Immunology最新文献

{"title":"Intestinal Butyrate Ameliorates Rheumatoid Arthritis Through Promoting the Expression of Cortistatin in Ileum via HDAC3—Vitamin D Receptor Pathway","authors":"Minghui Liao,&nbsp;Yanrong Zhu,&nbsp;Qi Cui,&nbsp;Mengfan Yue,&nbsp;Jialin Li,&nbsp;Lei Gao,&nbsp;Yue He,&nbsp;Yilei Guo,&nbsp;Wenjie Zhang,&nbsp;Zhifeng Wei,&nbsp;Yufeng Xia,&nbsp;Yue Dai","doi":"10.1111/imm.13939","DOIUrl":"10.1111/imm.13939","url":null,"abstract":"<div>\u0000 \u0000 <p>Butyrate, administered orally or via drinking water, can effectively ameliorate experimental rheumatoid arthritis (RA) in mice despite its limited bioavailability. The discrepancy urges us to explore the involvement and role of intestinal anti-RA factors in the action of butyrate. In this study, we found that substituting drinking water with butyrate (75 mM) could promote the expression of cortistatin (CST) in the ileal epithelium of mice with collagen-induced arthritis (CIA), but butyrate did not alter the expression of other anti-RA neuropeptides in the intestine and the expression of CST in the spleen and brain. The anti-RA efficacy of butyrate was remarkably reduced following adeno-associated virus (AAV)-mediated knockdown of CST. Transcription factor screening revealed that butyrate upregulated CST expression via the vitamin D receptor (VDR). Notably, butyrate-induced VDR and CST expression in intestinal epithelial cells was diminished by α-cyano-4-hydroxycinnamic acid (CHC) rather than siRNA targeting G protein-coupled receptors (GPCRs), suggesting that butyrate functions through an intracellular pathway. Furthermore, butyrate significantly reduced HDAC activity in intestinal epithelial cells and HDAC3 plasmid transfection attenuated the upregulation of butyrate against VDR and CST expression. Chromatin immunoprecipitation assay showed that butyrate selectively enhanced histone acetylation in the P3 and P4 regions of the VDR promoter. In summary, intestinal butyrate exerts an anti-RA effect through selectively promoting the expression of CST in ileal epithelial cells via the HDAC3-VDR pathway.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"373-390"},"PeriodicalIF":4.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Impact of Outer Membrane Protein, OmpA, From S. Typhimurium on Aberrant AID Expression and IgM to IgA Class Switching in Human B-Cells","authors":"Rahul Chaudhari,&nbsp;Mallar Dasgupta,&nbsp;Prashant Kodgire","doi":"10.1111/imm.13938","DOIUrl":"10.1111/imm.13938","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Salmonella enterica</i> serovar Typhimurium is a Gram-negative bacterium that causes gastrointestinal infection and poses significant public health risks worldwide. This study aims to explore how <i>S</i>. Typhimurium manipulates B-cell function through outer membrane protein A (OmpA). We investigate the effect of OmpA on Raji human B-cells, leading to the induction of activation-induced cytidine deaminase (AID) protein, which plays an important role in generating antibody diversity in B-cells, via initiating the process of somatic hypermutation (SHM) and class switch recombination (CSR). Our key findings demonstrate that OmpA is crucial for inducing aberrant AID expression in B-cells, leading to increased CSR. Interestingly, the increased AID expression was likely due to overexpression of cMYC, an activator for AID expression. Not only was the expression of cMYC elevated, but its occupancy on the <i>aicda</i> locus was raised. Furthermore, increased AID expression induced CSR events, specifically switching to IgA. In summary, our study suggests that OmpA plays a potential role in modulating B-cell regulation and controlling the adaptive immune system. These functional attributes of OmpA implicate its potential as a therapeutic target for combating <i>S.</i> Typhimurium pathogenesis.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"359-372"},"PeriodicalIF":4.