Frontiers in Immunology最新文献

{"title":"Hexokinase2-engineered T cells display increased anti-tumor function.","authors":"Raphaëlle Toledano Zur, Shiran Didi Zurinam, Maria Radman, Elia Funaro Balouka, Tatiana Borodianskiy-Shteinberg, Dieter Saur, Cyrille J Cohen","doi":"10.3389/fimmu.2025.1477929","DOIUrl":"10.3389/fimmu.2025.1477929","url":null,"abstract":"<p><strong>Background: </strong>T cells face significant metabolic challenges in the tumor microenvironment (TME), where cancer cells monopolize critical nutrients like glucose and amino acids. This metabolic competition supports tumor growth while impairing T-cell anti-tumor responses, partly by reducing glycolytic function. Hexokinase 2 (HK2), a key enzyme in glycolysis, plays a pivotal role in maintaining T-cell functionality.</p><p><strong>Methods: </strong>To enhance T-cell function, primary human T cells were genetically engineered to overexpress HK2 alongside a tumor-specific receptor. These engineered T cells were tested <i>in vitro</i> and <i>in vivo</i> to evaluate their metabolic and therapeutic efficacy.</p><p><strong>Results: </strong>HK2-engineered T cells exhibited increased glycolytic capacity, leading to enhanced cytokine secretion, activation marker expression, and metabolic activity compared to controls. <i>In vivo</i> studies using a human tumor xenograft model demonstrated the superior therapeutic efficacy of HK2-engineered T cells, including delayed tumor growth and improved survival.</p><p><strong>Conclusion: </strong>HK2 overexpression improves T-cell metabolic fitness and functionality in hostile TMEs, offering a promising foundation for the development of next-generation immunotherapies targeting T-cell metabolism.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1477929"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779838","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":"The first WHO reference panel for Infliximab anti-drug antibodies: a step towards harmonizing therapeutic drug monitoring.","authors":"Meenu Wadhwa, Isabelle Cludts, Eleanor Atkinson, Peter Rigsby","doi":"10.3389/fimmu.2025.1550655","DOIUrl":"10.3389/fimmu.2025.1550655","url":null,"abstract":"<p><p>Immunogenicity testing for anti-drug antibodies (ADA) is mandatory for regulatory approval of a biotherapeutic and can, in some instances, continue post-licensure. Typical examples are TNF inhibitors where biotherapeutic and ADA levels are relevant in clinical decision-making for optimal patient therapy. However, challenges with non-comparability of results due to plethora of bioanalytical techniques and the lack of standardization has hindered ADA monitoring in clinical practice. Two human anti-infliximab monoclonal antibodies (A, B) with defined characteristics were therefore lyophilized and assessed for suitability as a reference panel for ADA assays in an international study. Binding assays included the simple ELISA and common electrochemiluminescence (ECL) to the rare antigen binding test and lateral flow assays. For neutralisation, competitive ligand binding and reporter-gene assays were employed. Sample testing (e.g., antibodies, sera) showed differential reactivity depending on the assay and sample. Estimates for ADA levels using in-house standards varied substantially among assays/laboratories. In contrast, using antibody A for quantitating ADA levels reduced the interlaboratory variability and provided largely consistent estimates. The degree of harmonization was dependent on the assay, sample and the laboratory. Importantly, antibody A allowed ADA detection when missed using in-house standards. Recognition of sample B varied, possibly due to its fast dissociation. Overall, the panel comprising A (coded 19/234) and B (coded 19/232) was suitable and established by the WHO Expert Committee on Biological Standardization in October 2022 as the WHO international reference panel for infliximab ADA assays. Sample A (coded 19/234) with an arbitrarily assigned unitage of 50,000IU/ampoule for binding activity and 50,000 IU/ampoule for neutralising activity is intended as a 'common standard' for assay characterization and where possible for calibration of anti-infliximab preparations to facilitate comparison and harmonization of results across infliximab ADA assays. Sample B (19/232) with its unique characteristics and variable detection but no assigned unitage is intended for assessing the suitability of the assay for detecting ADAs with fast dissociation. It is anticipated that this panel would help towards selecting and characterizing suitable assays, benchmarking of in-house standards where feasible and in harmonizing ADA assays used in clinical practice for better patient outcome globally.