Pub Date : 2025-10-18DOI: 10.1016/j.clim.2025.110612
Jesús Daniel Zambrano-Romero , Diana Berenice Ríos-Ramírez, Verónica Yutsil García-Rasilla, Blanca Estela Ruiz-Medina, Paula Licona-Limón
Transforming growth factor β (TGF-β) is recognized as an anti-inflammatory cytokine that negatively affects effector CD8 T cells. However, its impact is not confined to the effector CD8 T cell population; TGF-β also plays a role in suppressing naïve CD8 T cell activation, preserving stemness, and influencing the function and differentiation of memory CD8 T cells. Memory CD8 T cells are vital for eradicating pathogens that have previously infected the host. Both tissue-resident and central memory CD8 T cells have demonstrated a dependency on TGF-β for their differentiation. The mechanisms underlying many of these TGF-β effects remain unclear. This review summarizes the roles of TGF-β in various CD8 T cell subsets, with an emphasis on the memory T cell compartment, and discusses recent findings regarding its influence on memory CD8 T cell differentiation as well as open questions in the field.
{"title":"TGF-β: A silent player regulating CD8 T cell memory","authors":"Jesús Daniel Zambrano-Romero , Diana Berenice Ríos-Ramírez, Verónica Yutsil García-Rasilla, Blanca Estela Ruiz-Medina, Paula Licona-Limón","doi":"10.1016/j.clim.2025.110612","DOIUrl":"10.1016/j.clim.2025.110612","url":null,"abstract":"<div><div>Transforming growth factor β (TGF-β) is recognized as an anti-inflammatory cytokine that negatively affects effector CD8 T cells. However, its impact is not confined to the effector CD8 T cell population; TGF-β also plays a role in suppressing naïve CD8 T cell activation, preserving stemness, and influencing the function and differentiation of memory CD8 T cells. Memory CD8 T cells are vital for eradicating pathogens that have previously infected the host. Both tissue-resident and central memory CD8 T cells have demonstrated a dependency on TGF-β for their differentiation. The mechanisms underlying many of these TGF-β effects remain unclear. This review summarizes the roles of TGF-β in various CD8 T cell subsets, with an emphasis on the memory T cell compartment, and discusses recent findings regarding its influence on memory CD8 T cell differentiation as well as open questions in the field.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110612"},"PeriodicalIF":3.8,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336785","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}
Pub Date : 2025-10-16DOI: 10.1016/j.clim.2025.110613
Islam M. Ghazi , Ahmed F. Omar , Wasim S. El Nekidy , Gehan Harb , Diaa Alrahmany
Introduction
Inherited hematological disorders, affecting immune cell quantity and function, compromise immune system efficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited enzymopathy and has been implicated in compromised immune cell function and host defense, and in elevating infection vulnerability. This study explores the impact of G6PD deficiency on immune cellular response and infection-related mortality.
Method
Adults with G6PD deficiency and bacterial infections (2017–2021) were analyzed. Demographics, comorbidities, laboratory parameters, and microbiological data were assessed. Cox proportional hazards regression analyzed the association between white blood cell (WBC) count and 28-day mortality. The data analysis was conducted using the R software statistical programming language.
Results
The investigation included 334 bacterial infection episodes representing 202 unique patients who fulfilled the inclusion criteria. A 19.2 % 28-day mortality rate was observed. Males, those aged ≥60, and patients with comorbidities had higher mortality. Anemia, high globulin, and elevated liver enzymes were associated with mortality. The majority of patients demonstrated reduced WBC counts (<9.8 × 109/L) during infection, significantly contributing to increased mortality risk (HR: 1.95, p = 0.008). Males exhibited a more pronounced impact. This study reveals heightened mortality risk in G6PD-deficient patients with diminished WBC counts during infections. Elevated CRP, globulins, and liver enzymes indicated severe infections, contrasting the unexpected non-response in WBC counts.
Conclusion
Vigilance in treating infections in G6PD-deficient patients, especially in males, is crucial for favorable outcomes. Diagnostic reliance on altered WBC counts in this population may misguide clinical decisions. G6PD deficiency poses a unique challenge in infection management, emphasizing the need for tailored interventions and exploration of alternative biomarkers for assessing severity and predicting mortality. Further studies and larger cohorts are essential for a comprehensive understanding and improved clinical practices.