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Novel Multi-Epitope Vaccine Against Streptococcus anginosus Infection via Reverse Vaccinology Approach","authors":"Linglan Xu,&nbsp;Nan Xie,&nbsp;Yiqing Liu,&nbsp;Hongmei Tang,&nbsp;Tian Li,&nbsp;Jiaofeng Peng,&nbsp;Ranhui Li","doi":"10.1111/imm.13936","DOIUrl":"10.1111/imm.13936","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Streptococcus anginosus</i> is an opportunistic pathogen known for its capability to cause a broad range of infections, posing a significant and growing global health concern. Alongside enhancing diagnostic capabilities and bolstering public health initiatives, developing a safe and effective vaccine represents a promising strategy to tackle this health challenge. In this paper, we employed an array of bioinformatics tools to engineer a subunit vaccine that exhibits high immunogenicity against <i>S. anginosus</i>. After constructing the multi-epitope vaccine, we subsequently predicted its secondary and tertiary protein structures. After refining and validating the modelled structure, we utilised advanced computational approaches, including molecular docking and dynamic simulations, to evaluate the binding affinity, compatibility, and stability of the vaccine–adjuvant complexes. Eventually, in silico cloning was conducted to optimise protein expression and production. The multi-epitope subunit vaccine we developed showed properties in antigenicity and immunity theoretically. The computational study revealed that this vaccine demonstrates significant efficacy against <i>S. anginosus</i>.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"339-358"},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-Induced Metabolic Priming Exacerbates SARS-CoV-2 Inflammation","authors":"Gustavo Gastão Davanzo,&nbsp;Bianca Gazieri Castelucci,&nbsp;Gabriela Fabiano de Souza,&nbsp;Stéfanie Primon Muraro,&nbsp;Larissa Menezes dos Reis,&nbsp;Isabella Bonilha de Oliveira,&nbsp;José Luís Fachi,&nbsp;João Victor Virgilio-da-Silva,&nbsp;Marcelo Rodrigues Berçot,&nbsp;Mariane Font Fernandes,&nbsp;Sarah de Oliveira,&nbsp;Nathalia Vitoria Pereira Araujo,&nbsp;Guilherme Ribeiro,&nbsp;Gisele de Castro,&nbsp;Webster Leonardo Guimarães Costa,&nbsp;Adriana Leandra Santoro,&nbsp;Gabriela Flavia Rodrigues-Luiz,&nbsp;Helison Rafael P. do Carmo,&nbsp;Ikaro Breder,&nbsp;Marcelo A. Mori,&nbsp;Alessandro S. Farias,&nbsp;Daniel Martins-de-Souza,&nbsp;Joseph W. Guarnieri,&nbsp;Douglas C. Wallace,&nbsp;Marco Aurélio Ramirez Vinolo,&nbsp;José Luiz Proença-Módena,&nbsp;Afshin Beheshti,&nbsp;Andrei C. Sposito,&nbsp;Pedro M. Moraes-Vieira","doi":"10.1111/imm.13934","DOIUrl":"10.1111/imm.13934","url":null,"abstract":"<p>Despite the early recognition that individuals living with obesity are more prone to develop adverse outcomes during COVID-19, the mechanisms underlying these conditions are still unclear. During obesity, an accumulation of free fatty acids (FFAs) in the circulation promotes low-grade inflammation. Here, we show that FFAs induce epigenetic reprogramming of monocytes, exacerbating their inflammatory profile after SARS-CoV-2 infection, a mechanism named metabolic-primed immunity. Monocytes from people with obesity or primed with palmitate, a central component of circulating FFAs, presented elevated viral load and higher gene expression of IL-6. Palmitate-primed monocytes upregulate fatty acid oxidation and FFAs entry into the mitochondria. FFA-derived acetyl-CoA is then converted into citrate, exiting the mitochondria and is used to support H3K18 histone acetylation, which regulates IL-6 accessibility. Ingestion of palm oil by lean and healthy individuals increased circulating FFAs levels and was sufficient to exacerbate the inflammatory profile of monocytes upon SARS-CoV-2 infection. Our findings demonstrate that obesity-derived FFAs induce the metabolic priming of monocytes, which exacerbates the inflammatory response observed in people with severe COVID-19.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"323-338"},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human γδ T Cell Function Is Impaired Upon Mevalonate Pathway Inhibition","authors":"Tsz Kin Suen,&nbsp;Burcu Al,&nbsp;Thomas Ulas,&nbsp;Nico Reusch,&nbsp;Harsh Bahrar,&nbsp;Siroon Bekkering,&nbsp;Jaydeep Bhat,&nbsp;Dieter Kabelitz,&nbsp;Joachim L. Schultze,&nbsp;Frank L. van de Veerdonk,&nbsp;Jeanine Roeters van Lennep,&nbsp;Niels P. Riksen,&nbsp;Leo A. B. Joosten,&nbsp;Mihai G. Netea,&nbsp;Katarzyna Placek","doi":"10.1111/imm.13931","DOIUrl":"10.1111/imm.13931","url":null,"abstract":"<p>Vδ2 T cells, a predominant human peripheral γδ T cell population, are a promising candidate for the