Pub Date : 2025-03-06DOI: 10.1016/j.imlet.2025.106992
Valentina Artusa , Lara De Luca , Mario Clerici , Daria Trabattoni
Mitochondria are more than mere energy generators; they are multifaceted organelles that integrate metabolic, signalling, and immune functions, making them indispensable players in maintaining cellular and systemic health. Mitochondrial transfer has recently garnered attention due to its potential role in several physiological and pathological processes. This process involves multiple mechanisms by which mitochondria, along with mitochondrial DNA and other components, are exchanged between cells. In this review, we examine the critical roles of mitochondrial transfer in health and disease, focusing on its impact on immune cell function, the resolution of inflammation, tissue repair, and regeneration. Additionally, we explore its implications in viral infections and cancer progression. We also provide insights into emerging therapeutic applications, emphasizing its potential to address unmet clinical needs.
{"title":"Connecting the dots: Mitochondrial transfer in immunity, inflammation, and cancer","authors":"Valentina Artusa , Lara De Luca , Mario Clerici , Daria Trabattoni","doi":"10.1016/j.imlet.2025.106992","DOIUrl":"10.1016/j.imlet.2025.106992","url":null,"abstract":"<div><div>Mitochondria are more than mere energy generators; they are multifaceted organelles that integrate metabolic, signalling, and immune functions, making them indispensable players in maintaining cellular and systemic health. Mitochondrial transfer has recently garnered attention due to its potential role in several physiological and pathological processes. This process involves multiple mechanisms by which mitochondria, along with mitochondrial DNA and other components, are exchanged between cells. In this review, we examine the critical roles of mitochondrial transfer in health and disease, focusing on its impact on immune cell function, the resolution of inflammation, tissue repair, and regeneration. Additionally, we explore its implications in viral infections and cancer progression. We also provide insights into emerging therapeutic applications, emphasizing its potential to address unmet clinical needs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"274 ","pages":"Article 106992"},"PeriodicalIF":3.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.imlet.2025.106993
Xiang Zhang , Shouci Hu , Puchang Luo , Zhiyu Li , Zhejun Chen , Cong Xia , Linxuan Fan , Rongqun Li , Hongbo Chen
The development of systemic lupus erythematosus (SLE) involves both genetic and environmental factors. Epstein–Barr virus (EBV) infection has been implicated in SLE pathogenesis, particularly through the activity of latent membrane protein 1 (LMP-1). This study aimed to explore the role of LMP-1 in regulating susceptibility gene expression in SLE. Peripheral blood mononuclear cells (PBMCs) from SLE patients and H9 T cells were used to investigate this mechanism both in vivo and in vitro. RNA-seq analysis revealed that LMP-1 and the SLE susceptibility gene AT-rich interactive domain 5B (ARID5B) were significantly upregulated in SLE. Overexpression of LMP-1 in H9 T cells further increased ARID5B expression. Histone H3K27 methylation, catalyzed by enhancer of zeste homolog 2 (EZH2), was significantly elevated, suggesting epigenetic modifications play a role in this regulation. H3K27 methylation was studied due to its known involvement in transcriptional repression and chromatin remodeling in autoimmune diseases. Furthermore, phosphorylated p65 (p-p65), a marker of nuclear factor-kappa-B (NF-κB) pathway activation, was increased. Blocking the NF-κB signaling pathway reduced ARID5B expression, indicating that LMP-1 may regulate susceptibility genes through NF-κB signaling and histone modifications. These findings suggest that EBV LMP-1 contributes to SLE pathogenesis by epigenetically modulating susceptibility gene expression and activating inflammatory pathways.