简介：遗传性血液病，影响免疫细胞的数量和功能，损害免疫系统的效率。葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是最常见的x连锁遗传性酶病，与免疫细胞功能和宿主防御受损以及感染易感性升高有关。本研究探讨G6PD缺乏对免疫细胞反应和感染相关死亡率的影响。方法：分析2017-2021年G6PD缺乏症和细菌感染的成年人。评估了人口统计学、合并症、实验室参数和微生物学数据。Cox比例风险回归分析白细胞（WBC）计数与28天死亡率之间的关系。数据分析采用R软件统计编程语言进行。结果：调查包括334例细菌感染事件，代表202例符合纳入标准的独特患者。28天死亡率为19.2 %。年龄≥60岁的男性和有合并症的患者死亡率较高。贫血、高球蛋白和肝酶升高与死亡率相关。大多数患者在感染期间表现出白细胞计数减少（9/L），这显著增加了死亡风险（HR: 1.95, p = 0.008）。男性表现出更明显的影响。该研究揭示了感染期间WBC计数减少的g6pd缺陷患者的死亡风险增加。升高的CRP，球蛋白和肝酶表明严重感染，与WBC计数的意外无反应形成对比。结论：警惕治疗g6pd缺陷患者，尤其是男性患者的感染，是获得良好结果的关键。在这一人群中，对白细胞计数改变的诊断依赖可能会误导临床决策。G6PD缺乏症对感染管理提出了独特的挑战，强调需要量身定制的干预措施和探索替代生物标志物来评估严重程度和预测死亡率。进一步的研究和更大的队列对于全面理解和改进临床实践是必不可少的。
{"title":"Innate immune response to bacterial infections in hospitalized glucose-6-phosphate dehydrogenase-deficient patients; diagnostic value of white blood cell count","authors":"Islam M. Ghazi , Ahmed F. Omar , Wasim S. El Nekidy , Gehan Harb , Diaa Alrahmany","doi":"10.1016/j.clim.2025.110613","DOIUrl":"10.1016/j.clim.2025.110613","url":null,"abstract":"<div><h3>Introduction</h3><div>Inherited hematological disorders, affecting immune cell quantity and function, compromise immune system efficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited enzymopathy and has been implicated in compromised immune cell function and host defense, and in elevating infection vulnerability. This study explores the impact of G6PD deficiency on immune cellular response and infection-related mortality.</div></div><div><h3>Method</h3><div>Adults with G6PD deficiency and bacterial infections (2017–2021) were analyzed. Demographics, comorbidities, laboratory parameters, and microbiological data were assessed. Cox proportional hazards regression analyzed the association between white blood cell (WBC) count and 28-day mortality. The data analysis was conducted using the R software statistical programming language.</div></div><div><h3>Results</h3><div>The investigation included 334 bacterial infection episodes representing 202 unique patients who fulfilled the inclusion criteria. A 19.2 % 28-day mortality rate was observed. Males, those aged ≥60, and patients with comorbidities had higher mortality. Anemia, high globulin, and elevated liver enzymes were associated with mortality. The majority of patients demonstrated reduced WBC counts (<9.8 × 10<sup>9</sup>/L) during infection, significantly contributing to increased mortality risk (HR: 1.95, <em>p</em> = 0.008). Males exhibited a more pronounced impact. This study reveals heightened mortality risk in G6PD-deficient patients with diminished WBC counts during infections. Elevated CRP, globulins, and liver enzymes indicated severe infections, contrasting the unexpected non-response in WBC counts.</div></div><div><h3>Conclusion</h3><div>Vigilance in treating infections in G6PD-deficient patients, especially in males, is crucial for favorable outcomes. Diagnostic reliance on altered WBC counts in this population may misguide clinical decisions. G6PD deficiency poses a unique challenge in infection management, emphasizing the need for tailored interventions and exploration of alternative biomarkers for assessing severity and predicting mortality. Further studies and larger cohorts are essential for a comprehensive understanding and improved clinical practices.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110613"},"PeriodicalIF":3.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318096","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}
Pub Date : 2025-10-13DOI: 10.1016/j.clim.2025.110609
Emmanuel Ledoult , Thomas Guerrier , Sylvain Dubucquoi , Martin Figeac , Céline Villenet , Blanche Daunou , Helene Behal , Mohammad Ryadh Pokeerbux , Thomas Machet , Vincent Koether , Aurore Collet , David Launay , Lille Covid Research network (LICORNE)