development of immunotherapies against cancer and infected cells. Aminobisphosphonate drugs, such as zoledronate, are commonly used to expand Vδ2 T cells. Yet, such in vitro generated cells have limited efficacy in the clinic. We found that despite inducing excessive proliferation of Vδ2 T cells, zoledronate impaired their effector function and caused the upregulation of the inhibitory receptor TIM3. This effect was due to the inhibition of mevalonate metabolism and dysregulation of downstream biological processes such as protein prenylation and intracellular signalling. In vitro and in vivo inhibition of mevalonate metabolism with zoledronate, statins, and 6-fluoromevalonate, as well as genetic deficiency of the mevalonate kinase, all resulted in compromised cytokine and cytotoxic molecule production by Vδ2 T cells. Impaired Vδ2 T cell function was accompanied by transcriptome and kinome changes. Our findings reveal the importance of mevalonate metabolism for the proper functioning of Vδ2 T cells. This observation provides important considerations for improving their therapeutic use and has repercussions for patients with statin or aminobisphosphonate treatments.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"300-322"},"PeriodicalIF":4.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical C3 Inhibition With AMY-101 Reveals Novel Insights Into IL-8-Driven Inflammation in COVID-19","authors":"Christina Antoniadou,&nbsp;Anastasia-Maria Natsi,&nbsp;Dimitrios C. Mastellos,&nbsp;Evangelos Papadimitriou,&nbsp;Efstratios Gavriilidis,&nbsp;Victoria Tsironidou,&nbsp;Vasileios Papadopoulos,&nbsp;Evgenios Eftalitsidis,&nbsp;Μaria Κoffa,&nbsp;Markus Huber-Lang,&nbsp;Antonio M. Risitano,&nbsp;Despina Yancopoulou,&nbsp;Georgios Germanidis,&nbsp;Konstantinos Ritis,&nbsp;John D. Lambris,&nbsp;Panagiotis Skendros","doi":"10.1111/imm.13930","DOIUrl":"10.1111/imm.13930","url":null,"abstract":"&lt;p&gt;Complement overactivation drives the hyperinflammatory state of severe COVID-19, fueling a cycle of neutrophil-driven immunothrombosis, excessive cytokine release and endothelial injury [&lt;span&gt;1-3&lt;/span&gt;]. In this context, neutrophils migrate to the lungs, releasing neutrophil extracellular traps (NETs) that interact with lung fibroblasts, which in turn amplify thromboinflammatory and immunofibrotic responses, further impacting disease progression [&lt;span&gt;1, 4-7&lt;/span&gt;]. Interleukin-8 (IL-8) is a major neutrophil chemoattractant expressed by various cells, including neutrophils. Previous data have indicated that neutrophil-derived systemic and pulmonary IL-8 is overexpressed in COVID-19, aggravating disease immunopathology and prognosis [&lt;span&gt;7, 8&lt;/span&gt;]. However, the role of complement in IL-8-associated disease pathology has yet to be clarified.&lt;/p&gt;&lt;p&gt;Considering and expanding upon the above findings, here we provide a novel mechanism that links complement C3 activation with IL-8-driven inflammation during neutrophil-lung fibroblast interaction in severe COVID-19, by leveraging clinical data and samples from the ITHACA study, the only randomised, placebo-controlled clinical trial of the compstatin-based C3 therapeutic AMY-101 in COVID-19-associated acute respiratory distress syndrome (ARDS) [&lt;span&gt;9&lt;/span&gt;]. AMY-101 administration resulted in complete and sustained inhibition of C3 activation in all responders, alongside a reduction in thromboinflammatory markers associated with disease progression [&lt;span&gt;9&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We analysed all 26 survivors of COVID-19-related ARDS, who had received either AMY-101 (5 mg/kg; &lt;i&gt;n&lt;/i&gt; = 13) or placebo (&lt;i&gt;n&lt;/i&gt; = 13), in addition to standard-of-care therapy, which included dexamethasone and low molecular weight heparin. To evaluate the in vivo effect of C3 inhibition on IL-8 expression, we measured IL-8 plasma levels in both study groups at baseline (D0) and at Day 7 post-treatment (D7). IL-8 plasma levels were found to be significantly reduced in the AMY-101-treated patients at D7 compared to D0. In contrast, this effect was not observed in the respective samples of placebo-treated patients (Figure 1A). Moreover, the key markers of complement activation, C3a and sC5b-9, including both D0 and D7 values, were found to be well correlated with the corresponding IL-8 levels (Figure 1B), suggesting a pathomechanistic role of complement activation in IL-8-associated inflammation during severe COVID-19.