{"title":"The regulatory effect and molecular mechanism of Epstein-Barr virus protein LMP-1 in SLE susceptibility gene expression","authors":"Xiang Zhang , Shouci Hu , Puchang Luo , Zhiyu Li , Zhejun Chen , Cong Xia , Linxuan Fan , Rongqun Li , Hongbo Chen","doi":"10.1016/j.imlet.2025.106993","DOIUrl":"10.1016/j.imlet.2025.106993","url":null,"abstract":"<div><div>The development of systemic lupus erythematosus (SLE) involves both genetic and environmental factors. Epstein–Barr virus (EBV) infection has been implicated in SLE pathogenesis, particularly through the activity of latent membrane protein 1 (LMP-1). This study aimed to explore the role of LMP-1 in regulating susceptibility gene expression in SLE. Peripheral blood mononuclear cells (PBMCs) from SLE patients and H9 T cells were used to investigate this mechanism both in vivo and in vitro. RNA-seq analysis revealed that LMP-1 and the SLE susceptibility gene AT-rich interactive domain 5B (ARID5B) were significantly upregulated in SLE. Overexpression of LMP-1 in H9 T cells further increased ARID5B expression. Histone H3K27 methylation, catalyzed by enhancer of zeste homolog 2 (EZH2), was significantly elevated, suggesting epigenetic modifications play a role in this regulation. H3K27 methylation was studied due to its known involvement in transcriptional repression and chromatin remodeling in autoimmune diseases. Furthermore, phosphorylated p65 (p-p65), a marker of nuclear factor-kappa-B (NF-κB) pathway activation, was increased. Blocking the NF-κB signaling pathway reduced ARID5B expression, indicating that LMP-1 may regulate susceptibility genes through NF-κB signaling and histone modifications. These findings suggest that EBV LMP-1 contributes to SLE pathogenesis by epigenetically modulating susceptibility gene expression and activating inflammatory pathways.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106993"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534183","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 : 2025-02-20DOI: 10.1016/j.imlet.2025.106990
Zhihao Liu , Jing Hu , Xingzhi Han , Li Li , Haiqing Niu , Xin Zhang , Ning Wang , Xiao Shi , Liuqi Sang , Qun Zhang , Xiaoping Qian
Emerging studies have demonstrated that phagocytosis checkpoints, which promote tumor-mediated immune evasion, are potential targets for cancer immunotherapy. In this study, the TCGA colorectal cancer (CRC) dataset and our RNA sequencing dataset suggested that SLAMF8 expression is significantly positively correlated with the expression levels of multiple phagocytosis checkpoint molecules. In vitro, we confirmed that SLAMF8 significantly regulated the phagocytosis of mouse CRC cells. RNA sequencing revealed that the expression of genes that promote Fc receptor (FcR)-mediated phagocytosis, such as FCGR1, FCGR3, FCGR2b, FCGR4, and ITGAM, was significantly upregulated after SLAMF8 knockdown. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that the significantly enriched signaling pathways after SLAMF8 knockdown or overexpression included the PI3K-Akt signaling pathway. The protein expression levels of p-PI3K and p-Akt were significantly increased after SLAMF8 knockdown. When PI3K inhibitors and Fc blockers were added after SLAMF8 knockdown, mouse macrophage phagocytosis, and FcR expression decreased. Our results suggest that SLAMF8 may impair FcR-mediated phagocytosis through the PI3K-Akt signaling pathway and negatively regulate the antitumor immune response.
{"title":"SLAMF8 regulates Fc receptor-mediated phagocytosis in mouse macrophage cells through PI3K-Akt signaling","authors":"Zhihao Liu , Jing Hu , Xingzhi Han , Li Li , Haiqing Niu , Xin Zhang , Ning Wang , Xiao Shi , Liuqi Sang , Qun Zhang , Xiaoping Qian","doi":"10.1016/j.imlet.2025.106990","DOIUrl":"10.1016/j.imlet.2025.106990","url":null,"abstract":"<div><div>Emerging studies have demonstrated that phagocytosis checkpoints, which promote tumor-mediated immune evasion, are potential targets for cancer immunotherapy. In this study, the TCGA colorectal cancer (CRC) dataset and our RNA sequencing dataset suggested that <em>SLAMF8</em> expression is significantly positively correlated with the expression levels of multiple phagocytosis checkpoint molecules. In vitro, we confirmed that <em>SLAMF8</em> significantly regulated the phagocytosis of mouse CRC cells. RNA sequencing revealed that the expression of genes that promote Fc receptor (FcR)-mediated phagocytosis, such as FCGR1, FCGR3, FCGR2b, FCGR4, and ITGAM, was significantly upregulated after <em>SLAMF8</em> knockdown. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results suggested that the significantly enriched signaling pathways after <em>SLAMF8</em> knockdown or overexpression included the PI3K-Akt signaling pathway. The protein expression levels of p-PI3K and p-Akt were significantly increased after <em>SLAMF8</em> knockdown. When PI3K inhibitors and Fc blockers were added after <em>SLAMF8</em> knockdown, mouse macrophage phagocytosis, and FcR expression decreased. Our results suggest that <em>SLAMF8</em> may impair FcR-mediated phagocytosis through the PI3K-Akt signaling pathway and negatively regulate the antitumor immune response.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106990"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445941","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}
Neutrophils, the most abundant leukocytes in circulation, have become the subject of intensive research due to growing evidence of their role as modulators of cancer with both anti- and pro-tumorigenic effects. However, their prognostic function related to the release of neutrophil extracellular traps (NETs) and production of reactive oxygen species (ROS) has not yet been elucidated in the context of bladder cancer (BC). This study aimed to evaluate the ability of circulating neutrophils from BC patients to undergo NETosis and produce ROS—both spontaneously and following activation with phorbol 12-myristate 13-acetate (PMA)—using flow cytometry and immunofluorescence techniques. Their relevance to clinicopathological characteristics was also evaluated. Our results showed that PMA-treated neutrophils had increased early NETosis in patients with stage II (P = 0.048) and T2 (P = 0.014) compared to those with stage III and T3, respectively. These cells also showed a significant increase in ROS production in patients with T2 compared to those with T3 (P = 0.026) and T4 (P = 0.014), as well as in patients with stage II compared to stage IV (P = 0.048). Additionally, spontaneous ROS production was higher in patients without lymphovascular invasion than in those with invasion (P = 0.013). The increased activity of neutrophils observed in earlier stages (stage II and T2) suggests a potential protective mechanism in the early phases of cancer progression. It also highlights NETosis and ROS production by neutrophils as possible biomarkers for assessing disease progression. These findings provide insights into the complex interactions of neutrophils within the tumor microenvironment and lay the groundwork for further investigations into targeted therapies, potentially improving prognostic evaluations and treatment outcomes for patients.
