{"title":"Tissue resident memory B cells mediate protective immunity to respiratory pathogens in the airways","authors":"Ivy M. Akehurst, Louisa K. James","doi":"10.1016/j.imlet.2025.107091","DOIUrl":"10.1016/j.imlet.2025.107091","url":null,"abstract":"<div><div>Respiratory pathogens pose a significant risk to public health and are responsible for burdening health care by causing worldwide morbidity and mortality. The immune environment in the airway is critical for protection from respiratory pathogens and comprises several specialist subsets of resident lymphocytes and myeloid cells. Tissue resident-memory B cells (B<sub>RM</sub>) are a subset of memory B cell which reside in mucosal tissues, including the airways. Although, B<sub>RM</sub> have only recently been characterised, they have a crucial role in generating robust and localised immune responses to respiratory infections, particularly secondary responses, by rapidly differentiating into antibody-secreting cells. A greater understanding of their role in protecting the airways from respiratory pathogens will enable the development of immunisation strategies against respiratory disease. This mini-review aims to summarise the current knowledge of B<sub>RM</sub> and highlight areas for future research.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107091"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coordination of cellular responses to SARS-CoV-2 during severe COVID-19 illness","authors":"Assia Samri , Raphael Lhote , Alice Rousseau , Véronique Morin , Nadine Tarantino , Stéphane Marot , Aude Jary , Delphine Sterlin , Anne-Geneviève Marcelin , Zahir Amoura , Guy Gorochov , Vincent Vieillard , Amélie Guihot","doi":"10.1016/j.imlet.2025.107090","DOIUrl":"10.1016/j.imlet.2025.107090","url":null,"abstract":"<div><div>The early cellular and humoral immune responses to SARS-CoV-2 result in a wide range of COVID-19 disease severity. Here we conducted an observational study of these three arms of the immune responses (T, B and NK) to SARS-CoV-2 in 17 patients hospitalized for severe COVID-19 at median of 31 days after first symptoms. We found that the main T cell response was directed against two specific regions of the spike viral protein, called B and E, which are inversely correlated with the expression of the KIR2DL1 inhibitory receptor on NK cells (p = 0.03, and p = 0.0001 respectively). Furthermore, expression of the inhibitory receptor ILT2 on NK cells was only correlated with T cell responses against the specific E region (p = 0.02), suggesting that HLA-G may play a role in the extinction of the NK response to the T cell response. Moreover, the antibody response was mainly directed against the nucleocapsid, whereas the antibody neutralizing response was inversely correlated with the cellular response to spike (p < 0.003). Taken together these data suggest a strong coordination between the innate and adaptive immune responses during the acute phase of infection, which could reflect the further resolution of COVID-19 patients with severe disease.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107090"},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune checkpoint molecules as predictive markers of COVID-19 severity: A comprehensive univariable and multivariable analysis","authors":"Adam Majchrzak , Paulina Niedźwiedzka-Rystwej , Dominika Bębnowska , Bogusz Aksak-Wąs , Malwina Karasińska-Cieślak , Danuta Cembrowska-Lech , Karolina Skonieczna-Żydecka , Kaja Mielczak , Anna Urbańska , Rafał Hrynkiewicz , Filip Lewandowski , Miłosz Parczewski","doi":"10.1016/j.imlet.2025.107089","DOIUrl":"10.1016/j.imlet.2025.107089","url":null,"abstract":"<div><div>Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107089"},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishing a system to identify correlations among immune system components for exploring alternative pathways for immune information transfer","authors":"Yaron Ilan","doi":"10.1016/j.imlet.2025.107085","DOIUrl":"10.1016/j.imlet.2025.107085","url":null,"abstract":"<div><h3>Introduction</h3><div>The classic immune system information transfer occurs through direct cell-to-cell contact and the secretion of mediators. However, certain immune phenomena suggest alternative pathways exist between immune components that operate independently of these conventional mechanisms.