&lt;/p&gt;&lt;p&gt;Prompted by the above findings, we sought to investigate the potential cellular sources of IL-8 that may be modulated by C3 inhibition with AMY-101. Lung fibroblasts and neutrophils are considered key components of the maladaptive inflammatory response, leading to lung tissue damage and impaired respiratory function in COVID-19-associated ARDS [&lt;span&gt;4, 6, 8, 10&lt;/span&gt;]. Incubation of healthy lung fibroblasts with D7 AMY-101 plasma yielded significantly lower IL-8 expression compared to the respective","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"288-291"},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13930","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Contribution of Complement System in Multiple Sclerosis: Mechanisms and Therapeutic Potentials","authors":"Runjing Cao,&nbsp;Li-Wen Zhu,&nbsp;Bo Chen,&nbsp;Huadong Wu,&nbsp;Yifan Cheng,&nbsp;Shunyuan Guo","doi":"10.1111/imm.13929","DOIUrl":"10.1111/imm.13929","url":null,"abstract":"<p>The complement system has been described as playing key roles in both innate and adaptive immune responses. Multiple sclerosis (MS) is an autoimmune disease characterised by the destruction of myelinated axons in the central nervous system (CNS). In this review, we will discuss the possible role of the complement system in MS. Complement components have been found to be highly expressed in post-mortem brains and in blood and cerebrospinal fluid samples of MS patients. Though the use of knock-out mouse models, the specific roles of complement components have been further investigated. According to these studies, complement components have been found to play controversial roles in the pathogenesis of MS. We will discuss the roles of classical and alternative pathways, as well as the lectin pathway, of the complement system in MS. Anaphylatoxins including C3a and C5a were also found to contribute to the pathology of MS. In addition, studies regarding the complement components in blood and cerebrospinal fluid are presented, which may be useful for the prediction and assessment of MS as biomarkers. Overall, this review summarises the importance of the complement system's involvement in the pathology of MS, which may guide future therapeutic approaches to MS and provide potential biomarkers for MS diagnosis and prognosis.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"263-279"},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13929","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B Cells as a Host of Persistent Salmonella Typhimurium","authors":"Alonso D. Cruz-Cruz,&nbsp;Jocelyn C. Pérez-Lara,&nbsp;Diana Z. Velázquez,&nbsp;Gabriela Hernández-Galicia,&nbsp;Vianney Ortiz-Navarrete","doi":"10.1111/imm.13928","DOIUrl":"10.1111/imm.13928","url":null,"abstract":"<p><i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>. Tm) can colonise different intracellular niches, either actively dividing or remaining dormant to persist. Bacterial persisters are phenotypic variants that temporarily enter a nonreplicative state. This allows them to evade host cell defences and antibiotics, leading to chronic infections. We previously reported that during chronic periods, <i>Salmonella</i> remains within B cells in the bone marrow and spleen. However, the dynamics of <i>Salmonella</i> replication and the formation of antibiotic tolerance in infected B cells have not been studied. Here we show that B cells are a favourable reservoir for bacterial persistence. In vitro and in vivo experiments identified non-replicating, persistent <i>Salmonella</i> subsets in splenic B cells. These non-replicative <i>Salmonella</i> are tolerant to antibiotics (cefotaxime and ciprofloxacin), while replicative bacteria remain susceptible. Infected mice demonstrated viable, nonreplicative <i>Salmonella</i> in spleen B cells, maintaining antibiotic tolerance. Although acid intravacuolar pH and SPI-2 regulators (SsrA/SsrB) are not necessary for <i>Salmonella</i> persistence in B cells, the SehA/B and RelE/B toxin-antitoxin system facilitates the formation of the persistent phenotype in <i>Salmonella</i>. Overall, we show that B cells are a reservoir for nonreplicating, antibiotic-tolerant <i>Salmonella</i>.