{"title":"Neutrophil extracellular traps and reactive oxygen species: Predictors of prognosis in bladder cancer","authors":"Zahra Mansourabadi , Mohammad-Ali Assarehzadegan , Fereshteh Mehdipour , Ali Ariafar , Zahra Faghih , Elahe Safari","doi":"10.1016/j.imlet.2025.106991","DOIUrl":"10.1016/j.imlet.2025.106991","url":null,"abstract":"<div><div>Neutrophils, the most abundant leukocytes in circulation, have become the subject of intensive research due to growing evidence of their role as modulators of cancer with both anti- and pro-tumorigenic effects. However, their prognostic function related to the release of neutrophil extracellular traps (NETs) and production of reactive oxygen species (ROS) has not yet been elucidated in the context of bladder cancer (BC). This study aimed to evaluate the ability of circulating neutrophils from BC patients to undergo NETosis and produce ROS—both spontaneously and following activation with phorbol 12-myristate 13-acetate (PMA)—using flow cytometry and immunofluorescence techniques. Their relevance to clinicopathological characteristics was also evaluated. Our results showed that PMA-treated neutrophils had increased early NETosis in patients with stage II (<em>P</em> = 0.048) and T2 (<em>P</em> = 0.014) compared to those with stage III and T3, respectively. These cells also showed a significant increase in ROS production in patients with T2 compared to those with T3 (<em>P</em> = 0.026) and T4 (<em>P</em> = 0.014), as well as in patients with stage II compared to stage IV (<em>P</em> = 0.048). Additionally, spontaneous ROS production was higher in patients without lymphovascular invasion than in those with invasion (<em>P</em> = 0.013). The increased activity of neutrophils observed in earlier stages (stage II and T2) suggests a potential protective mechanism in the early phases of cancer progression. It also highlights NETosis and ROS production by neutrophils as possible biomarkers for assessing disease progression. These findings provide insights into the complex interactions of neutrophils within the tumor microenvironment and lay the groundwork for further investigations into targeted therapies, potentially improving prognostic evaluations and treatment outcomes for patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106991"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457983","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 : 2025-02-16DOI: 10.1016/j.imlet.2025.106982
Zhiyong Liu, Aichun Chu, Zhiqian Bai, Chao Yang
Background: Gouty arthritis (GA) is a common rheumatic disease caused by the release of monosodium urate crystal (MSU) deposits into joint space. Nobiletin is a polymethoxylated flavonoid isolated from citrus fruits and has many beneficial activities. This study aimed to elucidate the therapeutic efficacy of nobiletin in GA and to reveal its potential mechanisms.
Methods: Phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 macrophages were primed with lipopolysaccharide (LPS) and then stimulated with MSU crystals in the presence or absence of nobiletin. Cell viability as well as the levels of proinflammatory cytokines, pathway-related proteins, NLRP3 inflammasomes, and autophagy-related proteins were evaluated. MSU was used to induce GA in mice. Hematoxylin-eosin staining was conducted to assess histological morphology changes. Immunofluorescence staining was performed to measure LC3 expression in THP-1 cells and ankle joint tissues.
Results: For in vitro analysis, nobiletin reduced LPS and MSU-induced cell viability inhibition. Additionally, nobiletin inhibited inflammation and NF-κB/NLRP3 pathway in THP-1 cells. Moreover, nobiletin inhibited the activation of NLRP3 inflammasome by promoting AMPK/mTOR-mediated autophagy. For in vivo analysis, nobiletin attenuated MSU-induced GA in mice. Additionally, nobiletin suppressed inflammation and NF-κB/NLRP3 pathway and promoted tissue autophagy in GA mice.
Conclusion: Nobiletin prevents MSU-induced GA in mice by inhibiting NF-κB/NLRP3 inflammasome activation through AMPK/mTOR-mediated autophagy.