</div></div><div><h3>Methods</h3><div>We used 24 male C57Bl/6 J mice, divided into six groups, to establish a system for testing alternative immune information transfer pathways. Two triggers—splenectomy and 24-hour fasting—were applied in various combinations. Splenocytes were prepared from operated mice and placed in sterile tubes within cages of different treatment groups. Ex vivo lymphocyte responses were measured using fluorescence-activated cell sorting (FACS) for cell epitope expression (CD4, CD8, CD25, Foxp3) and enzyme-linked immunosorbent assay (ELISA) for cytokine secretion (IFN-γ, TNF-α, IL-10, TGF-β).</div></div><div><h3>Results</h3><div>Significant changes were observed in CD25 and CD8+CD25 expression, as well as in IL-10 secretion, following the application of the triggers. The system exhibited inherent variability with trends toward altered immune responses in isolated splenocytes that had no direct contact with the trigger-exposed animals. Non-parametric analysis indicates a trend for these markers, even though there is significant variability within the groups..</div></div><div><h3>Conclusions</h3><div>The data suggest a system where correlations between immune components may occur through alternative pathways, indicating the possibility of non-conventional information transfer mechanisms in the immune system that require further investigation.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107085"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of islet antigen-specific autoreactive T cells from Japanese patients with slowly progressive insulin-dependent diabetes mellitus.","authors":"Noriyuki Kitagawa, Nobuko Kitagawa, Ayaka Kobayashi, Takuro Okamura, Masahide Hamaguchi, Michiaki Fukui","doi":"10.1016/j.imlet.2025.107084","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107084","url":null,"abstract":"<p><p>Pancreatic islet antigen-specific autoreactive T cells are involved in inflammation in slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Pancreatic islet antigens, such as glutamic acid decarboxylase 65 (GAD), insulinoma-associated protein 2 (IA-2), and insulin, are associated with SPIDDM. However, the association between pancreatic islet antigen-specific T cells and SPIDDM incidence remains unclear. We aimed to identified the characteristics of pancreatic islet antigen autoreactive T cells in Japanese patients with SPIDDM. Peripheral blood mononuclear cells were obtained from Japanese patients with type 1 diabetes mellitus (T1DM) enrolled in our diabetic cohort study. An ex vivo cytokine assay using overlapping peptides of GAD, IA-2, and insulin was performed. The production of tumor necrosis factor-alpha (TNF-α) by CD4⁺ T cells and the fractions of TNF-α⁺ CD4⁺ T cell fractions were measured by fluorescence-activated cell sorting. The %parent of TNF-α⁺ CD4⁺ T cells and the effector memory TNF-α⁺ CD4⁺ T cells increased after stimulation with overlapping GAD and IA-2 peptides. The response to overlapping peptides was varied among individual SPIDDM case. Response to overlapping peptides of GAD, IA-2, and insulin were observed in each group of T1DM. Islet antigen-specific autoreactive TNF-α⁺ CD4<sup>+</sup> T cells from Japanese patients with SPIDDM were activated by overlapping GAD and IA-2 peptides.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107084"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ellen Kong , Alex Cucco , Adnan Custovic , Sara Fontanella