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550655"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779776","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":"Corrigendum: Increased neutrophil counts are associated with poor overall survival in patients with colorectal cancer: a five-year retrospective analysis.","authors":"Libia Alejandra Garcia-Flores, María Teresa Dawid De Vera, Jesus Pilo, Alejandro Rego, Gema Gomez-Casado, Isabel Arranz-Salas, Isabel Hierro Martín, Julia Alcaide, Esperanza Torres, Almudena Ortega-Gomez, Hatim Boughanem, Manuel Macias-Gonzalez","doi":"10.3389/fimmu.2025.1583828","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1583828","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1415804.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1583828"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779762","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 CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model.","authors":"Tianyin Wang, Darla Quijada, Taha Ahmedna, Jennie Ruelas Castillo, Nour Sabiha Naji, J David Peske, Petros C Karakousis, Suman Paul, Theodoros Karantanos, Styliani Karanika","doi":"10.3389/fimmu.2025.1501329","DOIUrl":"10.3389/fimmu.2025.1501329","url":null,"abstract":"<p><p>Tuberculosis (TB) remains among the leading infectious causes of death. Due to the limited number of antimicrobials in the TB drug discovery pipeline, interest has developed in host-directed approaches to improve TB treatment outcomes. C-C motif chemokine-like receptor 2 (CCRL2) is a unique seven-transmembrane domain receptor that is upregulated by inflammatory signals and mediates leucocyte migration. However, little is known about its role in TB infection. Here, we show that <i>Mycobacterium tuberculosis</i> (Mtb) infection increases CCRL2 protein expression in macrophages <i>in vitro</i> and alveolar macrophages (AMs), dendritic cells (DCs) and neutrophils in mouse lungs. To target selectively CCRL2-expressing cells <i>in vivo</i>, we developed a novel mouse anti-CCRL2 antibody-drug conjugate (ADC) linked with the cytotoxic drug SG3249. We tested its adjunctive therapeutic efficacy against TB when combined with the first-line regimen for drug-susceptible TB (isoniazid, rifampin, pyrazinamide, ethambutol; RHZE). The anti-CCRL2 ADC treatment potentiated RHZE efficacy in Mtb-infected mice and decreased gross lung inflammation. CCRL2 expression in lung DCs and AMs was lower in mice receiving anti-CCRL2 ADC treatment+RHZE compared to those receiving RHZE alone or the control group, although the total innate cell populations did not differ across treatment groups. Interestingly, neutrophils were completely absent in the anti-CCRL2 ADC treatment + RHZE group, unlike in the other treatment groups. IFN-γ+-and IL17-α+-T-cell responses, which are associated with optimal TB control, were also elevated in the anti-CCRL2 ADC treatment + RHZE group. Our findings suggest that CCRL2-targeting approaches may improve TB treatment outcomes, possibly through selective killing of Mtb-infected innate immune cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1501329"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779772","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":"Expression and significance of lncRNAs derived from PBMC in rheumatoid arthritis.","authors":"Xiaoke Yang, Zhongling Yang, Ziqiang Shuai, Mingming Zhang, Sheng-Qian Xu, Zong Wen Shuai","doi":"10.3389/fimmu.2025.1515665","DOIUrl":"10.3389/fimmu.2025.1515665","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) are gaining recognition for their critical involvement in diverse autoimmune disorders. Nevertheless, reseach investigating the role of lncRNAs in rheumatoid arthritis (RA) is relatively scarce.