Pub Date : 2025-08-05DOI: 10.1016/j.clim.2025.110575
Xing-Li Zhang , Meng-Meng Pan , Yaroslav Kaminskiy , Shi-Wei Jin , Jian-Qing Mi , Wei-Ping Zhang , Jie Xu
Autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) can cause engraftment syndrome (ES), a clinical diagnosis without specific laboratory biomarkers. Herein, six cytokines commonly elevated during transplantation were chronologically detected during ASCT in 96 patients with newly diagnosed MM, 24.0 % of whom experienced ES. Among the molecules demonstrating remarkable peak levels, only IL-5 was able to differentiate ES from non-ES. IL-5 measured on day 12 emerged as an optimal indicator of ES, and its diagnostic value was enhanced when combined with the proportion of endogenous CD8+ T cells after engraftment and daratumumab-naive history. Notably, IL-5 levels on day 6 (IL-5 D6) served as the earliest predictor. 70.8 % of the patients could be predicted as having ES or non-ES via the IL-5 D6 cutoff value and daratumumab treatment history. It suggests that IL-5 can aid in estimating ES, and prior exposure to daratumumab may reduce the incidence of ES.
{"title":"Interleukin-5 is an adjunctive biomarker for engraftment syndrome in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation","authors":"Xing-Li Zhang , Meng-Meng Pan , Yaroslav Kaminskiy , Shi-Wei Jin , Jian-Qing Mi , Wei-Ping Zhang , Jie Xu","doi":"10.1016/j.clim.2025.110575","DOIUrl":"10.1016/j.clim.2025.110575","url":null,"abstract":"<div><div>Autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) can cause engraftment syndrome (ES), a clinical diagnosis without specific laboratory biomarkers. Herein, six cytokines commonly elevated during transplantation were chronologically detected during ASCT in 96 patients with newly diagnosed MM, 24.0 % of whom experienced ES. Among the molecules demonstrating remarkable peak levels, only IL-5 was able to differentiate ES from non-ES. IL-5 measured on day 12 emerged as an optimal indicator of ES, and its diagnostic value was enhanced when combined with the proportion of endogenous CD8<sup>+</sup> T cells after engraftment and daratumumab-naive history. Notably, IL-5 levels on day 6 (IL-5 D6) served as the earliest predictor. 70.8 % of the patients could be predicted as having ES or non-ES via the IL-5 D6 cutoff value and daratumumab treatment history. It suggests that IL-5 can aid in estimating ES, and prior exposure to daratumumab may reduce the incidence of ES.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110575"},"PeriodicalIF":3.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774794","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 : 2025-07-26DOI: 10.1016/j.clim.2025.110574
Guhan Luo , Rong Ni , Xuanwei Huang , Yuanhui Li , Dingcun Luo
The SLAM family receptors are immunoglobulin superfamily receptors integral to immune cell communication and regulation. This review consolidates current knowledge on the structures and functions of SLAM family receptors members (SLAMF1–SLAMF9), emphasizing their roles within the tumor microenvironment. Notably, SLAMF7 has been extensively studied in multiple myeloma, serving as both a diagnostic marker and therapeutic target. Other SLAM family receptors are implicated in tumor immune evasion, drug resistance, and T-cell exhaustion. Emerging therapies, including monoclonal antibodies and combinations with immune checkpoint inhibitors, are evaluated. Despite promising findings, challenges such as functional redundancy and an incomplete understanding of the roles of SLAM family receptors across different cancer types persist. Ongoing research into their molecular mechanisms and clinical applications is essential for advancing effective cancer immunotherapies.
