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 identify 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+ T cells from Japanese patients with SPIDDM were activated by overlapping GAD and IA-2 peptides.
{"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":"10.1016/j.imlet.2025.107084","url":null,"abstract":"<div><div>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.</div><div>We aimed to identify the characteristics of pancreatic islet antigen autoreactive T cells in Japanese patients with SPIDDM.</div><div>Peripheral blood mononuclear cells were obtained from Japanese patients with type 1 diabetes mellitus (T1DM) enrolled in our diabetic cohort study. An <em>ex vivo</em> 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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 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}
Pub Date : 2025-09-08DOI: 10.1016/j.imlet.2025.107088
Ellen Kong , Alex Cucco , Adnan Custovic , Sara Fontanella
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.
{"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}
Pub Date : 2025-09-07DOI: 10.1016/j.imlet.2025.107087
Ivy Antwi, Jarrod R. Fortwendel, Theodore J. Cory
Background
Patients with chronic lung diseases often suffer from pulmonary aspergillosis, caused by Aspergillus fumigatus (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.
Objective
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 Aspergillus fumigatus.
Method
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.
Results
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 Aspergillus fumigatus.
Conclusion
These findings suggest AZM enhances macrophage function, boosting anti-inflammatory responses and improving fungal clearance.
{"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}
Pub Date : 2025-09-05DOI: 10.1016/j.imlet.2025.107086
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
Background
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.
Methods
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.
Results
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.
Conclusions
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.
{"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}
Pub Date : 2025-09-01DOI: 10.1016/j.imlet.2025.107083
Amir Ali Hamidieh , Maryam Behfar , Negar Nejati , Sadaf Setare Azar , Mohammad Taha Salmanifard Ardestani , Romana Malik , Homa Kashani , Rashin Mohseni , Leila Jafari
Introduction
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.
Participants and Methods
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.
Results
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.
Discussion and conclusion
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.
{"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}
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.
Methods
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.
Results
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, P = 0.017). Compared to the nr-axSpA patient population, Streptococcus (P = 0.045), Actinomyces (P = 0.0028), Rothia (P = 0.042), and Oribacterium in the intestinal tract of AS patients P = 0.044) increased significantly. However, Dorea (P = 0.034) and Odoribacter (P = 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.
Conclusions
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.
目的：研究强直性脊柱炎（AS）、健康对照组（HC）和非影像学中轴性脊柱炎（nr-axSpA）患者肠道菌群的不同特征。构建AS-nr-axSpA分化模型，识别这两种表型的患者，帮助医生准确诊断。方法：采集我院AS、nr-axSpA、HC的粪便标本和血液标本。采用酶联免疫吸附试验（ELISA）检测血液中细菌脂多糖和脂多糖结合蛋白的含量。采用MiSeq PE300高通量测序平台对细菌16SrRNA的V3-V4区进行分析。采用QIIME、R、Excel等软件对数据进行统计分析。采用随机森林（Random Forest， RF）和曲线下面积（Area Under Curve， AUC）方法构建AS-nr-axSpA分化模型，识别相关重要标记。设置标记并使用受试者工作特征曲线（ROC）来判断模型的准确性。结果：我们共研究了31例AS、21例nr-axSpA和7例HC的59份粪便和相应的血液样本。AS与nr-axSpA患者肠道α多样性差异有统计学意义（Shannon指数，P=0.017）。与nr-axSpA患者相比，AS患者肠道链球菌（P=0.045）、放线菌（P=0.0028）、罗氏菌（P=0.042）和Oribacterium的数量显著增加（P= 0.044）。Dorea （P=0.034）和Odoribacter （P=0.043）明显减少。采用放线菌、恶臭菌等18个因子构建AS-nr-axSpA模型。对模型进行ROC分析，绘制ROC曲线，AUC为0.78，准确度中等。结论：AS患者的肠道菌群与nr-axSpA患者不同。肠道菌群紊乱可能是nr-axSpA向AS发展的条件之一。肠道菌群和相关细菌产物的特征可能是区分这两种疾病表型的特征因素。AS-nr-axSpA模型可以帮助医生区分不同表型的患者，但需要更强大的前瞻性和标准化的研究来证实这些发现。
{"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}
Pub Date : 2025-08-20DOI: 10.1016/j.imlet.2025.107071
Francisca A. Castillo , Bianca C. Kern , Eduardo J. Villablanca
Inflammatory bowel diseases (IBD) have traditionally been considered T cell-driven disorders; however, accumulating evidence challenges this view and underscores a critical, multifaceted role for B cells in the pathogenesis of chronic intestinal inflammation. In the healthy gut, B cells contribute to immune tolerance and mucosal protection primarily through the production of secretory IgA and the regulation of the microbiota. During IBD, the B cell compartment is markedly altered, characterized by increased infiltration of IgA and IgG-secreting PCs, altered humoral responses against gut microbiota and self-antigens, the formation of tertiary lymphoid structures and the emergence of pro-inflammatory subsets such as interferon-induced Sca1⁺PD-L1⁺ B cells. Experimental models have demonstrated both pathogenic and regulatory roles for B cells, which may explain the limited efficacy of pan-B cell depleting therapies, such as rituximab, in clinical settings. This review highlights the evolving landscape of B cell biology in IBD, emphasizing the need for selective therapeutic approaches that distinguish between protective and pathogenic B cells. A deeper understanding of the spatial, phenotypic, and temporal dynamics of intestinal B cell subsets may facilitate the development of precise immunotherapies in IBD.