COVID-19 induces a marked plasmablast (PB) expansion, whose functional role remains unclear. We performed B-cell immunophenotyping and multiplex cytokine analysis in a prospective cohort of 50 COVID-19 patients. PB expansion occurred early and correlated with both maximal disease severity and inflammatory markers. A retrospective cohort of 282 steroid-naïve patients was used to validate PB dynamics, model trajectories, and perform transcriptomic profiling. Two PB trajectories emerged: a transient one and a persistent, amplified one, the latter associated with a sixfold increase in 30-day mortality (p < 0.001). In severe cases, PB upregulated purine metabolism genes; in non-severe cases, they expressed interferon and CIITA-mediated MHC-II programs. BAFF levels at day 7 correlated with severity suggesting a role in sustaining PB expansion. PB exhibit functional duality in COVID-19—acting as immune regulators in non-severe cases and as inflammation amplifiers in severe disease. BAFF emerges as a potential therapeutic target in PB-driven immune dysregulation.
Trial registration.ClinicalTrials.govNCT04327180 and NCT04341792.
{"title":"Dual role of plasmablasts as immune regulators or amplifiers in COVID-19","authors":"Emmanuel Ledoult , Thomas Guerrier , Sylvain Dubucquoi , Martin Figeac , Céline Villenet , Blanche Daunou , Helene Behal , Mohammad Ryadh Pokeerbux , Thomas Machet , Vincent Koether , Aurore Collet , David Launay , Lille Covid Research network (LICORNE)","doi":"10.1016/j.clim.2025.110609","DOIUrl":"10.1016/j.clim.2025.110609","url":null,"abstract":"<div><div>COVID-19 induces a marked plasmablast (PB) expansion, whose functional role remains unclear. We performed B-cell immunophenotyping and multiplex cytokine analysis in a prospective cohort of 50 COVID-19 patients. PB expansion occurred early and correlated with both maximal disease severity and inflammatory markers. A retrospective cohort of 282 steroid-naïve patients was used to validate PB dynamics, model trajectories, and perform transcriptomic profiling. Two PB trajectories emerged: a transient one and a persistent, amplified one, the latter associated with a sixfold increase in 30-day mortality (<em>p</em> < 0.001). In severe cases, PB upregulated purine metabolism genes; in non-severe cases, they expressed interferon and CIITA-mediated MHC-II programs. BAFF levels at day 7 correlated with severity suggesting a role in sustaining PB expansion. PB exhibit functional duality in COVID-19—acting as immune regulators in non-severe cases and as inflammation amplifiers in severe disease. BAFF emerges as a potential therapeutic target in PB-driven immune dysregulation.</div><div><strong>Trial registration.</strong> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> <span><span>NCT04327180</span><svg><path></path></svg></span> and <span><span>NCT04341792</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110609"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298833","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}
Pub Date : 2025-10-11DOI: 10.1016/j.clim.2025.110608
Victoria Hyslop Hvalkof, Malene Bredahl Hansen, Sahla El Mahdaoui, Marie Mathilde Hansen, Jeppe Romme Christensen, Sophie Buhelt, Finn Sellebjerg, Helle Bach Søndergaard
Epstein-Barr virus (EBV) may be crucial for development of multiple sclerosis (MS). EBV encodes 44 microRNAs (miRNAs) that are found in exosomes. We investigated EBV miRNAs in cerebrospinal fluid (CSF) exosomes in 50 newly diagnosed people with relapsing-remitting MS (pwRRMS), 24 with clinically isolated syndromes (CIS), 45 symptomatic controls (SC), 15 anti-CD20 antibody-treated 24 natalizumab (NTZ)-treated pwRRMS. miRNAs were measured by quantitative PCR. Plasma anti-EBNA1 antibody and various CSF biomarkers were measured by immunoassays. ebv-miR-BART13-5p and ebv-miR-BART19-3p were reliably measured. ebv-miR-BART19-3p was lower in pwRRMS and correlated with disease severity. In NTZ-treated pwRRMS, ebv-miR-BART19-3p was higher, correlated with treatment duration, and was associated with soluble B-cell maturation antigen, CD27, and zonula occludens-1. No differences were observed in anti-CD20 antibody-treated pwRRMS. These findings may reflect the presence of more exosome recipient cells in pwRRMS, resulting in fewer exosomes as they become internalized in recipient cells along with their EBV miRNA cargo.