{"title":"Nobiletin ameliorates monosodium urate-induced gouty arthritis in mice by enhancing AMPK/mTOR-mediated autophagy to inhibit NF-κB/NLRP3 inflammasome activation.","authors":"Zhiyong Liu, Aichun Chu, Zhiqian Bai, Chao Yang","doi":"10.1016/j.imlet.2025.106982","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.106982","url":null,"abstract":"<p><strong>Background: </strong>Gouty arthritis (GA) is a common rheumatic disease caused by the release of monosodium urate crystal (MSU) deposits into joint space. Nobiletin is a polymethoxylated flavonoid isolated from citrus fruits and has many beneficial activities. This study aimed to elucidate the therapeutic efficacy of nobiletin in GA and to reveal its potential mechanisms.</p><p><strong>Methods: </strong>Phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 macrophages were primed with lipopolysaccharide (LPS) and then stimulated with MSU crystals in the presence or absence of nobiletin. Cell viability as well as the levels of proinflammatory cytokines, pathway-related proteins, NLRP3 inflammasomes, and autophagy-related proteins were evaluated. MSU was used to induce GA in mice. Hematoxylin-eosin staining was conducted to assess histological morphology changes. Immunofluorescence staining was performed to measure LC3 expression in THP-1 cells and ankle joint tissues.</p><p><strong>Results: </strong>For in vitro analysis, nobiletin reduced LPS and MSU-induced cell viability inhibition. Additionally, nobiletin inhibited inflammation and NF-κB/NLRP3 pathway in THP-1 cells. Moreover, nobiletin inhibited the activation of NLRP3 inflammasome by promoting AMPK/mTOR-mediated autophagy. For in vivo analysis, nobiletin attenuated MSU-induced GA in mice. Additionally, nobiletin suppressed inflammation and NF-κB/NLRP3 pathway and promoted tissue autophagy in GA mice.</p><p><strong>Conclusion: </strong>Nobiletin prevents MSU-induced GA in mice by inhibiting NF-κB/NLRP3 inflammasome activation through AMPK/mTOR-mediated autophagy.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"106982"},"PeriodicalIF":3.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448939","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 : 2025-02-12DOI: 10.1016/j.imlet.2025.106981
Yan Wang , Hailin Mu , Baochen Yang , Chang Yang, Wei Dong, Jiawei Wang
Disruption of local microbial irritation and host immune response can result in inflammation and tissue destruction in periodontitis. Studies on the modulation of macrophage polarization could help attenuate immune responses in periodontal tissues. To investigate the effect of ubiquitin-specific protease-7 (USP7) and its inhibitor P5091 on the polarization of macrophages in periodontitis, gene expression in periodontitis tissues and normal control were analyzed via single-cell RNA sequencing data and mice model experimental periodontitis. RAW264.7 cells were induced to M1 polarization with LPS + IFN-γ and M2 polarization with IL-4. USP7 was knocked down using lentivirus, and the effect of USP7 inhibitor P5091 on macrophage polarization was comparatively analyzed. The expression of Usp7 and polarization markers were detected by qRT-PCR. Western blot was used to examine the polarization markers and pathway-associated proteins. Results indicated that USP7 expression was elevated in tissues affected by periodontitis. Periodontitis macrophages and M1 polarized macrophages had higher USP7 expression. Knockdown of USP7 revealed an inhibition of both M1 and M2 macrophage polarization. Inhibition of USP7 with P5091 resulted in the decreased expression of M1 polarization markers and phosphorylation of P65, but the increased expression of M2 polarization markers and phosphorylation of STAT6. In conclusion, USP7 is involved in regulating macrophage polarization in periodontitis and its inhibitor P5091 may contribute to the prevention of periodontitis.