{"title":"B cells in inflammatory bowel disease","authors":"Francisca A. Castillo , Bianca C. Kern , Eduardo J. Villablanca","doi":"10.1016/j.imlet.2025.107071","DOIUrl":"10.1016/j.imlet.2025.107071","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) have traditionally been considered T cell-driven disorders; however, accumulating evidence challenges this view and underscores a critical, multifaceted role for B cells in the pathogenesis of chronic intestinal inflammation. In the healthy gut, B cells contribute to immune tolerance and mucosal protection primarily through the production of secretory IgA and the regulation of the microbiota. During IBD, the B cell compartment is markedly altered, characterized by increased infiltration of IgA and IgG-secreting PCs, altered humoral responses against gut microbiota and self-antigens, the formation of tertiary lymphoid structures and the emergence of pro-inflammatory subsets such as interferon-induced Sca1⁺PD-L1⁺ B cells. Experimental models have demonstrated both pathogenic and regulatory roles for B cells, which may explain the limited efficacy of pan-B cell depleting therapies, such as rituximab, in clinical settings. This review highlights the evolving landscape of B cell biology in IBD, emphasizing the need for selective therapeutic approaches that distinguish between protective and pathogenic B cells. A deeper understanding of the spatial, phenotypic, and temporal dynamics of intestinal B cell subsets may facilitate the development of precise immunotherapies in IBD.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107071"},"PeriodicalIF":2.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912456","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}
Pub Date : 2025-08-20DOI: 10.1016/j.imlet.2025.107072
R. Gaderparnah , F. van Beuningen , Y. Lin , S.H. Sadrian , H.M. Reijneveld , H. Krabbe , P. Jonkheijm , H.R. Bouma , R.T. Mankowski
Sepsis remains a major cause of mortality worldwide, driven by a dysregulated host response to infection that leads to life-threatening organ dysfunction. Despite advances in evidence-based medicine, early diagnosis and risk stratification remain significant challenges due to the complex, multifaceted nature of sepsis and substantial interindividual variability in clinical presentation. Current approaches relying on single biomarkers cannot provide comprehensive insights into disease progression, limiting their clinical utility in guiding timely and effective interventions. Given the limitations of current single biomarkers in capturing the complexity of sepsis, there is an urgent need for improved diagnostic approaches. While the discovery of novel biomarkers remains important, combining existing biomarkers may offer a pragmatic and effective strategy to improve diagnostic accuracy by leveraging the strengths of each to compensate for the limitations of other. In this clinical perspective, we highlight the potential of such combined biomarker strategies to enhance diagnostic accuracy, support identification of the infection source, and improve prognostic assessment across the clinical course and into long-term outcomes. We provide examples of key biomarkers and their synergistic potential, emphasizing the need for advanced analytical methods such as machine learning and multi-omics integration to enhance predictive accuracy. Shifting toward multi-component biomarker panels represents a critical step toward a more precise, personalized approach to sepsis management to reduce sepsis-related morbidity and mortality. We advocate for further research and validation efforts to facilitate the clinical implementation of combined biomarker models, ultimately transforming sepsis care.
{"title":"Sepsis as a complex syndrome: Are combined biomarkers the future of diagnosis and prognosis? Clinical perspective","authors":"R. Gaderparnah , F. van Beuningen , Y. Lin , S.H. Sadrian , H.M. Reijneveld , H. Krabbe , P. Jonkheijm , H.R. Bouma , R.T. Mankowski","doi":"10.1016/j.imlet.2025.107072","DOIUrl":"10.1016/j.imlet.2025.107072","url":null,"abstract":"<div><div>Sepsis remains a major cause of mortality worldwide, driven by a dysregulated host response to infection that leads to life-threatening organ dysfunction. Despite advances in evidence-based medicine, early diagnosis and risk stratification remain significant challenges due to the complex, multifaceted nature of sepsis and substantial interindividual variability in clinical presentation. Current approaches relying on single biomarkers cannot provide comprehensive insights into disease progression, limiting their clinical utility in guiding timely and effective interventions. Given the limitations of current single biomarkers in capturing the complexity of sepsis, there is an urgent need for improved diagnostic approaches. While the discovery of novel biomarkers remains important, combining existing biomarkers may offer a pragmatic and effective strategy to improve diagnostic accuracy by leveraging the strengths of each to compensate for the limitations of other. In this clinical perspective, we highlight the potential of such combined biomarker strategies to enhance diagnostic accuracy, support identification of the infection source, and improve prognostic assessment across the clinical course and into long-term outcomes. We provide examples of key biomarkers and their synergistic potential, emphasizing the need for advanced analytical methods such as machine learning and multi-omics integration to enhance predictive accuracy. Shifting toward multi-component biomarker panels represents a critical step toward a more precise, personalized approach to sepsis management to reduce sepsis-related morbidity and mortality. We advocate for further research and validation efforts to facilitate the clinical implementation of combined biomarker models, ultimately transforming sepsis care.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107072"},"PeriodicalIF":2.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890650","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}