</p><p><strong>Methods: </strong>Comprehensive transcriptome sequencing was executed to acquire a lncRNA expression pattern in peripheral blood mononuclear cells (PBMC) of RA. Then, we confirmed the sequencing data by real-time quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>The findings showed decreased levels of LINC00494, TSP0AP1-AS1, MCM3AP-AS1 and LINC01588, increased levels of OIP5-AS1, in PBMC of RA compared to controls. ROC analysis for the five dysregulated lncRNAs demonstrated an area under curve (AUC) extending from 0.654 to 0.915, and their combination had high utility for accurate RA diagnosis (AUC = 0.920). There existed a negative relation between RF and LINC00494 expression (<i>P</i>=0.027), positive relation between anti-CCP and MCM3AP-AS1 (<i>P</i>=0.024), and negative relation between CRP and LINC01588 expression (<i>P</i>=0.020).</p><p><strong>Conclusions: </strong>Our study indicated that LINC00494, TSP0AP1-AS1, MCM3AP-AS1, LINC01588 and OIP5-AS1 in PBMC may be the biomarkers for RA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1515665"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779796","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":"Association between oxidative balance score and all-cause and cancer-specific mortality among cancer survivors.","authors":"Qingmei Gao, Xinfang Zhu, Mengke Chen, Rong Xia, Qi Zhang","doi":"10.3389/fimmu.2025.1541675","DOIUrl":"10.3389/fimmu.2025.1541675","url":null,"abstract":"<p><strong>Background: </strong>The Oxidative Balance Score (OBS) represents a novel metric for assessing systemic oxidative stress, where elevated scores reflect increased antioxidant exposure. This study aims to explore the association between OBS and all-cause and cancer-specific mortality among cancer survivors.</p><p><strong>Methods: </strong>An observational cohort study was conducted involving 4099 cancer survivors, utilizing data obtained from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999 to 2018. The endpoints were established by cross-referencing data with the National Death Index (NDI). The OBS was developed based on dietary and lifestyle factors. Cox proportional hazards regression models were employed to examine the relationship between OBS and mortality risks. Restricted cubic spline was utilized to evaluate whether OBS exhibited a nonlinear association with the risk of death. Furthermore, Kaplan-Meier survival curves were generated to assess cumulative survival differences across various OBS outcomes.</p><p><strong>Results: </strong>Over an average follow-up of 84.00 months, 1481 (26.29%) participants died, including 484 (8.9%) who died from cancer. In the fully adjusted model, multivariable Cox regression revealed that each unit increase in OBS was linked to a 1.8% decrease in all-cause mortality risk (HR 0.982, 95%CI 0.972-0.991) and a 2.6% decrease in cancer-specific mortality risk (HR 0.974, 95%CI 0.958-0.991). In the context of all-cause mortality, the risk of death was found to be significantly lower in quartiles Q2, Q3 and Q4 when compared to the OBS in quartile Q1. The hazard ratios (HRs) and 95% confidence intervals (CIs) for Q2, Q3 and Q4 were as follows: Q2 (HR 0.833, 95%CI 0.707-0.981), Q3 (HR 0.789, 95%CI 0.650-0.958) and Q4 (HR 0.699, 95%CI 0.579-0.844). Regarding cancer-specific mortality, the HRs and 95%CIs for Q2, Q3 and Q4 in comparison to Q1 were as follows: Q2 (HR 0.663, 95%CI 0.505-0.869), Q3 (HR 0.688, 95%CI 0.488-0.969) and Q4 (HR 0.595, 95%CI 0.435-0.815). Similar associations were noted when the dietary and lifestyle components of the OBS were analyzed separately.</p><p><strong>Conclusion: </strong>The findings indicate that higher levels of OBS are associated with a decrease in all-cause and cancer-specific mortality among cancer survivors. Our findings may contribute to the refinement of lifestyle intervention recommendations for this population.