{"title":"The role of signaling lymphocytic activation molecule (SLAM) family receptors in health and disease progression: Focusing on cancer and therapy","authors":"Guhan Luo , Rong Ni , Xuanwei Huang , Yuanhui Li , Dingcun Luo","doi":"10.1016/j.clim.2025.110574","DOIUrl":"10.1016/j.clim.2025.110574","url":null,"abstract":"<div><div>The SLAM family receptors are immunoglobulin superfamily receptors integral to immune cell communication and regulation. This review consolidates current knowledge on the structures and functions of SLAM family receptors members (SLAMF1–SLAMF9), emphasizing their roles within the tumor microenvironment. Notably, SLAMF7 has been extensively studied in multiple myeloma, serving as both a diagnostic marker and therapeutic target. Other SLAM family receptors are implicated in tumor immune evasion, drug resistance, and T-cell exhaustion. Emerging therapies, including monoclonal antibodies and combinations with immune checkpoint inhibitors, are evaluated. Despite promising findings, challenges such as functional redundancy and an incomplete understanding of the roles of SLAM family receptors across different cancer types persist. Ongoing research into their molecular mechanisms and clinical applications is essential for advancing effective cancer immunotherapies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110574"},"PeriodicalIF":3.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723368","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 : 2025-07-23DOI: 10.1016/j.clim.2025.110572
Junhan Wu , Zhe He , Weitao Zhuang , Xin Xia , Zijie Li , Aotian Mo , Yizhang Chen , Rixin Chen , Guibin Qiao
Chronic inflammation is a crucial factor in the development and progression of lung cancer. External factors, such as indoor and outdoor air pollution and occupational hazards, along with imbalances in the lung microbiome, create a pro-inflammatory environment conducive to tumorigenesis. This review explores how various mechanisms drive the production of pro-inflammatory cytokines and immune modulators, leading to a tumor-promoting microenvironment. It also examines the roles of key cells in these processes and highlights the importance of epigenetic modifications in inflammation-driven lung cancer. Understanding these interactions provides insights into targeted therapeutic strategies and underscores the significance of addressing inflammation to reduce lung cancer risk.
{"title":"Mechanisms of inflammation-driven lung cancer: From external influences to internal regulation","authors":"Junhan Wu , Zhe He , Weitao Zhuang , Xin Xia , Zijie Li , Aotian Mo , Yizhang Chen , Rixin Chen , Guibin Qiao","doi":"10.1016/j.clim.2025.110572","DOIUrl":"10.1016/j.clim.2025.110572","url":null,"abstract":"<div><div>Chronic inflammation is a crucial factor in the development and progression of lung cancer. External factors, such as indoor and outdoor air pollution and occupational hazards, along with imbalances in the lung microbiome, create a pro-inflammatory environment conducive to tumorigenesis. This review explores how various mechanisms drive the production of pro-inflammatory cytokines and immune modulators, leading to a tumor-promoting microenvironment. It also examines the roles of key cells in these processes and highlights the importance of epigenetic modifications in inflammation-driven lung cancer. Understanding these interactions provides insights into targeted therapeutic strategies and underscores the significance of addressing inflammation to reduce lung cancer risk.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110572"},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717678","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}
Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic cancers. Cytokines play an important role in the regulation of normal and pathologic hematopoiesis. A pro-inflammatory state, described in hematopoietic malignancies, may participate in clonal selection. To identify recurrent cytokine patterns according to AML ontogenic subtypes, we quantified the concentration of 49 cytokines in the bone marrow (BM) plasma from 124 patients with AML or myelodysplastic syndrome (MDS), and from 94 healthy volunteers. We confirmed a pro-inflammatory profile in MDS and AML, with increased concentrations of CXCL8, CXCL10 and IL-6. Only a few cytokines varied when comparing AML to MDS. De novo AML subtypes carry a specific cytokine pattern dominated by the increase in CLEC11A concentrations and the decrease in FLT3 ligand concentrations. These cytokines could participate in clonal selection in this subtype of AML while being less critical in the other AMLs - i.e. secondary-like or TP53-mutated subtypes.