{"title":"Machine learning in allergy research: A bibliometric review","authors":"Ellen Kong , Alex Cucco , Adnan Custovic , Sara Fontanella","doi":"10.1016/j.imlet.2025.107088","DOIUrl":"10.1016/j.imlet.2025.107088","url":null,"abstract":"<div><div>The emergence of big data and analytic approaches initiated research efforts to characterise different subtypes of allergic diseases, including tracking disease progression and identifying patterns that may offer insight into their development and progression. Triangulation from different data sources and study types may help to elucidate the directionality of relationships between variables at a very individual level by modelling the complex interdependencies between multiple dimensions (e.g., genome, transcriptome, epigenome, microbiome, and metabolome), thereby moving away from associative to a more causal analysis. To ascertain the role of machine learning in allergy research, we conducted a comprehensive systematic review of the current literature. The findings highlight and underscore the potential of using AI/ML approaches in advancing our understanding of allergic diseases, which ultimately enhances patient care through improved prevention, diagnosis, and management strategies. It is important to emphasise that there is no single ‘best’ analytical method, highlighting the importance of cross-disciplinary collaborations. A team science approach is crucial for ensuring the application of appropriate methodologies tailored to the research question at hand and that context-specific interpretations are being made, supported by critical appraisal from both the front- (e.g., clinicians) and back-end (e.g., analysts) of research processes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107088"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vitro analysis of azithromycin’s effect on J774 murine macrophages challenged with Aspergillus fumigatus","authors":"Ivy Antwi, Jarrod R. Fortwendel, Theodore J. Cory","doi":"10.1016/j.imlet.2025.107087","DOIUrl":"10.1016/j.imlet.2025.107087","url":null,"abstract":"<div><h3>Background</h3><div>Patients with chronic lung diseases often suffer from pulmonary aspergillosis, caused by <em>Aspergillus fumigatus</em> (AF). Alveolar macrophages play a key role in the initial immune response to AF. Azithromycin (AZM), commonly known for its immunomodulatory properties in reducing exacerbations and improving lung function, has mixed effects on the development of aspergillosis. While some studies suggest AZM aids AF-colonized patients, others indicate increased rates of AF colonization.</div></div><div><h3>Objective</h3><div>Given AZM's positive impact on host response to other pathogens, we hypothesized that it would improve immune responses to AF by modulating macrophage function. We investigated the in vitro effect of AZM on J774 murine macrophage response to <em>Aspergillus fumigatus.</em></div></div><div><h3>Method</h3><div>The murine macrophage cell line J774 was polarized into distinct phenotypes: (1) classical M1 macrophages, generated using interferon-gamma (IFN-γ) and lipopolysaccharide (LPS); (2) azithromycin-treated M1 macrophages (hereafter referred to as M1A macrophages), generated by treating M1 cells with azithromycin in addition to IFN-γ and LPS; and (3) alternatively activated M2 macrophages, generated using interleukin-4 (IL-4), interleukin-13 (IL-13), and LPS. These polarized macrophages were then analyzed for cytokine production, fungal killing capacity, and reactive oxygen species (ROS) generation.</div></div><div><h3>Results</h3><div>We observed a shift in macrophage phenotype toward an anti-inflammatory-like profile in the AZM-treated group, characterized by an increased fungal killing compared to both M1- and M2-polarized groups. This was accompanied by a reduction in interleukin-6 (IL-6) cytokine production, an increase in arginase activity, without any significant change in ROS generation. Further assays confirmed that the observed increase in fungal clearance was attributable to AZM’s impact on macrophages rather than any direct antifungal activity against <em>Aspergillus fumigatus.</em></div></div><div><h3>Conclusion</h3><div>These findings suggest AZM enhances macrophage function, boosting anti-inflammatory responses and improving fungal clearance.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107087"},"PeriodicalIF":2.8,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suvi T Jokiranta , Anh Nguyen Ngoc , Xiaobo Huang , Kirsten Nowlan , Leo Hannolainen , Lari Pyöriä , Pirkka T Pekkarinen , Pia Dürnsteiner , Tinja Lääveri , Nelli Heikkilä , Santtu Heinonen , Sini M Laakso , Anu Kantele , Olli Vapalahti , Tomas Strandin , Jussi Hepojoki , Maria F Perdomo , Eliisa Kekäläinen