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1541675"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779723","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":"Evaluation of safety, immunogenicity, and efficacy of inactivated reverse-genetics-based H5N8 highly pathogenic avian influenza virus vaccine with various adjuvants via parenteral and mucosal routes in chickens.","authors":"Kairat Tabynov, Aidana Kuanyshbek, Leila Yelchibayeva, Kuantay Zharmambet, Zauresh Zhumadilova, Gleb Fomin, Nikolai Petrovsky, Olaitan C Shekoni, Gourapura J Renukaradhya, Kaissar Tabynov","doi":"10.3389/fimmu.2025.1539492","DOIUrl":"10.3389/fimmu.2025.1539492","url":null,"abstract":"<p><strong>Background: </strong>Highly pathogenic H5Nx avian influenza (HPAI) poses a significant threat to poultry health globally, necessitating the development of effective vaccination strategies.</p><p><strong>Methods: </strong>This study assessed the immunogenicity and efficacy of a reverse-genetics-derived, Differentiating Infected from Vaccinated Animals (DIVA)-compatible inactivated H5N8 vaccine based on the IDCDC-RG71A strain. The vaccine was formulated with different adjuvants, including Montanide ISA 78 VG, ISA 71 R VG, GEL P PR, and mannose-conjugated chitosan nanoparticles, and administered via either the subcutaneous (SC) or intranasal (IN) route. To evaluate safety, the vaccine was tested in specific antibody negative (SAN) chickens, showing no adverse effects. Immunogenicity was assessed by measuring hemagglutination inhibition (HI) antibody titers, antigen-specific IgA and IgY levels, and CD4+ and CD8+ T cell proliferation. Vaccine efficacy was determined through a challenge study using a field isolate of H5N1.</p><p><strong>Results: </strong>This showed that a single SC dose of vaccine containing ISA 78 VG or ISA 71 R VG provided the best efficacy against infection, with high survival rates, control of abnormally high temperature incidence, reduced virus shedding, and reduced lung and liver lesions. The ISA 78 VG-adjuvanted SC vaccine induced the highest HI titers and CD4+ T cell proliferation, while ISA 71 R VG and GEL P PR elicited the strongest IgY responses. In contrast, IN formulations induced IgA in the lungs and trachea however, even after two doses, failed to generate high HI titers and provided poor, if any, protection against infection. This highlights the superior efficacy of the SC over the IN route of vaccination for reducing H5N1 viral shedding.</p><p><strong>Conclusion: </strong>These results underscore the importance of both the adjuvants and delivery route to maximize HPAI vaccine efficacy. This presented system could thereby be used to develop potent and DIVA-compatible vaccines to enhance biosecurity and disease management in regions affected by endemic HPAI.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1539492"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779793","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":"Patient-reported outcomes with subcutaneous immunoglobulin in secondary immunodeficiency.","authors":"Juthaporn Cowan, Il-Kang Na, André Gladiator, Marta Kamieniak, S Shahzad Mustafa","doi":"10.3389/fimmu.2025.1528414","DOIUrl":"10.3389/fimmu.2025.1528414","url":null,"abstract":"<p><p>Subcutaneous (SCIG) and intravenous immunoglobulin (IVIG) replacement are both used to prevent infections in patients with secondary immunodeficiency (SID). Compared with IVIG, SCIG has fewer systemic side effects and, additionally, facilitates home-based treatment. Shared decision-making practice should include discussion of aspects such as patient preference as well as the associated risks and benefits of treatment. We review the available evidence for the use of SCIG treatment in patients with SID, focusing on patient-reported outcomes (PROs). In most studies, there were improvements to health-related quality of life with SCIG treatment, compared with before initiating SCIG without prior IVIG treatment, or after switching to SCIG from IVIG treatment, or a no-SCIG/IVIG cohort. Treatment satisfaction with SCIG was similar between patients with SID and primary immunodeficiency disease. Patient preference and perception assessments highlighted the benefits of SCIG compared with IVIG, such as ease of use and administration, convenience, and time-effectiveness. In addition, many patients self-administered SCIG at home. Such aspects may be of specific benefit to patients with SID and hematological malignancy by reducing the risk of infection exposure in clinical settings. PRO data may be useful during shared decision-making discussions with patients with SID.