{"title":"A specific bone marrow cytokine pattern in de novo acute myeloid leukemia","authors":"Noémie Ravalet , Hélène Guermouche , Pierre Hirsch , Frédéric Picou , Vincent Flament , Caroline Deswarte , Amélie Foucault , Jenny Beaud , Emmanuelle Rault , Emeline Saindoy , Sébastien Lachot , Mara Memoli , Nawa Hachem , Jean-Alain Martignoles , Valérie Gissot , Ludovic Suner , Emmanuel Gyan , Ollivier Legrand , Olivier Hérault , François Delhommeau","doi":"10.1016/j.clim.2025.110573","DOIUrl":"10.1016/j.clim.2025.110573","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic cancers. Cytokines play an important role in the regulation of normal and pathologic hematopoiesis. A pro-inflammatory state, described in hematopoietic malignancies, may participate in clonal selection. To identify recurrent cytokine patterns according to AML ontogenic subtypes, we quantified the concentration of 49 cytokines in the bone marrow (BM) plasma from 124 patients with AML or myelodysplastic syndrome (MDS), and from 94 healthy volunteers. We confirmed a pro-inflammatory profile in MDS and AML, with increased concentrations of CXCL8, CXCL10 and IL-6. Only a few cytokines varied when comparing AML to MDS. <em>De novo</em> AML subtypes carry a specific cytokine pattern dominated by the increase in CLEC11A concentrations and the decrease in FLT3 ligand concentrations. These cytokines could participate in clonal selection in this subtype of AML while being less critical in the other AMLs - <em>i.e.</em> secondary-like or <em>TP53-</em>mutated subtypes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110573"},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712889","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 : 2025-07-21DOI: 10.1016/j.clim.2025.110571
Anjali S. Yennemadi , Natasha Jordan , Sophie Diong , Mark Little , Joseph Keane , Gina Leisching
Background
Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses linked to immunometabolic perturbations. While mitochondrial dysfunction has been implicated in SLE, its cell-type-specific impact on immune subsets remains underexplored.
Methods
We repurposed existing RNA-seq data from SLE patient peripheral blood mononuclear cells, with a focus on nuclear-encoded mitochondrial (NEmt) genes, as well as mitochondrial genes themselves, to identify differentially expressed genes compared to healthy controls. Mitochondrial stress tests were performed on freshly isolated CD4+ T cells, CD8+ T cells, B cells, and monocytes from SLE patients and healthy donors to assess bioenergetic function.
Results
RNA-seq revealed that both NEmt genes and mitochondrial genes were downregulated in the PBMC population of SLE patients. In situ mitochondrial stress tests revealed significant reductions in oxygen consumption rate (OCR), indicating impaired oxidative phosphorylation (OXPHOS) across all immune subsets, while extracellular acidification rate (ECAR), a marker of glycolysis, remained unchanged. These findings highlight immune-cell-specific mitochondrial bioenergetic failure in SLE, without compensatory glycolytic adaptation.
Conclusion
Our results position mitochondrial fitness as a novel therapeutic target in SLE. We propose leveraging high-throughput screening of mitochondria-targeted compounds, including FDA-approved agents, to enhance OXPHOS, regulate mitophagy, or mitigate oxidative stress. This precision-based approach offers a paradigm shift from conventional immunosuppression to metabolic recalibration, with the potential to restore immune homeostasis in SLE.
Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses linked to immunometabolic perturbations. While mitochondrial dysfunction has been implicated in SLE, its cell-type-specific impact on immune subsets remains underexplored.Using existing RNA-seq data we focused on nuclear-encoded mitochondrial (NEmt) genes, as well as mitochondrial genes themselves. Mitochondrial stress tests were performed on freshly isolated CD4+ T cells, CD8+ T cells, B cells, and monocytes from SLE patients and healthy donors to assess bioenergetic function.RNA-seq revealed that both NEmt genes and mitochondrial genes were downregulated in the PBMC population of SLE patients. In situ mitochondrial stress tests revealed significant reductions in oxygen consumption rate, indicating impaired oxidative phosphorylation across all immune subsets, while glycolysis remained unchanged. These findings highlight immune-cell-specific bioenergetic failure in SLE and propose mitochondrial fitness as a novel therapeutic target in SLE. This precision-based approach offers a paradigm shift from conventional immunosuppression to metabolic recalibration.
