Pub Date : 2024-06-22DOI: 10.1016/j.clim.2024.110297
Xiaoyan Zhang , Xuan Zhang , Xin Huang , Javeed Iqbal , Timothy W. McKeithan , Wing C. Chan , Julie M. Vose , Chengfeng Bi , Xiaofan Zhu , Kai Fu
Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17∼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17∼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17∼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17∼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17∼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17∼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.
{"title":"MiR-17∼92 is involved in NF-κB activation via targeting the ubiquitin-editing proteins to mediate RIP1 complex polyubiquitinations in ABC-DLBCL","authors":"Xiaoyan Zhang , Xuan Zhang , Xin Huang , Javeed Iqbal , Timothy W. McKeithan , Wing C. Chan , Julie M. Vose , Chengfeng Bi , Xiaofan Zhu , Kai Fu","doi":"10.1016/j.clim.2024.110297","DOIUrl":"10.1016/j.clim.2024.110297","url":null,"abstract":"<div><p>Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17∼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17∼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17∼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17∼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17∼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17∼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442208","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 : 2024-06-22DOI: 10.1016/j.clim.2024.110296
Panyu Yang , Xi Tang , Penghao Li , Zhongyu Liu , Chao Zhang , Yuxiang Wu , Xiaoxi Zeng , Yongkang Wu
Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895–0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796–0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.
{"title":"A nomogram to predict the risk of proliferative lupus nephritis in patients with systemic lupus erythematosus involving the kidneys","authors":"Panyu Yang , Xi Tang , Penghao Li , Zhongyu Liu , Chao Zhang , Yuxiang Wu , Xiaoxi Zeng , Yongkang Wu","doi":"10.1016/j.clim.2024.110296","DOIUrl":"10.1016/j.clim.2024.110296","url":null,"abstract":"<div><p>Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895–0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796–0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445775","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 : 2024-06-22DOI: 10.1016/j.clim.2024.110292
Andrés Caballero-Oteyza , Laura Crisponi , Xiao P. Peng , Hongying Wang , Pavla Mrovecova , Stefania Olla , Chiara Siguri , Farida Marnissi , Zineb Jouhadi , Ivona Aksentijevich , Bodo Grimbacher , Michele Proietti
OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative (DN) effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype and provide experimental evidence for its pathogenicity. We go on to systematically review the literature for OTULIN-associated conditions by using the GenIA database (www.geniadb.net) to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and inform future variant evaluation, as well as the development of diagnostic and management guidelines. It also identifies current knowledge gaps and raises additional questions warranting future investigation.
{"title":"OTULIN-related conditions: Report of a new case and review of the literature using GenIA","authors":"Andrés Caballero-Oteyza , Laura Crisponi , Xiao P. Peng , Hongying Wang , Pavla Mrovecova , Stefania Olla , Chiara Siguri , Farida Marnissi , Zineb Jouhadi , Ivona Aksentijevich , Bodo Grimbacher , Michele Proietti","doi":"10.1016/j.clim.2024.110292","DOIUrl":"10.1016/j.clim.2024.110292","url":null,"abstract":"<div><p><em>OTULIN</em> encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in <em>OTULIN</em> cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic <em>OTULIN</em> LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative (DN) effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype and provide experimental evidence for its pathogenicity. We go on to systematically review the literature for OTULIN-associated conditions by using the GenIA database (<span>www.geniadb.net</span><svg><path></path></svg>) to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the <em>OTULIN</em> pathogenic variants may lead to human immune disease. This review may help variant classification activities and inform future variant evaluation, as well as the development of diagnostic and management guidelines. It also identifies current knowledge gaps and raises additional questions warranting future investigation.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004017/pdfft?md5=71e775496cfaf7fb5c3f9535db00b4ed&pid=1-s2.0-S1521661624004017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-22DOI: 10.1016/j.clim.2024.110298
Minjie Luo , Nina He , Qing Xu , Zhongchi Wen , Ziqin Wang , Jie Zhao , Ying Liu
Prostaglandins (PGs) play a crucial and multifaceted role in various physiological processes such as intercellular signaling, inflammation regulation, neurotransmission, vasodilation, vasoconstriction, and reproductive functions. The diversity and biological significance of these effects are contingent upon the specific types or subtypes of PGs, with each PG playing a crucial role in distinct physiological and pathological processes. Particularly within the immune system, PGs are essential in modulating the function of immune cells and the magnitude and orientation of immune responses. Hence, a comprehensive comprehension of the functions PG signaling pathways in immunosuppressive regulation holds substantial clinical relevance for disease prevention and treatment strategies. The manuscript provides a review of recent developments in PG signaling in immunosuppressive regulation. Furthermore, the potential clinical applications of PGs in immunosuppression are also discussed. While research into the immunosuppressive effects of PGs required further exploration, targeted therapies against their immunosuppressive pathways might open new avenues for disease prevention and treatment.