{"title":"Cerebrospinal fluid exosomal Epstein-Barr virus microRNAs in multiple sclerosis and effects of disease modifying therapies","authors":"Victoria Hyslop Hvalkof, Malene Bredahl Hansen, Sahla El Mahdaoui, Marie Mathilde Hansen, Jeppe Romme Christensen, Sophie Buhelt, Finn Sellebjerg, Helle Bach Søndergaard","doi":"10.1016/j.clim.2025.110608","DOIUrl":"10.1016/j.clim.2025.110608","url":null,"abstract":"<div><div>Epstein-Barr virus (EBV) may be crucial for development of multiple sclerosis (MS). EBV encodes 44 microRNAs (miRNAs) that are found in exosomes. We investigated EBV miRNAs in cerebrospinal fluid (CSF) exosomes in 50 newly diagnosed people with relapsing-remitting MS (pwRRMS), 24 with clinically isolated syndromes (CIS), 45 symptomatic controls (SC), 15 anti-CD20 antibody-treated 24 natalizumab (NTZ)-treated pwRRMS. miRNAs were measured by quantitative PCR. Plasma anti-EBNA1 antibody and various CSF biomarkers were measured by immunoassays. ebv-miR-BART13-5p and ebv-miR-BART19-3p were reliably measured. ebv-miR-BART19-3p was lower in pwRRMS and correlated with disease severity. In NTZ-treated pwRRMS, ebv-miR-BART19-3p was higher, correlated with treatment duration, and was associated with soluble B-cell maturation antigen, CD27, and zonula occludens-1. No differences were observed in anti-CD20 antibody-treated pwRRMS. These findings may reflect the presence of more exosome recipient cells in pwRRMS, resulting in fewer exosomes as they become internalized in recipient cells along with their EBV miRNA cargo.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110608"},"PeriodicalIF":3.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285746","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}
Pub Date : 2025-10-10DOI: 10.1016/j.clim.2025.110604
Yilin Hou , Lin Sun , Mengqi Su , Weiqiang Yang , Lingchao Ji , Yaqi Zhou , Xiaochan Lu , Na Yin , Jiaqi Zhao , Zihan Qiu , Yi Wei , Weiping Wen , HongYi Hu
Background
Neurotrophins are elevated in nasal polyps (NPs) and/or allergies, exerting neurogenic inflammatory effects. Non-classical glial-derived neurotrophic factor (GDNF) family ligands (GFLs) remain poorly understood in chronic rhinosinusitis with NP (CRSwNP).
Methods
GDNF expression was analyzed in 67 nasal fluids (NFs) and 44 tissues via proteomic, transcriptomic, and immunohistochemical assays. Immunofluorescence co-staining identified GDNF and p63 + basal cells (BCs). Functional studies in human nasal epithelial cells (HNECs) assessed GDNF's affects on proliferation and barrier integrity. Bioinformatics identified regulatory networks and drug candidates.
Results
GDNF existed in NFs and tissues of CRSwNP, with higher abundance in eosinophilic NPs. P63 + BCs expression positively correlates with GDNF levels. GDNF potently activated MAPK/PI3K/Akt signaling in HNECs and induced Ki-67+/p63 + cells proliferation, while reduced distribution of claudin-1 at junctions. miR-204-5p/211-5p and two FDA-approved neuroactive drugs were predicted as GDNF modulators.