{"title":"Mitochondrial bioenergetic failure in SLE immunocytes: Targeting fitness for therapy","authors":"Anjali S. Yennemadi , Natasha Jordan , Sophie Diong , Mark Little , Joseph Keane , Gina Leisching","doi":"10.1016/j.clim.2025.110571","DOIUrl":"10.1016/j.clim.2025.110571","url":null,"abstract":"<div><h3>Background</h3><div>Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses linked to immunometabolic perturbations. While mitochondrial dysfunction has been implicated in SLE, its cell-type-specific impact on immune subsets remains underexplored.</div></div><div><h3>Methods</h3><div>We repurposed existing RNA-seq data from SLE patient peripheral blood mononuclear cells, with a focus on nuclear-encoded mitochondrial (NEmt) genes, as well as mitochondrial genes themselves, to identify differentially expressed genes compared to healthy controls. Mitochondrial stress tests were performed on freshly isolated CD4+ T cells, CD8+ T cells, B cells, and monocytes from SLE patients and healthy donors to assess bioenergetic function.</div></div><div><h3>Results</h3><div>RNA-seq revealed that both NEmt genes and mitochondrial genes were downregulated in the PBMC population of SLE patients. In situ mitochondrial stress tests revealed significant reductions in oxygen consumption rate (OCR), indicating impaired oxidative phosphorylation (OXPHOS) across all immune subsets, while extracellular acidification rate (ECAR), a marker of glycolysis, remained unchanged. These findings highlight immune-cell-specific mitochondrial bioenergetic failure in SLE, without compensatory glycolytic adaptation.</div></div><div><h3>Conclusion</h3><div>Our results position mitochondrial fitness as a novel therapeutic target in SLE. We propose leveraging high-throughput screening of mitochondria-targeted compounds, including FDA-approved agents, to enhance OXPHOS, regulate mitophagy, or mitigate oxidative stress. This precision-based approach offers a paradigm shift from conventional immunosuppression to metabolic recalibration, with the potential to restore immune homeostasis in SLE.</div><div>Systemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses linked to immunometabolic perturbations. While mitochondrial dysfunction has been implicated in SLE, its cell-type-specific impact on immune subsets remains underexplored.Using existing RNA-seq data we focused on nuclear-encoded mitochondrial (NEmt) genes, as well as mitochondrial genes themselves. Mitochondrial stress tests were performed on freshly isolated CD4+ T cells, CD8+ T cells, B cells, and monocytes from SLE patients and healthy donors to assess bioenergetic function.RNA-seq revealed that both NEmt genes and mitochondrial genes were downregulated in the PBMC population of SLE patients. In situ mitochondrial stress tests revealed significant reductions in oxygen consumption rate, indicating impaired oxidative phosphorylation across all immune subsets, while glycolysis remained unchanged. These findings highlight immune-cell-specific bioenergetic failure in SLE and propose mitochondrial fitness as a novel therapeutic target in SLE. This precision-based approach offers a paradigm shift from conventional immunosuppression to metabolic recalibration.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110571"},"PeriodicalIF":4.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686316","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 : 2025-07-20DOI: 10.1016/j.clim.2025.110568
Yang Liu , Sumiao Liu , Ying Liu, Qian Li, Ke Xu
Objectives
To evaluate infection risk associated with hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).
Methods
We retrospectively analyzed 242 cases of hypogammaglobulinemia identified among 3565 hospitalized SLE patients between 2014 and 2024. Of these, 133 experienced infections, while 109 remained infection-free and served as controls.
Results
Infection rates were comparable among patients with low IgG (60.0 %), IgM (56.3 %) and IgA (57.7 %) levels. Multivariate logistic regression identified low body weight, fever, medication discontinuation, lymphopenia, reduced lymphocyte count, elevated CRP levels, and decreased Th cell and NK cell counts as independent predictors of infection. During follow-up, immunoglobulin levels recovered in most patients, with rates at two years of 76.0 % for IgA, 43.8 % for IgG, and 26.2 % for IgM. Immunoglobulin normalization was associated with reduced infection risk.
Conclusion
Hypogammaglobulinemia increases infection risk in SLE due to multifactorial immune dysfunction. Modifiable clinical and immunologic factors, along with immunoglobulin recovery, may represent actionable targets for intervention.