Pub Date : 2025-08-12DOI: 10.1016/j.imlet.2025.107067
Helena Gåsland , Nicole H Trier , Cecilie Kyllesbech , Anette H Draborg , Rimantas Slibinskas , Evaldas Ciplys , Danguolė Žiogienė , Alma Gedvilaitė , Rasa Petraitytė-Burneikienė , Jette L Frederiksen , Gunnar Houen
{"title":"Corrigendum to “Antibodies to expanded virus antigen panels show elevated diagnostic sensitivities in multiple sclerosis and optic neuritis” [Immunol. Lett. 254 (2023) 54–64]","authors":"Helena Gåsland , Nicole H Trier , Cecilie Kyllesbech , Anette H Draborg , Rimantas Slibinskas , Evaldas Ciplys , Danguolė Žiogienė , Alma Gedvilaitė , Rasa Petraitytė-Burneikienė , Jette L Frederiksen , Gunnar Houen","doi":"10.1016/j.imlet.2025.107067","DOIUrl":"10.1016/j.imlet.2025.107067","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107067"},"PeriodicalIF":2.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845782","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}
Pub Date : 2025-08-11DOI: 10.1016/j.imlet.2025.107070
Rabia Sare Yanikoglu , Rumeysa Hekimoglu , Mert Celikten , Ayca Yıldız Pekoz , Ali Osman Gurol , Mukaddes Esrefoglu , Nuriye Akev , Tuğba Yılmaz Ozden , Beyza Goncu
Aloe vera, known for its rich phytochemical content, has long been used in traditional medicine. This study aimed to enhance its anti-inflammatory and anti-allergic properties by formulating an intranasal Aloe vera gel with propylene glycol (PgAv) and assessing its efficacy through in vitro and in vivo models. In vitro, PgAv and Aloe vera gel (Av) were tested on LPS-induced HSAEC cells for mRNA expressions of TNFα, IL6, IL1β, and IL5. Co-culture experiments revealed PgAv reduced TNFα and increased IFNγ, promoting a TH1-type response. In vivo, PgAv was administered intranasally to BALB/c mice with OVA-induced allergic airway inflammation model (AIAR). PgAv reduced mRNA expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BAL), decreased TNFα and OVA-IgE levels in plasma, and attenuated eosinophil infiltration and lung inflammation. While PgAv increased IL6 levels, it concurrently reduced PGD2 levels, indicating a therapeutic effect via prostanoid synthesis pathways. PgAv demonstrated superior efficacy compared to Av in modulating inflammatory responses, enhancing TH1 responses for immunological balance, and mitigating TH2-mediated inflammation. These findings suggest PgAv as a promising treatment for allergic airway inflammation, warranting further investigation to clarify the underlying mechanisms.
{"title":"Anti-inflammatory potential of pre-formulated Aloe vera in mitigating allergen-induced airway responses in mice","authors":"Rabia Sare Yanikoglu , Rumeysa Hekimoglu , Mert Celikten , Ayca Yıldız Pekoz , Ali Osman Gurol , Mukaddes Esrefoglu , Nuriye Akev , Tuğba Yılmaz Ozden , Beyza Goncu","doi":"10.1016/j.imlet.2025.107070","DOIUrl":"10.1016/j.imlet.2025.107070","url":null,"abstract":"<div><div>Aloe vera, known for its rich phytochemical content, has long been used in traditional medicine. This study aimed to enhance its anti-inflammatory and anti-allergic properties by formulating an intranasal Aloe vera gel with propylene glycol (PgAv) and assessing its efficacy through <em>in vitro</em> and <em>in vivo</em> models. <em>In vitro</em>, PgAv and Aloe vera gel (Av) were tested on LPS-induced HSAEC cells for mRNA expressions of <em>TNFα, IL6, IL1β</em>, and <em>IL5</em>. Co-culture experiments revealed PgAv reduced TNFα and increased IFNγ, promoting a T<sub>H</sub>1-type response. <em>In vivo</em>, PgAv was administered intranasally to BALB/c mice with OVA-induced allergic airway inflammation model (AIAR). PgAv reduced mRNA expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BAL), decreased TNFα and OVA-IgE levels in plasma, and attenuated eosinophil infiltration and lung inflammation. While PgAv increased IL6 levels, it concurrently reduced PGD2 levels, indicating a therapeutic effect via prostanoid synthesis pathways. PgAv demonstrated superior efficacy compared to Av in modulating inflammatory responses, enhancing T<sub>H</sub>1 responses for immunological balance, and mitigating T<sub>H</sub>2-mediated inflammation. These findings suggest PgAv as a promising treatment for allergic airway inflammation, warranting further investigation to clarify the underlying mechanisms.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107070"},"PeriodicalIF":2.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840936","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}
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