Conclusions
GDNF drives aberrant epithelial remodeling in CRSwNP via MAPK/PI3K signaling, highlighting its therapeutic potential for refractory disease.
{"title":"Glial-derived neurotrophic factor promotes aberrant basal cell hyperplasia in nasal polyps","authors":"Yilin Hou , Lin Sun , Mengqi Su , Weiqiang Yang , Lingchao Ji , Yaqi Zhou , Xiaochan Lu , Na Yin , Jiaqi Zhao , Zihan Qiu , Yi Wei , Weiping Wen , HongYi Hu","doi":"10.1016/j.clim.2025.110604","DOIUrl":"10.1016/j.clim.2025.110604","url":null,"abstract":"<div><h3>Background</h3><div>Neurotrophins are elevated in nasal polyps (NPs) and/or allergies, exerting neurogenic inflammatory effects. Non-classical glial-derived neurotrophic factor (GDNF) family ligands (GFLs) remain poorly understood in chronic rhinosinusitis with NP (CRSwNP).</div></div><div><h3>Methods</h3><div>GDNF expression was analyzed in 67 nasal fluids (NFs) and 44 tissues via proteomic, transcriptomic, and immunohistochemical assays. Immunofluorescence co-staining identified GDNF and p63 + basal cells (BCs). Functional studies in human nasal epithelial cells (HNECs) assessed GDNF's affects on proliferation and barrier integrity. Bioinformatics identified regulatory networks and drug candidates.</div></div><div><h3>Results</h3><div>GDNF existed in NFs and tissues of CRSwNP, with higher abundance in eosinophilic NPs. P63 + BCs expression positively correlates with GDNF levels. GDNF potently activated MAPK/PI3K/Akt signaling in HNECs and induced Ki-67+/p63 + cells proliferation, while reduced distribution of claudin-1 at junctions. miR-204-5p/211-5p and two FDA-approved neuroactive drugs were predicted as GDNF modulators.</div></div><div><h3>Conclusions</h3><div>GDNF drives aberrant epithelial remodeling in CRSwNP via MAPK/PI3K signaling, highlighting its therapeutic potential for refractory disease.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110604"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274147","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}
Pub Date : 2025-10-10DOI: 10.1016/j.clim.2025.110607
Julia Snyder , Marni Slavik , Patrick Harvey , Roxana Del Rio-Guerra , Bernardo A. Mainou , Alessandro Sette , Beth D. Kirkpatrick , Alba Grifoni , Jessica W. Crothers
Summary
Little is known about the immunologic mechanisms responsible for observed differences in mucosal immunity following vaccination with oral live attenuated polio vaccines (OPVs) compared to inactivated polio vaccines (IPVs). Here, we used a flow cytometric activation-induced marker (AIM)-based approach to investigate vaccine-related differences in T cell response using peripheral blood samples from healthy adults enrolled in two polio vaccine trials. Our findings indicate that vaccination with OPVs (1) enhances CD4+ T cell responses, and (2) expands CD4+ and CD8+ antigen recognition of non-structural proteins. Fecal shedding of OPVs was associated with enhanced T cell responses, and primary CD8+ T cell responses appear to correlate with early control of fecal viral shedding. Our results indicate that OPVs induce broad cellular immunity to polioviruses, which may help explain their enhanced ability to stimulate effective pathogen-specific mucosal immunity.