{"title":"Infection risk associated with hypogammaglobulinemia in patients with systemic lupus erythematosus: Real-world evidence from 2014 to 2024","authors":"Yang Liu , Sumiao Liu , Ying Liu, Qian Li, Ke Xu","doi":"10.1016/j.clim.2025.110568","DOIUrl":"10.1016/j.clim.2025.110568","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate infection risk associated with hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 242 cases of hypogammaglobulinemia identified among 3565 hospitalized SLE patients between 2014 and 2024. Of these, 133 experienced infections, while 109 remained infection-free and served as controls.</div></div><div><h3>Results</h3><div>Infection rates were comparable among patients with low IgG (60.0 %), IgM (56.3 %) and IgA (57.7 %) levels. Multivariate logistic regression identified low body weight, fever, medication discontinuation, lymphopenia, reduced lymphocyte count, elevated CRP levels, and decreased Th cell and NK cell counts as independent predictors of infection. During follow-up, immunoglobulin levels recovered in most patients, with rates at two years of 76.0 % for IgA, 43.8 % for IgG, and 26.2 % for IgM. Immunoglobulin normalization was associated with reduced infection risk.</div></div><div><h3>Conclusion</h3><div>Hypogammaglobulinemia increases infection risk in SLE due to multifactorial immune dysfunction. Modifiable clinical and immunologic factors, along with immunoglobulin recovery, may represent actionable targets for intervention.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110568"},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686317","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}
Ferroptosis is an iron-dependent cell death characterized by elevated levels of reactive oxygen species (ROS) and the peroxidation of membrane lipids, leading to cellular destruction. This phenomenon results from a disruption in the balance between oxidative and antioxidative processes, with oxidation involving iron and lipid metabolism, and antioxidation primarily relying on GPX4. Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled plasma cell growth, accounting for 1.3 % of all malignancies. Despite advancements in treatment, MM still has a poor prognosis. Research indicates that malignant MM cells are susceptible to ferroptosis, suggesting that this process may serve as a novel therapeutic strategy to enhance the efficacy of treatment for MM. This review explores current insights into the cellular mechanisms of ferroptosis and its role in eliminating multiple myeloma cells, as well as its effectiveness alongside conventional drugs like Bortezomib.
{"title":"Iron-dependent cell death: Unlocking Ferroptosis as a key to multiple myeloma therapy","authors":"Fatemeh Karimian , Melika Khademi , Amirsalar Nikkhah Bahrami , Maryam Nabigol , Fatemeh Mikanik , Mehdi Bakhtiyaridovvombaygi , Nader Vazifeh Shiran","doi":"10.1016/j.clim.2025.110570","DOIUrl":"10.1016/j.clim.2025.110570","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent cell death characterized by elevated levels of reactive oxygen species (ROS) and the peroxidation of membrane lipids, leading to cellular destruction. This phenomenon results from a disruption in the balance between oxidative and antioxidative processes, with oxidation involving iron and lipid metabolism, and antioxidation primarily relying on GPX4. Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled plasma cell growth, accounting for 1.3 % of all malignancies. Despite advancements in treatment, MM still has a poor prognosis. Research indicates that malignant MM cells are susceptible to ferroptosis, suggesting that this process may serve as a novel therapeutic strategy to enhance the efficacy of treatment for MM. This review explores current insights into the cellular mechanisms of ferroptosis and its role in eliminating multiple myeloma cells, as well as its effectiveness alongside conventional drugs like Bortezomib.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110570"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667246","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 : 2025-07-11DOI: 10.1016/j.clim.2025.110563
Fatima Zaman , Xianming Zhu , Joanne H. Hunt , Gracie Rozek , Yolanda Eby , Sarah Hussain , Niraj M. Desai , Sander Florman , Meenakshi M. Rana , Rachel Friedman-Moraco , Marcus R. Pereira , Shikha Mehta , Peter Stock , Alexander Gilbert , Jonathan Hand , Michele I. Morris , Valentina Stosor , Sapna A. Mehta , Catherine B. Small , Joanna Schaenman , Aaron A.R. Tobian
Kidney transplantation from donors with HIV has recently become standard clinical practice, but the plasma inflammatory profile is not well characterized. Thirty-two cytokines and chemokines were evaluated among donors with HIV (n = 63) and without HIV (n = 41). Wilcoxon rank sum test was used to compare cytokines between groups. Donors with and without HIV were generally similar in terms of characteristics, except those with HIV had a non-significantly lower kidney donor profile index, reflecting better graft survival, creatinine, and body mass index. Most cytokine and chemokine levels were similar between groups. However, median IL-8 levels were higher (p < 0.0015) in donors without HIV (32.6 pg/mL, IQR = 13.8–394.9) compared to donors with HIV (15.1 pg/mL, IQR = 8.4–35.5). There were no significant correlations between cytokine and chemokine concentrations and CD4 counts or HIV viral load. In summary, inflammatory profiles were similar or lower among donors with HIV compared to donors without HIV supporting the safety of this emerging kidney transplantation practice.