{"title":"B cell dysregulation during acute COVID-19 is transient","authors":"Suvi T Jokiranta , Anh Nguyen Ngoc , Xiaobo Huang , Kirsten Nowlan , Leo Hannolainen , Lari Pyöriä , Pirkka T Pekkarinen , Pia Dürnsteiner , Tinja Lääveri , Nelli Heikkilä , Santtu Heinonen , Sini M Laakso , Anu Kantele , Olli Vapalahti , Tomas Strandin , Jussi Hepojoki , Maria F Perdomo , Eliisa Kekäläinen","doi":"10.1016/j.imlet.2025.107086","DOIUrl":"10.1016/j.imlet.2025.107086","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19 is still a significant health concern worldwide. B cell responses to COVID-19 have been extensively studied in acute severe disease, but less so during extended follow-up or mild disease. Persisting immunological changes together with herpesvirus reactivations during acute COVID-19 have been suggested as contributing factors for post-acute sequelae of COVID-19 (PASC). Here, we evaluated the natural kinetics of B cell subpopulations together with serological markers of increased B cell activity during acute COVID-19 and long-term follow-up. We also measured human herpesvirus reactivations during acute COVID-19.</div></div><div><h3>Methods</h3><div>We collected plasma and peripheral blood mononuclear cell samples from 120 SARS-CoV-2 positive patients (outpatients = 56, inpatients = 64) at up to five timepoints during acute disease and recovery (up to 460 days since symptom onset, dsso). We determined circulating B cell and Th cell subpopulations using flow cytometry, and measured free light chains, in addition to Epstein-Barr virus (EBV) serology, and herpesvirus qPCR from the plasma samples. The presence of anosmia as a proxy for PASC was self-reported at 3–12 months post-COVID.</div></div><div><h3>Results</h3><div>All changes in B cell subpopulation proportions normalized within 200 dsso. Likewise, the acute alterations observed in circulating T follicular helper and T follicular regulatory cell proportions stabilized soon after. Free light chains were high in acute COVID-19, especially in inpatients, but normalized during follow-up. EBV and human herpesvirus 6B (HHV-6B) reactivations were significantly more common in inpatients than outpatients, with reactivation in 47 and 19 % of inpatients and 4.3 and 0 % of outpatients respectively. Anosmia was not significantly associated with any herpesvirus reactivation.</div></div><div><h3>Conclusions</h3><div>The circulating B cell and Th cell subpopulations experience transitional changes during SARS-CoV-2 infection, but these changes recover in follow-up. EBV and HHV-6B reactivations are common in inpatients, but they are not associated with persisting anosmia.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107086"},"PeriodicalIF":2.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amir Ali Hamidieh , Maryam Behfar , Negar Nejati , Sadaf Setare Azar , Mohammad Taha Salmanifard Ardestani , Romana Malik , Homa Kashani , Rashin Mohseni , Leila Jafari
{"title":"Importance of BCG Vaccination at birth in Pediatric Patients with Chronic Granulomatous Disease after Hematopoietic Stem Cell Transplantation in Developing Countries","authors":"Amir Ali Hamidieh , Maryam Behfar , Negar Nejati , Sadaf Setare Azar , Mohammad Taha Salmanifard Ardestani , Romana Malik , Homa Kashani , Rashin Mohseni , Leila Jafari","doi":"10.1016/j.imlet.2025.107083","DOIUrl":"10.1016/j.imlet.2025.107083","url":null,"abstract":"<div><h3>Introduction</h3><div>Recent advances in hematopoietic stem cell transplantation (HSCT) have improved clinical outcomes; however, various factors continue to influence HSCT success, especially vaccination in immunocompromised patients who receive vaccination at birth. While several studies have investigated the efficacy of vaccines in Chronic Granulomatous Disease (CGD) patients, the specific impact of vaccination on HSCT outcomes in these patients has not yet been studied. This study aimed to address an important gap in the current literature by investigating the effects of BCG vaccination on HSCT outcomes in patients with CGD.</div></div><div><h3>Participants and Methods</h3><div>In this prospective study, 24 pediatric patients with CGD were enrolled from 2016 to 2022, all of whom received the same reduced-intensity conditioning (RIC) regimen before HSCT. Of these, 12 patients received the Bacillus Calmette-Guérin (BCG) vaccine, while 14 patients were not vaccinated.