{"title":"Oral live attenuated polio vaccines induce enhanced T-cell responses with broad antigen recognition compared to inactivated polio vaccines","authors":"Julia Snyder , Marni Slavik , Patrick Harvey , Roxana Del Rio-Guerra , Bernardo A. Mainou , Alessandro Sette , Beth D. Kirkpatrick , Alba Grifoni , Jessica W. Crothers","doi":"10.1016/j.clim.2025.110607","DOIUrl":"10.1016/j.clim.2025.110607","url":null,"abstract":"<div><h3>Summary</h3><div>Little is known about the immunologic mechanisms responsible for observed differences in mucosal immunity following vaccination with oral live attenuated polio vaccines (OPVs) compared to inactivated polio vaccines (IPVs). Here, we used a flow cytometric activation-induced marker (AIM)-based approach to investigate vaccine-related differences in T cell response using peripheral blood samples from healthy adults enrolled in two polio vaccine trials. Our findings indicate that vaccination with OPVs (1) enhances CD4+ T cell responses, and (2) expands CD4+ and CD8+ antigen recognition of non-structural proteins. Fecal shedding of OPVs was associated with enhanced T cell responses, and primary CD8+ T cell responses appear to correlate with early control of fecal viral shedding. Our results indicate that OPVs induce broad cellular immunity to polioviruses, which may help explain their enhanced ability to stimulate effective pathogen-specific mucosal immunity.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110607"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279098","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}
B cells contribute to systemic lupus erythematosus (SLE) pathogenesis through autoantibody production. DNA hypomethylation in B cells is a hallmark of SLE and may be associated with altered expression of key epigenetic regulators. This study investigated the mRNA expression of DNMT1 and UHRF1, which maintain DNA methylation, and TET2 and TET3, which mediate demethylation, in B cells from SLE patients.
Methods
Participants included individuals with active SLE, inactive SLE, and healthy controls. Purified B cells were stimulated in vitro with anti-human IgM. Gene expression of DNMT1, UHRF1, TET2, and TET3 was quantified by qRT-PCR
Results
At baseline, UHRF1 mRNA expression was significantly decreased, and TET3 expression significantly increased in B cells from active SLE patients compared to controls. Upon anti-IgM activation, further reductions in UHRF1 and increases in TET3 expression were observed in active SLE B cells. DNMT1 and TET2 expression did not differ significantly across groups or conditions.
Conclusion
The altered expression of UHRF1 and TET3 mRNA in B cells from active SLE patients may reflect underlying epigenetic dysregulation associated with disease activity. These findings provide preliminary support for further investigation into their potential involvement in the pathobiology of SLE.
{"title":"Altered methylation-related genes expression in B cells of systemic lupus erythematosus patients","authors":"Amin Azizan , Elham Farhadi , Seyedeh Tahereh Faezi , Majid Alikhani , Mahdi Mahmoudi , Ahmadreza Jamshidi , Mohammad Vodjgani","doi":"10.1016/j.clim.2025.110606","DOIUrl":"10.1016/j.clim.2025.110606","url":null,"abstract":"<div><h3>Background and objective</h3><div>B cells contribute to systemic lupus erythematosus (SLE) pathogenesis through autoantibody production. DNA hypomethylation in B cells is a hallmark of SLE and may be associated with altered expression of key epigenetic regulators. This study investigated the mRNA expression of DNMT1 and UHRF1, which maintain DNA methylation, and TET2 and TET3, which mediate demethylation, in B cells from SLE patients.</div></div><div><h3>Methods</h3><div>Participants included individuals with active SLE, inactive SLE, and healthy controls. Purified B cells were stimulated in vitro with anti-human IgM. Gene expression of DNMT1, UHRF1, TET2, and TET3 was quantified by qRT-PCR</div></div><div><h3>Results</h3><div>At baseline, UHRF1 mRNA expression was significantly decreased, and TET3 expression significantly increased in B cells from active SLE patients compared to controls. Upon anti-IgM activation, further reductions in UHRF1 and increases in TET3 expression were observed in active SLE B cells. DNMT1 and TET2 expression did not differ significantly across groups or conditions.</div></div><div><h3>Conclusion</h3><div>The altered expression of UHRF1 and TET3 mRNA in B cells from active SLE patients may reflect underlying epigenetic dysregulation associated with disease activity. These findings provide preliminary support for further investigation into their potential involvement in the pathobiology of SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110606"},"PeriodicalIF":3.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274121","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}
Pub Date : 2025-10-02DOI: 10.1016/j.clim.2025.110605
Jagoda Siemaszko , Piotr Łacina , Donata Szymczak , Agnieszka Szeremet , Maciej Majcherek , Anna Czyż , Małgorzata Sobczyk-Kruszelnicka , Wojciech Fidyk , Iwona Solarska , Barbara Nasiłowska-Adamska , Patrycja Skowrońska , Maria Bieniaszewska , Agnieszka Tomaszewska , Grzegorz W. Basak , Sebastian Giebel , Tomasz Wróbel , Katarzyna Bogunia-Kubik
Background
NK cell activity after allogeneic haematopoietic stem cell transplantation (HSCT) is still not fully understood. Their cytotoxic activity is modulated by a range of inhibitory and activating surface receptors. Among these, the inhibitory receptors ILT-2 and ILT-4 have yet to be explored in relation to HSCT and its outcomes.