{"title":"Inflammation among kidney transplant donors with and without HIV: Multicenter HOPE in Action Consortium","authors":"Fatima Zaman , Xianming Zhu , Joanne H. Hunt , Gracie Rozek , Yolanda Eby , Sarah Hussain , Niraj M. Desai , Sander Florman , Meenakshi M. Rana , Rachel Friedman-Moraco , Marcus R. Pereira , Shikha Mehta , Peter Stock , Alexander Gilbert , Jonathan Hand , Michele I. Morris , Valentina Stosor , Sapna A. Mehta , Catherine B. Small , Joanna Schaenman , Aaron A.R. Tobian","doi":"10.1016/j.clim.2025.110563","DOIUrl":"10.1016/j.clim.2025.110563","url":null,"abstract":"<div><div>Kidney transplantation from donors with HIV has recently become standard clinical practice, but the plasma inflammatory profile is not well characterized. Thirty-two cytokines and chemokines were evaluated among donors with HIV (<em>n</em> = 63) and without HIV (<em>n</em> = 41). Wilcoxon rank sum test was used to compare cytokines between groups. Donors with and without HIV were generally similar in terms of characteristics, except those with HIV had a non-significantly lower kidney donor profile index, reflecting better graft survival, creatinine, and body mass index. Most cytokine and chemokine levels were similar between groups. However, median IL-8 levels were higher (<em>p</em> < 0.0015) in donors without HIV (32.6 pg/mL, IQR = 13.8–394.9) compared to donors with HIV (15.1 pg/mL, IQR = 8.4–35.5). There were no significant correlations between cytokine and chemokine concentrations and CD4 counts or HIV viral load. In summary, inflammatory profiles were similar or lower among donors with HIV compared to donors without HIV supporting the safety of this emerging kidney transplantation practice.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110563"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625481","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 : 2025-07-11DOI: 10.1016/j.clim.2025.110564
Johanna Bodin , Anja Bråthen Kristoffersen , Tove Karin Herstad , Gro Tunheim , Sabin Bhandari , Anna Hayman Robertson , Ratnadeep Mukherjee , Unni Cecilie Nygaard , Fredrik Oftung , Lisbeth M. Næss
While severe COVID-19 is well-characterized, immune profiles of non-hospitalized, non-vaccinated individuals are less investigated. High-dimensional single-cell profiling and multiplex serum marker analysis characterized immune profiles according to outcome during acute infection and six months later. Lower IL-1RA and HGF levels, higher CD57+TIGIT+NKT, CD57+GrB+NKT, CD16+TIGIT+NK and CD4+CD57+GrB+ effector T-cell levels characterized asymptomatic infection. PMA + ionomycin induced higher frequencies of polyfunctional CD4+ and CD8+ effector T-cells in asymptomatic compared to moderate disease. Absence of multiple long-term symptoms was associated with higher CD16+TIGIT+NK-cell frequency, lower HGF levels and persisting high memory B and regulatory NK subpopulation levels. Higher frequency of CD16+TIGIT+ NK cells was in common for non-infected, asymptomatic, and individuals without multiple long-term symptoms. Compared to infected individuals, non-infected cases showed higher pre-existing T-cell responses to hCoV and SARS-CoV-2 peptides. This study contributes to increased understanding of protective immune responses in non-hospitalized COVID-19 cases, emphasizing the role of defined NK and T-cell subpopulations.