{"title":"USP7 - A novel target for controlling periodontal inflammation through modulation of macrophage polarization","authors":"Yan Wang , Hailin Mu , Baochen Yang , Chang Yang, Wei Dong, Jiawei Wang","doi":"10.1016/j.imlet.2025.106981","DOIUrl":"10.1016/j.imlet.2025.106981","url":null,"abstract":"<div><div>Disruption of local microbial irritation and host immune response can result in inflammation and tissue destruction in periodontitis. Studies on the modulation of macrophage polarization could help attenuate immune responses in periodontal tissues. To investigate the effect of ubiquitin-specific protease-7 (USP7) and its inhibitor P5091 on the polarization of macrophages in periodontitis, gene expression in periodontitis tissues and normal control were analyzed via single-cell RNA sequencing data and mice model experimental periodontitis. RAW264.7 cells were induced to M1 polarization with LPS + IFN-γ and M2 polarization with IL-4. USP7 was knocked down using lentivirus, and the effect of USP7 inhibitor P5091 on macrophage polarization was comparatively analyzed. The expression of Usp7 and polarization markers were detected by qRT-PCR. Western blot was used to examine the polarization markers and pathway-associated proteins. Results indicated that USP7 expression was elevated in tissues affected by periodontitis. Periodontitis macrophages and M1 polarized macrophages had higher USP7 expression. Knockdown of USP7 revealed an inhibition of both M1 and M2 macrophage polarization. Inhibition of USP7 with P5091 resulted in the decreased expression of M1 polarization markers and phosphorylation of P65, but the increased expression of M2 polarization markers and phosphorylation of STAT6. In conclusion, USP7 is involved in regulating macrophage polarization in periodontitis and its inhibitor P5091 may contribute to the prevention of periodontitis.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106981"},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395809","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}
Myasthenia gravis (MG) is an autoimmune disease characterized by disrupted neuromuscular synaptic transmission. Efgartigimod, a human Fc receptor antagonist, has been approved for patients with MG. Its potential use for other IgG-mediated neurological autoimmune diseases is unclear. This study aimed to retrospectively evaluate the efficacy and safety of efgartigimod in patients with neurological autoimmune diseases.
Methods
This retrospective study investigated patients with neurological autoimmune diseases who were treated with efgartigimod in the Henan Provincial People's Hospital. The efficacy of the medication was analyzed using the quality-of-life improvement score and the IgG level pre- and post-efgartigimod treatment. The safety of the medication was assessed by considering adverse events and blood parameters. The blood parameters, including routine blood parameters, coagulation, liver, kidney, and immune function.
Results
Seventeen patients received efgartigimod in the Henan Provincial People's Hospital from September 1, 2023, to January 31, 2024. In MG patients, myasthenia gravis activities of daily living (MG-ADL) reduced after efgartigimod treatment for 4 weeks compared with baseline (P < 0.05). Autoimmune encephalitis (AE) is a group of inflammatory disease with antibodies against neuronal synaptic and cell surface antigens. Similarly, patients with AE had a statistically significant reduction in modified Rankin scale (mRS) after efgartigimod treatment for 4 weeks compared with baseline (P < 0.05). Guillain Barre syndrome (GBS) is an immune-mediated disease of the peripheral nerves and nerve roots. However, the inflammatory neuropathy cause and treatment (INCAT) scale score didn't statistically differ in GBS patients before and after efgartigimod treatment (P > 0.05). The IgG levels significantly reduced after the first infusion and gradually decreased after multiple infusions (P < 0.05). Most subjects did not have increased IgG serum levels before treatment. IgA, IgM, and complement levels didn't differ significantly with efgartigimod treatment (P > 0.05). There were no changes in blood parameters during the treatment (P > 0.05).
Conclusions
Efgartigimod was effective and safe in neurological IgG-mediated autoimmune diseases, even in patients without increased IgG serum levels.