Methods
Genotyping for ILT-2 and ILT-4 was performed using TaqMan assays. ILT-2 and ILT-4 surface expression on NK cells was assessed by flow cytometry. Levels of sHLA-F and sHLA-G were determined using ELISA. mRNA expression of ILT-2, ILT-4 and IFN-γ was measured with quantitative real-time PCR with TaqMan Gene Expression probes.
Results
Presence of donor ILT-2 rs1061681 T allele was associated with increased risk of chronic graft-versus-host disease (cGVHD) (p = 0.0239). Donor ILT-4 rs1128646 T allele was related with decreased risk of overall survival after HSCT (p = 0.0506) and with higher risk of acute GvHD (aGvHD) (p = 0.0834). Serum levels of sHLA-F and sHLA-G were significantly higher at day +30 than day +90 after HSCT (p = 0.0002 and p < 0.0001, respectively). Expression of ILT2 at mRNA level was significantly decreased among recipients with aGvHD (p = 0.0266). ILT-4 expression correlated negatively with expression of interferon gamma (p = 0.0280, R = -0.532). The percentages of LILRB1/ILT-2+ and LILRB2/ILT4+ NK cells were the highest at day +21 after HSCT (p = 0.0014 and p < 0.0001 for ILT-2 and ILT-4, respectively).
Conclusions
Both ILT-2 and ILT-4 inhibitory receptors were found to be associated with allogeneic HSCT outcome. This suggests that ILT receptor expression on NK cells may potentially play a role in post-transplant complications.
{"title":"ILT-2 and ILT-4 expression and donor genotype as factors associated with HSCT outcome","authors":"Jagoda Siemaszko , Piotr Łacina , Donata Szymczak , Agnieszka Szeremet , Maciej Majcherek , Anna Czyż , Małgorzata Sobczyk-Kruszelnicka , Wojciech Fidyk , Iwona Solarska , Barbara Nasiłowska-Adamska , Patrycja Skowrońska , Maria Bieniaszewska , Agnieszka Tomaszewska , Grzegorz W. Basak , Sebastian Giebel , Tomasz Wróbel , Katarzyna Bogunia-Kubik","doi":"10.1016/j.clim.2025.110605","DOIUrl":"10.1016/j.clim.2025.110605","url":null,"abstract":"<div><h3>Background</h3><div>NK cell activity after allogeneic haematopoietic stem cell transplantation (HSCT) is still not fully understood. Their cytotoxic activity is modulated by a range of inhibitory and activating surface receptors. Among these, the inhibitory receptors ILT-2 and ILT-4 have yet to be explored in relation to HSCT and its outcomes.</div></div><div><h3>Methods</h3><div>Genotyping for ILT-2 and ILT-4 was performed using TaqMan assays. ILT-2 and ILT-4 surface expression on NK cells was assessed by flow cytometry. Levels of sHLA-F and sHLA-G were determined using ELISA. mRNA expression of <em>ILT-2</em>, <em>ILT-4</em> and <em>IFN-γ</em> was measured with quantitative real-time PCR with TaqMan Gene Expression probes.</div></div><div><h3>Results</h3><div>Presence of donor ILT-2 rs1061681 <em>T</em> allele was associated with increased risk of chronic graft-versus-host disease (cGVHD) (<em>p</em> = 0.0239). Donor ILT-4 rs1128646 <em>T</em> allele was related with decreased risk of overall survival after HSCT (<em>p</em> = 0.0506) and with higher risk of acute GvHD (aGvHD) (<em>p</em> = 0.0834). Serum levels of sHLA-F and sHLA-G were significantly higher at day +30 than day +90 after HSCT (<em>p</em> = 0.0002 and <em>p</em> < 0.0001, respectively). Expression of ILT2 at mRNA level was significantly decreased among recipients with aGvHD (<em>p</em> = 0.0266). ILT-4 expression correlated negatively with expression of interferon gamma (<em>p</em> = 0.0280, R = -0.532). The percentages of <em>LILRB1</em>/ILT-2+ and <em>LILRB2</em>/ILT4+ NK cells were the highest at day +21 after HSCT (<em>p</em> = 0.0014 and <em>p</em> < 0.0001 for ILT-2 and ILT-4, respectively).</div></div><div><h3>Conclusions</h3><div>Both ILT-2 and ILT-4 inhibitory receptors were found to be associated with allogeneic HSCT outcome. This suggests that ILT receptor expression on NK cells may potentially play a role in post-transplant complications.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110605"},"PeriodicalIF":3.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228466","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}