{"title":"High-dimensional immune profiling identifies circulating NK and T cell subpopulations associated with asymptomatic COVID-19 and absence of multiple long-term symptoms","authors":"Johanna Bodin , Anja Bråthen Kristoffersen , Tove Karin Herstad , Gro Tunheim , Sabin Bhandari , Anna Hayman Robertson , Ratnadeep Mukherjee , Unni Cecilie Nygaard , Fredrik Oftung , Lisbeth M. Næss","doi":"10.1016/j.clim.2025.110564","DOIUrl":"10.1016/j.clim.2025.110564","url":null,"abstract":"<div><div>While severe COVID-19 is well-characterized, immune profiles of non-hospitalized, non-vaccinated individuals are less investigated. High-dimensional single-cell profiling and multiplex serum marker analysis characterized immune profiles according to outcome during acute infection and six months later. Lower IL-1RA and HGF levels, higher CD57<sup>+</sup>TIGIT<sup>+</sup>NKT, CD57<sup>+</sup>GrB<sup>+</sup>NKT, CD16<sup>+</sup>TIGIT<sup>+</sup>NK and CD4<sup>+</sup>CD57<sup>+</sup>GrB<sup>+</sup> effector T-cell levels characterized asymptomatic infection. PMA + ionomycin induced higher frequencies of polyfunctional CD4<sup>+</sup> and CD8<sup>+</sup> effector T-cells in asymptomatic compared to moderate disease. Absence of multiple long-term symptoms was associated with higher CD16<sup>+</sup>TIGIT<sup>+</sup>NK-cell frequency, lower HGF levels and persisting high memory B and regulatory NK subpopulation levels. Higher frequency of CD16<sup>+</sup>TIGIT<sup>+</sup> NK cells was in common for non-infected, asymptomatic, and individuals without multiple long-term symptoms. Compared to infected individuals, non-infected cases showed higher pre-existing T-cell responses to hCoV and SARS-CoV-2 peptides. This study contributes to increased understanding of protective immune responses in non-hospitalized COVID-19 cases, emphasizing the role of defined NK and T-cell subpopulations.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110564"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625480","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}
Human Herpesvirus 8 (HHV-8) poses a significant risk in solid organ transplant recipients (SOTRs). HHV-8 is implicated in both neoplastic and non-neoplastic conditions. This study investigates immune dysregulation in HHV-8-infected SOTRs by analysing cytokine profiles and virus-specific T cell responses across different clinical manifestations. Our findings reveal a progressive decline in HHV-8-specific T cell responses correlating with disease severity, alongside a distinct cytokine signature. KICS patients exhibit heightened inflammation with elevated IL-6, IL-10, IFNα, TNFα, IL-1β, IL-17 A, IDO, sCD14, and immune exhaustion markers (PD-1, LAG-3), whereas KS is associated with angiogenic and macrophage activation factors (HGF, CD163). Given these insights, monitoring HHV-8 DNAemia, inflammatory cytokines, and T cell functionality is crucial for early detection and risk stratification. This study underscores the importance of immune monitoring in transplant recipients, paving the way for targeted interventions to mitigate HHV-8-associated complications.
{"title":"Immune profiling in solid organ transplant recipients with HHV-8 infection: Identification of immunological biomarkers for KICS and Kaposi's sarcoma","authors":"Rosalia Busà , Francesca Timoneri , Monica Miele , Mariangela Di Bella , Andrea Cona , Salvatore Castelbuono , Mattia Emanuela Ligotti , Alessia Gallo , Francesca Pecoraro , Giuseppe Randazzo , Caterina Amato , Clara Pipia , Giandomenico Amico , Valentina Agnese , Pier Giulio Conaldi , Mario Luppi , Alessandra Mularoni , Matteo Bulati","doi":"10.1016/j.clim.2025.110562","DOIUrl":"10.1016/j.clim.2025.110562","url":null,"abstract":"<div><div>Human Herpesvirus 8 (HHV-8) poses a significant risk in solid organ transplant recipients (SOTRs). HHV-8 is implicated in both neoplastic and non-neoplastic conditions. This study investigates immune dysregulation in HHV-8-infected SOTRs by analysing cytokine profiles and virus-specific T cell responses across different clinical manifestations. Our findings reveal a progressive decline in HHV-8-specific T cell responses correlating with disease severity, alongside a distinct cytokine signature. KICS patients exhibit heightened inflammation with elevated IL-6, IL-10, IFNα, TNFα, IL-1β, IL-17 A, IDO, sCD14, and immune exhaustion markers (PD-1, LAG-3), whereas KS is associated with angiogenic and macrophage activation factors (HGF, CD163). Given these insights, monitoring HHV-8 DNAemia, inflammatory cytokines, and T cell functionality is crucial for early detection and risk stratification. This study underscores the importance of immune monitoring in transplant recipients, paving the way for targeted interventions to mitigate HHV-8-associated complications.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"280 ","pages":"Article 110562"},"PeriodicalIF":4.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604458","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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