{"title":"Efficacy and safety of efgartigimod in patients with neurological autoimmune diseases","authors":"Jin Qin , Wei Li, Lipin Yuan, Huiqin Liu, Rui Pang, Jiewen Zhang","doi":"10.1016/j.imlet.2025.106983","DOIUrl":"10.1016/j.imlet.2025.106983","url":null,"abstract":"<div><h3>Objective</h3><div>Myasthenia gravis (MG) is an autoimmune disease characterized by disrupted neuromuscular synaptic transmission. Efgartigimod, a human Fc receptor antagonist, has been approved for patients with MG. Its potential use for other IgG-mediated neurological autoimmune diseases is unclear. This study aimed to retrospectively evaluate the efficacy and safety of efgartigimod in patients with neurological autoimmune diseases.</div></div><div><h3>Methods</h3><div>This retrospective study investigated patients with neurological autoimmune diseases who were treated with efgartigimod in the Henan Provincial People's Hospital. The efficacy of the medication was analyzed using the quality-of-life improvement score and the IgG level pre- and post-efgartigimod treatment. The safety of the medication was assessed by considering adverse events and blood parameters. The blood parameters, including routine blood parameters, coagulation, liver, kidney, and immune function.</div></div><div><h3>Results</h3><div>Seventeen patients received efgartigimod in the Henan Provincial People's Hospital from September 1, 2023, to January 31, 2024. In MG patients, myasthenia gravis activities of daily living (MG-ADL) reduced after efgartigimod treatment for 4 weeks compared with baseline (<em>P</em> < 0.05). Autoimmune encephalitis (AE) is a group of inflammatory disease with antibodies against neuronal synaptic and cell surface antigens. Similarly, patients with AE had a statistically significant reduction in modified Rankin scale (mRS) after efgartigimod treatment for 4 weeks compared with baseline (<em>P</em> < 0.05). Guillain Barre syndrome (GBS) is an immune-mediated disease of the peripheral nerves and nerve roots. However, the inflammatory neuropathy cause and treatment (INCAT) scale score didn't statistically differ in GBS patients before and after efgartigimod treatment (<em>P</em> > 0.05). The IgG levels significantly reduced after the first infusion and gradually decreased after multiple infusions (<em>P</em> < 0.05). Most subjects did not have increased IgG serum levels before treatment. IgA, IgM, and complement levels didn't differ significantly with efgartigimod treatment (<em>P</em> > 0.05). There were no changes in blood parameters during the treatment (<em>P</em> > 0.05).</div></div><div><h3>Conclusions</h3><div>Efgartigimod was effective and safe in neurological IgG-mediated autoimmune diseases, even in patients without increased IgG serum levels.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106983"},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407017","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 : 2025-02-09DOI: 10.1016/j.imlet.2025.106979
Lizandra Moura Paravidine Sasaki, Maria Eduarda Canellas-de-Castro, Geraldo Magela Fernandes, Felipe Motta, David Alves de Araújo, Heidi Luise Schulte, Gabriela Profírio Jardim-Santos, Ângelo Pereira da Silva, Aleida Oliveira de Carvalho, Yacara Ribeiro Pereira, Clara Correia de Siracusa, Isadora Pastrana Rabelo, Agenor de Castro Moreirados Santos, Caroline de Oliveira Alves, Lucas Lauand, Rodrigo de Resende Nery, Dayde Lane Mendonça-Silva, Rosana Tristão, José Alfredo Lacerda de Jesus, Karina Nascimento Costa, Luiz Cláudio Gonçalves de Castro, Patricia Shu Kurizky, Otávio de Toledo Nóbrega, Laila Salmen Espindola, Jordana Grazziela Alves Coelho-Dos-Reis, Joaquim Pedro Brito-de-Sousa, Ismael Artur Costa-Rocha, Ana Carolina Campi-Azevedo, Vanessa Peruhype-Magalhães, Andrea Teixeira-Carvalho, Ciro Martins Gomes, Cleandro Pires de Albuquerque, Alexandre Anderson de Sousa Munhoz Soares, Alberto Moreno Zaconeta, Olindo Assis Martins-Filho, Licia Maria Henrique da Mota
The present study intended to characterize the profile of soluble immune mediators in serum samples and in the cerebrospinal fluid (CSF) microenvironment from parturients with acute and convalescent COVID-19 as compared to healthy controls (HC), during the circulation of B.1.1.28 and B.1.1.33 SARS-CoV-2 strains which were identified during the initial spread of COVID-19 in Brazil. Data demonstrated increased levels of immune mediators in serum at acute infection with a clear waning during convalescent COVID-19. Conversely, a progressive increase of immune mediators was observed in CSF from acute infection towards convalescent COVID-19. Immune mediator signatures and integrative correlation circuits further confirmed these findings and supported the existence of dichotomic microenvironments in serum and CSF compartments. While a waning of correlations involving pro-inflammatory cytokines with increased connectivity of regulatory cytokines were observed in serum samples from acute towards convalescent COVID-19, an increasing frequency of correlations mediated by pro-inflammatory cytokines with decreased connectivity of regulatory cytokine were the hallmark of CSF. Correlations analysis identified a set of molecules associated with the dichotomic crosstalk between serum and CSF compartments, including chemokines (CXCL8, CCL5, CXCL10) and regulatory cytokines (IL-4 and IL-9). These immune biomarkers may represent potential targets for therapeutic strategies in parturients with COVID-19. Together, these findings demonstrated the existence of a divergent landscape of soluble immune mediators in serum and CSF, emphasizing the relevance of understanding the systemic and compartmentalized immune response elicited by SARS-CoV-2 infection during pregnancy.