Pub Date : 2025-09-11DOI: 10.1016/j.clim.2025.110603
Hai-Feng Li , Shi-Min Hu , Wei Han , Yan-Su Guo
{"title":"Regarding the “Efgartigimod versus standard of care in new-onset AChR subtype generalized myasthenia gravis: A prospective cohort study”","authors":"Hai-Feng Li , Shi-Min Hu , Wei Han , Yan-Su Guo","doi":"10.1016/j.clim.2025.110603","DOIUrl":"10.1016/j.clim.2025.110603","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110603"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058430","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}
Pub Date : 2025-09-05DOI: 10.1016/j.clim.2025.110596
Youmna El-Orfali , Hagop Mardirossian , Habib Al-Kalamouni , Zeinab El-Zein , Samar Dalle , Dima Khreis , Amani Haddara , Rima Hanna-Wakim , Ghassan Dbaibo , Michel J. Massaad
Chronic Granulomatous Disease (CGD) is caused by mutations in the NADPH oxidase complex that impair the ability of phagocytes to eliminate injested pathogens. As a result, patients with CGD suffer from recurrent infections and chronic inflammation. We report the clinical, biochemical, and genetic basis of the disease in 17 CGD patients from Lebanon. Whole exome sequencing (WES) identified 2 distinct mutations in NCF2 resulting in the deletion of exons 3 and 5, accounting for 82 % of the cases that underwent WES. This high prevalence provided the rationale for a diagnostic strategy involving assessment of NADPH oxidase function, identification of the affected protein, and targeted gene sequencing. Using this approach, 3 additional CGD patients with simmilar deletions were identified, supporting the presence of a founder effect in the Lebanese population. This biochemical and tageted sequencing approach is rapid, reliable, and cost-effective, making it a particularly valuable diagnostic option for families who cannot afford WES.
{"title":"Clinical, biochemical, and genetic characterization of Lebanese patients with chronic granulomatous disease due to NCF2 pathogenic variants","authors":"Youmna El-Orfali , Hagop Mardirossian , Habib Al-Kalamouni , Zeinab El-Zein , Samar Dalle , Dima Khreis , Amani Haddara , Rima Hanna-Wakim , Ghassan Dbaibo , Michel J. Massaad","doi":"10.1016/j.clim.2025.110596","DOIUrl":"10.1016/j.clim.2025.110596","url":null,"abstract":"<div><div>Chronic Granulomatous Disease (CGD) is caused by mutations in the NADPH oxidase complex that impair the ability of phagocytes to eliminate injested pathogens. As a result, patients with CGD suffer from recurrent infections and chronic inflammation. We report the clinical, biochemical, and genetic basis of the disease in 17 CGD patients from Lebanon. Whole exome sequencing (WES) identified 2 distinct mutations in <em>NCF2</em> resulting in the deletion of exons 3 and 5, accounting for 82 % of the cases that underwent WES. This high prevalence provided the rationale for a diagnostic strategy involving assessment of NADPH oxidase function, identification of the affected protein, and targeted gene sequencing. Using this approach, 3 additional CGD patients with simmilar deletions were identified, supporting the presence of a founder effect in the Lebanese population. This biochemical and tageted sequencing approach is rapid, reliable, and cost-effective, making it a particularly valuable diagnostic option for families who cannot afford WES.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110596"},"PeriodicalIF":3.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007608","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}
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