</div></div><div><h3>Results</h3><div>Contrary to other studies, our results showed that CGD patients who received the BCG vaccine before HSCT experienced varying degrees of BCGosis and BCGitis. Specifically, 8 patients showed symptoms of BCGosis, while 4 patients showed symptoms of BCGitis. In addition, our findings revealed no significant differences in graft-versus-host disease (GvHD) and other complications of HSCT between BCG-vaccinated and non-BCG-vaccinated CGD patients, although the overall survival (OS) rate was lower in the vaccinated group. This may be attributed to the reduced-intensity conditioning regimen applied to all patients which can balance HSCT outcome in CGD patients.</div></div><div><h3>Discussion and conclusion</h3><div>Our study emphasizes the importance of screening and diagnosing immunodeficient patients at birth, especially in developing countries where BCG vaccine is administered at birth, as post- vaccination complications can significantly affect HSCT outcomes and subsequent treatments. BCG vaccination can significantly affect HSCT outcomes and subsequent treatments.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107083"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut microbiota analysis revealed unique biomarkers in Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis","authors":"Sijie Chang , Mingrong Chen , Peiguang Niu , Jinhua Zhang","doi":"10.1016/j.imlet.2025.107082","DOIUrl":"10.1016/j.imlet.2025.107082","url":null,"abstract":"<div><h3>Objectives</h3><div>In this paper, the different characteristics of gut microbiota between Ankylosing Spondylitis (AS), Healthy Control (HC), and Non-radiographic Axial Spondyloarthritis (nr-axSpA) were studied. The AS-nr-axSpA differentiation model was constructed to identify patients with these two phenotypes and help doctors make accurate diagnosis.</div></div><div><h3>Methods</h3><div>Stool samples and blood samples of AS, nr-axSpA, and HC were collected from our hospital. Bacterial lipopolysaccharides and lipopolysaccharides-binding proteins in blood were detected by enzyme-linked immunosorbent assay (ELISA). The V3-V4 region of bacterial 16SrRNA was analyzed by MiSeq PE300 sequencing platform with high throughput. Software such as QIIME, R, Excel, etc. were used for statistical analysis of the data. Random Forest (RF) and Area Under Curve (AUC) methods were used to construct the AS-nr-axSpA differentiation model and identify relevant important markers. Set markers and use the receiver operating characteristic curve (ROC) to judge the accuracy of the model.</div></div><div><h3>Results</h3><div>We studied a total of 59 fecal and corresponding blood samples from 31 AS, 21 nr-axSpA, and 7 HC. There was a significant difference in intestinal α diversity between AS and nr-axSpA patients (Shannon index, <em>P</em> = 0.017). Compared to the nr-axSpA patient population, Streptococcus (<em>P</em> = 0.045), Actinomyces (<em>P</em> = 0.0028), Rothia (<em>P</em> = 0.042), and Oribacterium in the intestinal tract of AS patients <em>P</em> = 0.044) increased significantly. However, Dorea (<em>P</em> = 0.034) and Odoribacter (<em>P</em> = 0.043) were significantly reduced. The AS-nr-axSpA model was constructed using 18 factors including Actinomyces and Odoribacter. ROC analysis was performed on the model and an ROC curve was drawn, with an AUC of 0.78, which is moderate accurate.</div></div><div><h3>Conclusions</h3><div>The gut microbiota of patients with AS differs from that of patients with nr-axSpA. The disturbance of gut microbiota may be one of the conditions for the progression of nr-axSpA to AS. The characteristics of gut microbiota and related bacterial products may serve as characteristic factors for differentiating the phenotypes of these two diseases. The AS-nr-axSpA model may help doctors distinguish patients with different phenotypes, but more robust prospective and standardized studies are needed to confirm these findings.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107082"},"PeriodicalIF":2.8,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}