 642 patients attending the San Giovanni Di Dio Hospital, Florence (11/2023-02/2024). Diagnostic suspicion underlying aPL test requests were classified as appropriate, inappropriate, or unevaluable using a scoring system based on clinical recommendations. Appropriateness assessment was performed independently by two researchers and reconciled with a third expert. Patient demographics, test results, and the specialty of the physicians ordering aPL were recorded and analyzed. Of the 642 queries, 36% were deemed appropriate, 42% inappropriate, and 22% unevaluable. Family physicians accounted for 53% of all test requests but exhibited the highest rate of inappropriate requests (44%). Rheumatologists, internal medicine physicians, and gynecologists demonstrated better adherence to recommendations (with 34%, 30%, and 18% of inappropriate requests, respectively). Only 4.9% of patients underwent comprehensive aPL testing per international standards (Sidney criteria). Among the 115 aPL-positive cases, multiple antibody positivity was more common in appropriate test requests. Inappropriate requests often stemmed from conditions without established links to APS, such as alopecia, hypercholesterolemia, and dysmenorrhea. A considerable proportion of aPL testing in routine practice lacks clinical justification, reflecting variability in guideline adherence across specialties. Inappropriate testing increases healthcare costs, specialist referrals, and environmental burdens. Improved education, adherence to diagnostic recommendations, and sustainable practices are critical to optimizing APS testing and resource utilization.
Multi-class machine learning-based classification of SCID-related genetic variants.
Şahin A, Sonmez G, Karaselek M … +1 more , Reisli İ
Immunol Res · 2025 Sep · PMID 40931232 · Publisher ↗
BACKGROUND: Variants of uncertain significance (VUS) represent a major diagnostic challenge in the interpretation of genetic testing results, particularly in the context of inborn errors of immunity such as severe combin...
BACKGROUND: Variants of uncertain significance (VUS) represent a major diagnostic challenge in the interpretation of genetic testing results, particularly in the context of inborn errors of immunity such as severe combined immunodeficiency (SCID). The inconsistency among computational prediction tools often necessitates expensive and time-consuming wet-lab analyses. OBJECTIVE: This study aimed to develop disease-specific, multi-class machine learning models using in silico scores to classify SCID-associated genetic variants and improve the interpretation of VUS. METHODS: Genes associated with SCID were identified based on the 2024 update of the International Union of Immunological Societies. Missense variants were retrieved from ClinVar and labeled as benign, likely benign, likely pathogenic, or pathogenic. Variants classified as VUS or with conflicting interpretations were excluded. In silico functional prediction scores were collected for each variant. Multi-class classification models were developed using six machine learning algorithms: Random Forest, XGBoost, Gradient Boosting, AdaBoost, Support Vector Machine and Logistic Regression. Performance was evaluated using five-fold cross-validation with five repeats (25 folds). RESULTS: A total of 537 variants from 71 genes were included in the final dataset. Among the models, Random Forest achieved the best performance with an accuracy of 0.70 ± 0.03 and the highest area under the receiver operating characteristic curve (AUROC: 0.90 ± 0.01). MetaRNN, BayesDel_addAF, and REVEL were the most predictive features. CONCLUSION: This study demonstrates that disease-specific, multi-class machine learning models leveraging in silico scores can effectively support the classification of SCID-related variants, offering a promising tool for improving VUS interpretation. KEY MESSAGES: Multi-class machine learning models can enhance the interpretation of SCID-related VUS. Random Forest showed the highest diagnostic accuracy and robustness among tested models. Disease-specific modeling improves classification performance despite limited datasets. Capsule Summary This study developed disease-specific multi-class machine learning models to classify SCID-related variants using in silico scores, with Random Forest showing the strongest performance in predicting variant pathogenicity.
Collagen heterogeneity: a barrier and bridge driving tumor immune microenvironment remodeling.
Xie Y, Chen P, Qi C … +1 more , Zheng L
Immunol Res · 2025 Sep · PMID 40921908 · Publisher ↗
The tumor microenvironment (TME) is a complex system composed of the extracellular matrix (ECM) and various cell types, with collagen being one of its core components. Collagen heterogeneity profoundly influences tumor p...
The tumor microenvironment (TME) is a complex system composed of the extracellular matrix (ECM) and various cell types, with collagen being one of its core components. Collagen heterogeneity profoundly influences tumor progression and the remodeling of the immune microenvironment by regulating tumor cell behavior, signaling pathways, and immune evasion in TME. Different subtypes of collagen significantly affect tumor growth, metastasis, and therapeutic responses by modulating the infiltration and function of immune cells. In "cold" tumors, the immunosuppressive microenvironment is shaped by collagen deposition, fibroblast activation, and the release of immunosuppressive factors. The excessive accumulation of collagen hinders immune cell infiltration and the efficacy of immunotherapy. Now, therapeutic strategies targeting collagen metabolism have shown promise in converting cold tumors into "hot" tumors by reducing collagen deposition and enhancing tumor immunity. This review systematically explores how different collagen subtypes regulate collagen metabolism offering new perspectives for the treatment of cold tumors and laying the theoretical groundwork for future advances in personalized immunotherapy.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe