Frontiers in Immunology最新文献

{"title":"Safety profile of complement C5 inhibitors and FcRn inhibitors in the treatment of myasthenia gravis: analysis of the FAERS database and disease-gene interaction network.","authors":"Luqiong Wang, Jiaojiao Chen, Huixiang Li, Lin Wang, Feiyu Liu, Xiaoli Jiang","doi":"10.3389/fimmu.2025.1667249","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1667249","url":null,"abstract":"<p><strong>Objective: </strong>To integrate pharmacovigilance and network pharmacology methods for a comprehensive analysis of the potential adverse reactions of complement C5 inhibitors (eculizumab, ravulizumab, zilucoplan) and neonatal Fc receptor (FcRn) inhibitors (efgartigimod, rozanolixizumab), and to explore their toxicity mechanisms, thereby providing a reference for rapidly understanding the safety of these two novel classes of biologics in the treatment of myasthenia gravis (MG).</p><p><strong>Methods: </strong>We extracted adverse event (AE) reports for these five drugs from the FDA Adverse Event Reporting System (FAERS) database, limited to the period since their FDA approval for the treatment of MG. Reports were further restricted to those where the drug was listed as the primary suspect (PS) and the indication (INDI) was \"MG\". Signal detection was performed using the Reporting Odds Ratio (ROR) method, the UK Medicines and Healthcare products Regulatory Agency (MHRA) method, and the Bayesian Confidence Propagation Neural Network (BCPNN) method. Additionally, network pharmacology was employed to analyze the toxicity mechanisms of the system organ categories (SOCs) specifically associated with complement C5 inhibitors and FcRn inhibitors.</p><p><strong>Results: </strong>Signal detection of AE reports associated with these five drugs revealed previously unlabeled positive signals, including: eculizumab (gastric cancer, embolic stroke), ravulizumab (psoriatic arthropathy, hypoacusis, peripheral vascular disorders), zilucoplan (weight increased, weight decreased), efgartigimod (metastases to liver, hepatic failure, nephrolithiasis, dysuria, Prostatitis, prostate cancer, Angina pectoris, congestive cardiac failure) and rozanolixizumab (vomiting, dyspepsia). However, the gastric cancer, liver metastasis and prostate cancer were reported within the first 30 days, causal associations cannot be established based on the data presented. Potential toxicity analysis was conducted on noteworthy SOCs for complement C5 inhibitors and FcRn inhibitors, revealing key targets and pathways.</p><p><strong>Conclusion: </strong>This study elucidated the safety profiles of complement C5 inhibitors and FcRn inhibitors in clinical practice through pharmacovigilance analysis, confirming known adverse reactions and identifying several previously unreported ones. Furthermore, network pharmacology analysis revealed potential mechanisms underlying these adverse reactions. These findings provide valuable insights for monitoring and managing risks during treatment with two novel classes of biologics.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1667249"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Lactobacillus plantarum</i>-derived cytoplasmic membrane vesicles as novel anti-inflammatory nanotherapeutics for psoriasis management.","authors":"Yuedong Xie, Guowen Lv, Dandan Su, Manchun Li, Quanle Xu, Hongbo Chen, Fang Cheng, Dongling Dai","doi":"10.3389/fimmu.2025.1647466","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1647466","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Current research underscores the critical role of the gut-skin axis in inflammatory skin disorders such as psoriasis, with growing interest in the therapeutic application of probiotics. Despite this promise, the specific mechanisms and bioactive compounds through which probiotics exert their effects remain poorly characterized. In this study, we aimed to systematically evaluate the therapeutic potential of &lt;i&gt;Lactobacillus plantarum&lt;/i&gt; (Lp)-derived bioactive fractions in psoriasis, with a particular focus on identifying key anti-inflammatory and immunomodulatory metabolites.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The microbiome characteristics of psoriasis were analyzed through open microflora data mining and bibliometrics, and the probiotics with potential therapeutic effects were identified. Four bioactive fractions from &lt;i&gt;L. plantarum&lt;/i&gt; were extracted and characterized. CCK-8, qPCR, and flow cytometry were used to evaluate the effects of four bioactive components on oxidative stress in keratinocytes and inflammatory responses in macrophages. Metabolomics was used to analyze the metabolic profiles of bioactive components with anti-inflammatory and antioxidant properties, and to screen and identify the main metabolite that play a role. To evaluate the efficacy and safety of bioactive components in the treatment of IMQ-induced psoriasis in mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A common feature of downregulation of &lt;i&gt;Lactobacillus&lt;/i&gt; abundance was shown in patients with four inflammatory skin diseases including psoriasis. Four bioactive fractions, namely cytoplastic membrane vesicles (CMVs), bacterial lysate supernatant (BL-S), bacterial lysate precipitate (BL-P) and cell-free fermentation supernatant (CFS), were extracted from &lt;i&gt;L. plantarum&lt;/i&gt; ATCC BAA-793, and CMVs were identified as having typical extracellular vesicles. In efficacy evaluation, CMVs and BL-S significantly reduced the mRNA levels of inflammatory factors in macrophages and the ROS levels of inflamed keratinocytes, among which CMVs had a more significant anti-inflammatory effect and had a unique inhibitory effect on M1 polarization of macrophages. Metabolomics revealed significant differences in metabolite profiles between CMVs and BL-S, and AEA enriched in both played anti-inflammatory, antioxidant and inhibitory roles in macrophage M1 polarization. In IMQ-induced psoriasis mouse models, CMVs demonstrated superior effects over BL-S in anti-hyperkeratosis, inhibiting inflammatory factor production, and down-regulating the proportion of M1 macrophages in skin and spleen. Both showed good biosafety &lt;i&gt;in vivo&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This study demonstrates that &lt;i&gt;L. plantarum&lt;/i&gt;-derived CMVs, enriched with AEA, ameliorate psoriasis through multi-faceted mechanisms including anti-inflammation, antioxidative stress reduction, and reprogramming of macrophage polarization. These findings not only position bacterial nanovesicles as a ","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1647466"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Novel advances on pathophysiological mechanisms, clinical manifestations, and treatment of antiphospholipid syndrome.","authors":"Qing-Nan Zhu, Xiang-Bo Qi, Shu-Wei Ren, Yu-Ye Li, Ze-Wen Yan, Yu Sun, Yan Shi, Qing-Si Wen, Mao-Mao Wu, Da-Peng Wang","doi":"10.3389/fimmu.2025.1711668","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1711668","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2025.1639065.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1711668"},"PeriodicalIF":5.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12541817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting senescent microglia in progressive multiple sclerosis: a geroscience-informed approach.","authors":"Jeffrey Atkinson, Amy Dokiburra, Hayley Groover, Jonathan P Godbout, Benjamin M Segal, Yinan Zhang","doi":"10.3389/fimmu.2025.1681724","DOIUrl":"10.3389/fimmu.2025.1681724","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS). Age is the strongest predictor of disease phenotype, with the majority of older adults transitioning to a progressive form marked by irreversible neurological decline. This clinical progression is associated with smoldering, CNS-compartmentalized inflammation and neurodegeneration, for which there are currently no effective disease-modifying therapies. Cellular senescence, characterized by the secretion of pro-inflammatory mediators collectively known as the senescence-associated secretory phenotype (SASP), increases with age and contributes to tissue injury. In MS, neuroinflammation can further promote cellular senescence, creating a self-reinforcing cycle of damage. Senescent microglia have been identified within MS lesions, where their SASP may impair remyelination and exacerbate neurodegeneration. Senolytic agents selectively target and eliminate senescent cells by disrupting anti-apoptotic pathways. In experimental autoimmune encephalomyelitis (EAE), a widely used model of MS, senolytic treatment reduces senescent microglia burden and attenuates disease severity in an age- and drug-dependent manner. Specifically, here we show that middle-aged mice (40-44 weeks) with EAE exhibit improved clinical outcomes and survival following treatment with either dasatinib plus quercetin (D+Q) or navitoclax. Early-phase clinical trials of senolytics in age-related diseases have demonstrated functional benefits, including improved gait speed in idiopathic pulmonary fibrosis and CNS penetrance in Alzheimer's disease. Translating senolytic therapy to MS will require careful selection of CNS-penetrant and well-tolerated agents, identification of appropriate patient populations, and deployment of responsive biomarkers. Senolytic therapy represents a promising geroscience-based strategy to meet the urgent therapeutic need in progressive MS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1681724"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary antibody deficiencies in the modern era: emerging trends, diagnostic pitfalls, and advances in personalised management.","authors":"Shuayb Elkhalifa, Fulvio Salvo, Haggar Elbashir, Irfan Shafiq, Saed Isse, Mohamed Abuzakouk, Mohamed Medhat Gaber, Rehan Bhana","doi":"10.3389/fimmu.2025.1635094","DOIUrl":"10.3389/fimmu.2025.1635094","url":null,"abstract":"<p><p>Secondary antibody deficiencies (SADs) are a significant but frequently under-recognised group of acquired immunodeficiencies. They may arise in various clinical settings, including haematological malignancies, immunosuppressive therapies, and protein-losing conditions. SADs are associated with an increased risk of recurrent and severe infections, hospitalisation, and impaired quality of life. Despite this, diagnostic and treatment pathways remain inconsistent across healthcare settings and regions. Recent advances in the use of structured clinical data, including electronic health records and systematic laboratory assessments, show promise in facilitating earlier recognition of SADs. These approaches support more timely treatment decisions and promote consistent standards of care. Achieving improved outcomes for individuals with SADs will require broader consensus on diagnostic criteria, treatment thresholds, and access to specialist immunology services.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1635094"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma.","authors":"Dongdong Zhang, Pei Zhang, Ran Jing, Ziwei Chen, Ming Cai","doi":"10.3389/fimmu.2025.1687140","DOIUrl":"10.3389/fimmu.2025.1687140","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1687140"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram for predicting postoperative recurrence in patients with microvascular invasion-negative hepatocellular carcinoma: development and validation.","authors":"Qingwang Ye, Yi Yu, Shujie Pang, Dongbo Zhao, Dongqian Li, Yao Ma, Ning Yang, Wei Feng","doi":"10.3389/fimmu.2025.1614392","DOIUrl":"10.3389/fimmu.2025.1614392","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) imposes a substantial global health burden, while postoperative recurrence remains a pivotal factor contributing to poor prognosis. Although existing prognostic models predominantly focus on patients with HCC with microvascular invasion (MVI), recurrence mechanisms and risk stratification in those with MVI-negative HCC remain underexplored despite their distinct clinicopathological profiles. As such, this study aimed to develop a prognostic nomogram to predict recurrence-free survival (RFS) in patients with MVI-negative HCC.</p><p><strong>Methods: </strong>Data from 547 treatment-naïve patients with MVI-negative HCC were divided into 2 cohorts: training (n=375); and external validation (n=172). Random survival forest and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram prediction model was developed based on risk factors identified in the training cohort and subsequently validated in the external validation cohort.</p><p><strong>Results: </strong>Key findings revealed that Ki-67, alpha-fetoprotein (AFP)-L3, neutrophil-to-lymphocyte ratio, AFP, and systemic immune-inflammation index significantly impacted RFS, with a concordance-index (C-index) exceeding 0.7 for the nomogram model in the training cohort, and an area under the receiver operating characteristic curve (AUC) of 0.758, 0.769, and 0.779 for 1-, 3-, and 5-year RFS, respectively. The external validation cohort corroborated these findings, achieving C-index values > 0.7 and AUC values of 0.717, 0.735, and 0.756 for the same time points. The calibration curves indicated strong agreement between the predicted and actual outcomes. Decision curve analysis revealed that the nomogram model demonstrated good net benefits for 1-, 3-, and 5-year RFS in both the training and external validation cohorts.</p><p><strong>Conclusion: </strong>This study developed and validated a prognostic nomogram for predicting postoperative disease recurrence in patients with MVI-negative HCC, highlighting the importance of individualized patient management based on the risk factors identified.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1614392"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophils as predictive biomarkers in anti-programmed cell death 1 monotherapy for non-small cell lung cancer.","authors":"Takahiro Uchida, Kazuyuki Nakagome, Kosuke Hashimoto, Hidetoshi Iemura, Yuki Shiko, Atsuto Mouri, Ou Yamaguchi, Yoshitaka Uchida, Yoshiaki Nagai, Tomoyuki Soma, Kyoichi Kaira, Makoto Nagata, Hiroshi Kagamu","doi":"10.3389/fimmu.2025.1574314","DOIUrl":"10.3389/fimmu.2025.1574314","url":null,"abstract":"<p><strong>Background: </strong>The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.</p><p><strong>Methods: </strong>We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.</p><p><strong>Results: </strong>The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4⁺ (r = 0.43, p = 0.0045) and CD8⁺ T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4⁺ T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8⁺ T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.</p><p><strong>Conclusion: </strong>Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574314"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering macrophage differentiation and cell death dynamics in heart failure: a single-cell sequencing odyssey.","authors":"Jin Wei, Yao Sun, Bao-Xi Qu, Xin-Xin Duan, Li-Hong Yan, Wei An, Kun-Lun Yin, Shui-Yun Wang, Yan-Hai Meng, Lei Huang","doi":"10.3389/fimmu.2025.1604226","DOIUrl":"10.3389/fimmu.2025.1604226","url":null,"abstract":"<p><strong>Aims: </strong>We hypothesize that specific macrophage differentiation trajectories in heart failure (HF) are coupled with subtype-specific and context-dependent engagement of programmed cell death (PCD) pathways, particularly ferroptosis and anoikis, which in turn influence disease progression and remodeling. HF is a progressive and heterogeneous clinical syndrome characterized by adverse immune remodeling, yet the precise contributions of macrophage heterogeneity, lineage dynamics, and PCD programs to its pathogenesis remain unclear. This study aimed to delineate, at single-cell resolution, the cellular and molecular landscape of cardiac macrophage subpopulations and their engagement with immunogenic cell death programs.</p><p><strong>Methods: </strong>We profiled human cardiac tissues from HF and non-failing donors using scRNA-seq from the SCP1303 dataset, initially comprising ~600,000 cells and reduced to ~120,000 high-quality cells from 18 samples after stringent quality control to retain biologically valid but metabolically distinct populations. Standardized cell-type annotation and pseudotime trajectory reconstruction were applied. Pathway activity was quantified using AUCell (primary) and GSVA (complementary) for cell death-related signatures. Integrated differential expression analysis, protein-protein interaction network mapping, and multi-algorithm feature selection (LASSO, SVM-RFE, Random Forest) were performed, and candidate biomarkers were validated using an independent bulk RNA-seq dataset (GSE57345).</p><p><strong>Results: </strong>Thirteen major cardiac cell types were identified, with macrophages showing the highest transcriptional heterogeneity. We resolved four macrophage subtypes and mapped bifurcating disease-associated differentiation trajectories, revealing distinct activation patterns of ferroptosis- and anoikis-related pathways. Ferroptosis-associated genes and anoikis-associated genes displayed subtype-specific enrichment and significant differential activation in HF. Pseudotime analysis demonstrated that suppression of ferroptosis and anoikis was linked to late-stage, HF-enriched macrophage states. Key biomarkers-including CD163, FPR1, and VSIG4-achieved robust diagnostic performance (AUC > 0.80) in discriminating HF phenotypes.</p><p><strong>Conclusions: </strong>This is the first study to integrate scRNA-seq, differentiation trajectory inference, and PCD pathway scoring to define the context-dependent engagement of ferroptosis and anoikis in macrophage subtypes in HF. The identification of subtype-specific biomarkers and functional states provides novel mechanistic insight and potential diagnostic and therapeutic targets, underscoring the value of high-resolution immune profiling for precision immunology in cardiovascular disease.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1604226"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and immunological spectrum of MHC class I deficiency: insights from a long-term cohort with two novel mutations.","authors":"Sule Haskologlu, Aydan Ikinciogullari, Candan Islamoglu, Sevgi Kostel Bal, Deniz Bayrakoglu, Serife Erdem, Zeynep Ceren Karahan, Omur Ardeniz, Caner Aytekin, Aylin Heper, Serdar Ceylaner, Figen Dogu","doi":"10.3389/fimmu.2025.1675097","DOIUrl":"10.3389/fimmu.2025.1675097","url":null,"abstract":"<p><strong>Background: </strong>Major histocompatibility complex (MHC) Class I deficiency is a rare form of primary immunodeficiency that typically presents with recurrent sinopulmonary infections, bronchiectasis, and granulomatous skin lesions during late childhood or adolescence.</p><p><strong>Methods: </strong>This retrospective study describes the clinical, immunological, and long-term follow-up data of 11 patients diagnosed MHC Class I deficiency.</p><p><strong>Results: </strong>The cohort included 11 patients (6 males, 5 females) with a median age of 26 years (range 19-44). The median age at diagnosis was 19 years, with a diagnostic delay of 14 years. Bronchiectasis was seen in 10 patients, granulomatous skin lesions in 6, uveitis in 5, and nasal septum perforation in 3. All but one patient survived during a median follow-up of 11 years. HLA-ABC expression ranged from 0% to 73%, with persistently low mean fluorescence intensity (0.4-3.8). IgM levels were reduced in 7 patients. Ten patients were persistently positive for anti-rubella IgM, including all six with granulomatous skin lesions. Immunophenotyping revealed reduced CD3⁺ (n=2), CD4⁺ (n=3), CD8⁺ (n=3), CD19⁺ (n=5), CD3^-CD16⁺CD56⁺ (n=3), CD19+ IgM-27+ IgD- (switched memory B cells) (n=7), and CD19+ IgM-27+ IgD+ (marginal zone B cells) (n=8). All patients had elevated γδ+ T cells, and NK cells were reduced in three. Seven patients had TAP1 and four had TAP2 mutations, with no significant genotype-phenotype differences.</p><p><strong>Conclusion: </strong>MHC Class I deficiency presents a broad clinical spectrum from asymptomatic to life-threatening disease. Granulomatous tissue damage and uveitis contributed to morbidity. Persistent rubella-specific IgM in most patients, including those without granulomas, is a novel serologic finding that may reflect altered antiviral immunity. Its clinical significance remains uncertain and, further studies with tissue-based viral detection are needed to clarify this observation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1675097"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}