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1528414"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779419","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":"Current understanding on inferior quality of liver grafts by donation after circulatory death based on multi-omics data.","authors":"Yifeng Zhou, Ting Que, Lu Yu, Shuping Que, Jun Xu, Zhengtao Liu","doi":"10.3389/fimmu.2025.1548735","DOIUrl":"10.3389/fimmu.2025.1548735","url":null,"abstract":"<p><p>Given the inevitable hypoxia and reperfusion injury that occur in organs donated after circulatory death (DCD), the quality and function of these organs are significantly compromised, greatly limiting their application in clinical organ transplantation. Recently, the advancement of functional omics technologies has enabled us to deeply analyze the mechanisms underlying DCD donor organ damage from multiple perspectives. This review systematically integrates the studies from transcriptomics, proteomics, and metabolomics to reveal the key biological mechanisms associated with the declines in DCD donor organ quality, including oxidative stress, inflammatory responses, cell death pathways, and metabolic disturbances. Additionally, we summarized emerging therapeutic strategies based on findings from omics perspectives, offering new possibilities to improve the quality of DCD organ for better transplant prognosis. Finally, we discussed the challenges in current research and future directions to provide scientific evidence for clinical practice and promote the application of DCD donors in organ transplantation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1548735"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779769","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":"Autoantibodies to apolipoprotein A-I in hepatitis C virus infection: a role in disease progression?","authors":"Simon H Bridge, Sabrina Pagano, John K Lodge, Isaac T Shawa, Paula Marin-Crespo, Matthew E Cramp, David A Sheridan, Simon D Taylor-Robinson, Nicolas Vuilleumier, R Dermot G Neely, Margaret F Bassendine","doi":"10.3389/fimmu.2025.1461041","DOIUrl":"10.3389/fimmu.2025.1461041","url":null,"abstract":"<p><strong>Background: </strong>Chronic HCV (CHC) infection is associated with autoimmunity. IgG autoantibodies to apolipoprotein A-I (AAA-I) predict all-cause mortality. We evaluated AAA-I in CHC patients and in those who were not viraemic, either because of spontaneous resolution (SR) of infection or HCV clearance following sustained virological response (SVR) after interferon therapy. We limited the study to HCV genotypes 1 and 3, the dominant HCV genotypes circulating in the UK.</p><p><strong>Methods: </strong>Serum samples from 126 CHC patients and 114 nonviraemic individuals (25 SR and 89 SVR) were assayed for AAA-I and lipoproteins. AUC was calculated for AAA-I and HDL-related parameters and used to predict cirrhosis. Fibronectin (FN) and FN-mRNA were measured in human hepatic stellate cells (LX-2) in the presence or absence of AAA-I.</p><p><strong>Results: </strong>AAA-I was found in 47% of patients with CHC, 37% of SVR patients, and 16% of SR individuals (CHC vs. SR, <i>p</i> = 0.004). AAA-I levels in CHC patients were higher in those with cirrhosis (<i>p</i> = 0.0003). The AUC for AAA-I, apoA-I, and HDL-C in predicting cirrhosis was 0.72 (<i>p</i> < 0.001), 0.65 (<i>p</i> = 0.01), and 0.64 (<i>p</i> = 0.02). After 48 h in the presence of AAA-I, LX-2 cells showed an 80% increase in FN-mRNA compared to the LX-2/IgG control (<i>p</i> = 0.028) and higher levels of FN (<i>p</i> = 0.0016).</p><p><strong>Conclusions: </strong>CHC is often associated with AAA-I, and these can persist after SVR. AAA-I is a robust predictor of cirrhosis in CHC infection. LX-2 cells exposed to AAA-I showed increased FN. Further studies are warranted to define the role of AAA-I in promoting not only viral persistence but also fibrosis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1461041"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779743","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}