{"title":"Systemic and cerebrospinal fluid immune mediators coordinate a dichotomic microenvironment in parturients with acute or convalescent phases of COVID-19.","authors":"Lizandra Moura Paravidine Sasaki, Maria Eduarda Canellas-de-Castro, Geraldo Magela Fernandes, Felipe Motta, David Alves de Araújo, Heidi Luise Schulte, Gabriela Profírio Jardim-Santos, Ângelo Pereira da Silva, Aleida Oliveira de Carvalho, Yacara Ribeiro Pereira, Clara Correia de Siracusa, Isadora Pastrana Rabelo, Agenor de Castro Moreirados Santos, Caroline de Oliveira Alves, Lucas Lauand, Rodrigo de Resende Nery, Dayde Lane Mendonça-Silva, Rosana Tristão, José Alfredo Lacerda de Jesus, Karina Nascimento Costa, Luiz Cláudio Gonçalves de Castro, Patricia Shu Kurizky, Otávio de Toledo Nóbrega, Laila Salmen Espindola, Jordana Grazziela Alves Coelho-Dos-Reis, Joaquim Pedro Brito-de-Sousa, Ismael Artur Costa-Rocha, Ana Carolina Campi-Azevedo, Vanessa Peruhype-Magalhães, Andrea Teixeira-Carvalho, Ciro Martins Gomes, Cleandro Pires de Albuquerque, Alexandre Anderson de Sousa Munhoz Soares, Alberto Moreno Zaconeta, Olindo Assis Martins-Filho, Licia Maria Henrique da Mota","doi":"10.1016/j.imlet.2025.106979","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.106979","url":null,"abstract":"<p><p>The present study intended to characterize the profile of soluble immune mediators in serum samples and in the cerebrospinal fluid (CSF) microenvironment from parturients with acute and convalescent COVID-19 as compared to healthy controls (HC), during the circulation of B.1.1.28 and B.1.1.33 SARS-CoV-2 strains which were identified during the initial spread of COVID-19 in Brazil. Data demonstrated increased levels of immune mediators in serum at acute infection with a clear waning during convalescent COVID-19. Conversely, a progressive increase of immune mediators was observed in CSF from acute infection towards convalescent COVID-19. Immune mediator signatures and integrative correlation circuits further confirmed these findings and supported the existence of dichotomic microenvironments in serum and CSF compartments. While a waning of correlations involving pro-inflammatory cytokines with increased connectivity of regulatory cytokines were observed in serum samples from acute towards convalescent COVID-19, an increasing frequency of correlations mediated by pro-inflammatory cytokines with decreased connectivity of regulatory cytokine were the hallmark of CSF. Correlations analysis identified a set of molecules associated with the dichotomic crosstalk between serum and CSF compartments, including chemokines (CXCL8, CCL5, CXCL10) and regulatory cytokines (IL-4 and IL-9). These immune biomarkers may represent potential targets for therapeutic strategies in parturients with COVID-19. Together, these findings demonstrated the existence of a divergent landscape of soluble immune mediators in serum and CSF, emphasizing the relevance of understanding the systemic and compartmentalized immune response elicited by SARS-CoV-2 infection during pregnancy.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"106979"},"PeriodicalIF":3.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399152","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 : 2025-02-07DOI: 10.1016/j.imlet.2025.106980
Marcus James Robinson, David Mathew Tarlinton
Antibodies of the IgE and IgG1 isotypes are relevant for type 2 immunity. In vivo, the production of both is elevated by IL-4, but differentially affected by IL-21, with IgE suppressed and IgG1 production enhanced by IL-21. However, whether the cytokines drive these outcomes primarily by impacting antibody-secreting, proliferating plasmablasts (PB), or their germinal center B cell precursors, is challenging to unravel. In vitro analyses using Nojima cultures, wherein naïve B cells are activated on fibroblasts co-expressing CD40L and BAFF, allows for evaluation of this problem. Here, we explore how IL-4 and IL-21 alone and in combination affect Nojima-cultured B cell proliferation and fate, asking what is unique or redundant about exposure to each. In secondary culture, as expected, IL-21 amplified replicative expansion. IL-21 also selectively promoted the differentiation of IgG1+ B cells into PB. The effect was countermanded by synchronous exposure to IL-4, suggesting competing signaling pathways are triggered by the two cytokines independently. Secondary culture with IL-4 alone promoted IgE+ B cell genesis without increasing replicative expansion. Combined exposure to IL-21 and IL-4 led to increased IgE class-switching and proliferative expansion, suggesting that once B cells are switched to IgE, IL-21 can promote IgE+ B cell proliferation. Thus, in culture IL-21 operates to promote proliferation and also drives differentiation of IgG1+ B cells into PB whereas IL-4 has an ongoing role in IgE B cell genesis. The balance of IL-4 and IL-21 thus impacts the fate of in vitro-generated germinal center B cells and highlights how the notable IgE-suppressing effects of IL-21 in vivo likely precede the class-switch step, after which IL-21 may amplify IgE production by virtue of its pro-proliferative effects.