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 3","pages":"292-299"},"PeriodicalIF":4.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAA1 as a Potential Early Diagnostic Biomarker for Sepsis Through Integrated Proteomics and Metabolomics.","authors":"Mengyao Yuan, Pengfei Huang, Yuhan Liu, Lifeng Shen, Chuanchuan Nan, Yuchen Song, Yu Xiao, Yuxin Zhang, Yuxin Zhou, Yu Xin, Yanqi Liu, Hongxu Li, Yinghao Luo, Qianqian Zhang, Xinran Wang, Dawei Wang, Jiannan Zhang, Likun Zhang, Mingyan Zhao, Kaijiang Yu, Changsong Wang","doi":"10.1111/imm.13925","DOIUrl":"https://doi.org/10.1111/imm.13925","url":null,"abstract":"<p><p>Sepsis is characterised by fatal organ dysfunction resulting from a dysfunctional host response to infection, imposing a substantial economic burden on families and society. Therefore, identifying biomarkers for early sepsis diagnosis and improving patient prognosis are critical. This study recruited 59 sepsis patients and 35 healthy volunteers from the Department of Critical Care Medicine at Harbin Medical University Affiliated First Hospital between March and December 2021. Through a combination of non-targeted and targeted proteomics and metabolomics sequencing, along with various analytical methods, we initially identified and validated serum amyloid A1 (SAA1) as a diagnostic biomarker for sepsis. Our study found that SAA1 was significantly elevated in the sepsis group, demonstrating its diagnostic value for sepsis (AUC: 0.95, 95% CI: 0.88-1). Additionally, a positive correlation was observed between SAA1 and disease severity, as indicated by the Sequential Organ Failure Assessment (SOFA) score (R = 0.51, p = 0.004) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score (R = 0.52, p = 0.003). This study suggests that SAA1 is a potentially effective and reliable marker for diagnosing sepsis and predicting its severity.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycobacterium avium Subsp. paratuberculosis and Human Endogenous Retrovirus in Italian Patients With Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS).","authors":"Stefano Ruberto, Alfredo Santovito, Gian P Caviglia, Marta Noli, Davide Cossu, Davide G Ribaldone, Demis Pitoni, Simona Frara, Elisa Tribocco, Chiara Rosso, Marta Guriglia, Ilaria Cossu, Pier A Tovo, Massimiliano Bergallo, Leonardo A Sechi","doi":"10.1111/imm.13923","DOIUrl":"https://doi.org/10.1111/imm.13923","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD) and irritable bowel syndrome (IBS) are distinct gastrointestinal disorders. Mycobacterium avium subspecies paratuberculosis (MAP) is implicated in IBD pathogenesis, while the roles of human endogenous retroviruses (HERVs) are under investigation. We aimed (a) to investigate whether the levels of humoral response to MAP-3865c, HERV-K envelope and HERV-W envelope against the epitopes in IBD/IBS patients; (b) to determine the frequency of micronuclei in IBD patients and (c) to evaluate the possible correlation between genomic damage and humoral response. This study investigates antibody titres against MAP 3865c, HERV-K env and HERV-W env in plasma from 102 IBD, 20 IBS patients and 92 healthy controls (HCs). Micronuclei (MNi) frequency in IBD patients is assessed, correlating with humoral responses and patient genotype profiles. IBD patients exhibited elevated antibody responses to MAP 3865c, with those carrying the GA genotype for TNF-α showing higher anti-MAP 3865c IgG levels. A significant positive correlation was observed between MNi frequency and the humoral response against MAP 3865c in IBD patients. Higher antibody responses to HERV-K env were detected in both IBD and IBS patients compared to HCs, with significant positive correlations found between MAP 3865c and HERV-K env peptide responses in IBD patients. HERV-W env antibody levels were higher in IBS patients than in HCs. Our findings highlight the association between UC and CD and immune responses targeting MAP and HERV-Kenv. Specific genetic profiles may exacerbate inflammation, potentially amplifying genetic damage observed in IBD patients, as indicated by MNi frequencies.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}