{"title":"IL-21 promotes plasmablast differentiation independently of proliferation in vitro","authors":"Marcus James Robinson, David Mathew Tarlinton","doi":"10.1016/j.imlet.2025.106980","DOIUrl":"10.1016/j.imlet.2025.106980","url":null,"abstract":"<div><div>Antibodies of the IgE and IgG1 isotypes are relevant for type 2 immunity. <em>In vivo</em>, the production of both is elevated by IL-4, but differentially affected by IL-21, with IgE suppressed and IgG1 production enhanced by IL-21. However, whether the cytokines drive these outcomes primarily by impacting antibody-secreting, proliferating plasmablasts (PB), or their germinal center B cell precursors, is challenging to unravel. <em>In vitro</em> analyses using Nojima cultures, wherein naïve B cells are activated on fibroblasts co-expressing CD40L and BAFF, allows for evaluation of this problem. Here, we explore how IL-4 and IL-21 alone and in combination affect Nojima-cultured B cell proliferation and fate, asking what is unique or redundant about exposure to each. In secondary culture, as expected, IL-21 amplified replicative expansion. IL-21 also selectively promoted the differentiation of IgG1<sup>+</sup> B cells into PB. The effect was countermanded by synchronous exposure to IL-4, suggesting competing signaling pathways are triggered by the two cytokines independently. Secondary culture with IL-4 alone promoted IgE<sup>+</sup> B cell genesis without increasing replicative expansion. Combined exposure to IL-21 and IL-4 led to increased IgE class-switching and proliferative expansion, suggesting that once B cells are switched to IgE, IL-21 can promote IgE+ B cell proliferation. Thus, in culture IL-21 operates to promote proliferation and also drives differentiation of IgG1+ B cells into PB whereas IL-4 has an ongoing role in IgE B cell genesis. The balance of IL-4 and IL-21 thus impacts the fate of <em>in vitro-</em>generated germinal center B cells and highlights how the notable IgE-suppressing effects of IL-21 <em>in vivo</em> likely precede the class-switch step, after which IL-21 may amplify IgE production by virtue of its pro-proliferative effects.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106980"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strains is an interesting topic of research where maternal immunoglobulins appear to be important. This proof-of-concept study explored the binding pattern of IgA1, IgA2, IgM, and IgG classes to a commensal bacterial in human colostrum and the stool of breastfed neonates. We used flow cytometry coupled with 16S rRNA gene sequencing in human colostrum and neonatal feces samples to characterize this Ig-microbiota association. We observed that in human colostrum samples, IgA2 and IgM bind alfa and beta Proteobacteria, which can potentially stimulate neonatal immune system development in the gut. Other immunoglobulins like IgG predominantly bind facultative anaerobes belonging to the Firmicutes phylum, reported as part of human milk microbiota and pioneer colonizers of the neonatal gut. Maternal immunoglobulins also bind a wide diversity of bacteria in the neonatal stool. For instance, IgA2 and IgM bound more members of the phylum Bacteroidetes in comparison to IgG, these Bacteroidetes and some firmicutes have been reported as late colonizers of the neonatal gut, and their presence is important due to their ability to produce important short chain fatty acids like propionate and butyrate. Our results support the current view that microbial and immunoglobulin transference is crucial for developing the neonate's immune system and individual gut microbiota.
{"title":"Maternal immunoglobulins differentially bind a diverse bacterial community in human colostrum and the stool of breastfed neonates","authors":"Karina Corona-Cervantes , Erick Sánchez-Salguero , Paola Berenice Zárate-Segura , Aparna Krishnakumar , Alberto Piña-Escobedo , Martín Noé Rangel-Calvillo , Tito Ramírez-Lozada , Gustavo Acosta-Altamirano , Noemí del Socorro Lázaro-Pérez , Mónica Sierra-Martínez , Leopoldo Santos-Argumedo , Jaime García-Mena","doi":"10.1016/j.imlet.2025.106978","DOIUrl":"10.1016/j.imlet.2025.106978","url":null,"abstract":"<div><div>In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strains is an interesting topic of research where maternal immunoglobulins appear to be important. This proof-of-concept study explored the binding pattern of IgA1, IgA2, IgM, and IgG classes to a commensal bacterial in human colostrum and the stool of breastfed neonates. We used flow cytometry coupled with 16S rRNA gene sequencing in human colostrum and neonatal feces samples to characterize this Ig-microbiota association. We observed that in human colostrum samples, IgA2 and IgM bind alfa and beta Proteobacteria, which can potentially stimulate neonatal immune system development in the gut. Other immunoglobulins like IgG predominantly bind facultative anaerobes belonging to the Firmicutes phylum, reported as part of human milk microbiota and pioneer colonizers of the neonatal gut. Maternal immunoglobulins also bind a wide diversity of bacteria in the neonatal stool. For instance, IgA2 and IgM bound more members of the phylum Bacteroidetes in comparison to IgG, these Bacteroidetes and some firmicutes have been reported as late colonizers of the neonatal gut, and their presence is important due to their ability to produce important short chain fatty acids like propionate and butyrate. Our results support the current view that microbial and immunoglobulin transference is crucial for developing the neonate's immune system and individual gut microbiota.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"273 ","pages":"Article 106978"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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