{"title":"Roles of prostaglandins in immunosuppression","authors":"Minjie Luo , Nina He , Qing Xu , Zhongchi Wen , Ziqin Wang , Jie Zhao , Ying Liu","doi":"10.1016/j.clim.2024.110298","DOIUrl":"10.1016/j.clim.2024.110298","url":null,"abstract":"<div><p>Prostaglandins (PGs) play a crucial and multifaceted role in various physiological processes such as intercellular signaling, inflammation regulation, neurotransmission, vasodilation, vasoconstriction, and reproductive functions. The diversity and biological significance of these effects are contingent upon the specific types or subtypes of PGs, with each PG playing a crucial role in distinct physiological and pathological processes. Particularly within the immune system, PGs are essential in modulating the function of immune cells and the magnitude and orientation of immune responses. Hence, a comprehensive comprehension of the functions PG signaling pathways in immunosuppressive regulation holds substantial clinical relevance for disease prevention and treatment strategies. The manuscript provides a review of recent developments in PG signaling in immunosuppressive regulation. Furthermore, the potential clinical applications of PGs in immunosuppression are also discussed. While research into the immunosuppressive effects of PGs required further exploration, targeted therapies against their immunosuppressive pathways might open new avenues for disease prevention and treatment.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442209","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 : 2024-06-22DOI: 10.1016/j.clim.2024.110294
Ashley Sang Eun Lee , Roshini S. Abraham , Amrita Basu , Howard Lederman , Charlotte Cunningham-Rundles
{"title":"ATAXIA-telangiectasia with compound heterozygous ATM mutations discovered on abnormal newborn screen","authors":"Ashley Sang Eun Lee , Roshini S. Abraham , Amrita Basu , Howard Lederman , Charlotte Cunningham-Rundles","doi":"10.1016/j.clim.2024.110294","DOIUrl":"10.1016/j.clim.2024.110294","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445776","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 : 2024-06-21DOI: 10.1016/j.clim.2024.110287
Aman Damara , Joanna Wegner , Emily R. Trzeciak , Antonia Kolb , Mahsa Nastaranpour , Rahul Khatri , Andrea Tuettenberg , Daniela Kramer , Stephan Grabbe , Fatemeh Shahneh
LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected naïve CD4+ T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics.
LL37 单独或与自身 DNA 复合物会引发髓系细胞的炎症反应,并在银屑病和系统性红斑狼疮等系统性自身免疫性疾病的发病过程中发挥关键作用。我们证实,LL37/自DNA复合物能诱导单核细胞发生长期代谢和表观遗传变化,从而增强它们对后续刺激的反应能力。用 LL37/self-DNA复合物训练的单核细胞和来自银屑病患者的单核细胞表现出更高的糖酵解和氧化磷酸化率,促炎细胞因子释放增加,并影响了幼稚CD4+ T细胞。此外,KDM6A/B(组蛋白 3 上赖氨酸 27 的去甲基化酶)在银屑病单核细胞和经 LL37/自身 DNA 复合物处理的单核细胞中上调。抑制 KDM6A/B 可减少 LL37/自身 DNA 处理单核细胞产生的促炎细胞因子、代谢活性和诱导产生 IL-17 的 T 细胞,从而逆转训练有素的免疫表型。我们的研究结果强调了 LL37/self-DNA诱导的先天免疫记忆在银屑病发病机制中的作用,揭示了它对单核细胞和 T 细胞动态的影响。
{"title":"LL37/self-DNA complexes mediate monocyte reprogramming","authors":"Aman Damara , Joanna Wegner , Emily R. Trzeciak , Antonia Kolb , Mahsa Nastaranpour , Rahul Khatri , Andrea Tuettenberg , Daniela Kramer , Stephan Grabbe , Fatemeh Shahneh","doi":"10.1016/j.clim.2024.110287","DOIUrl":"10.1016/j.clim.2024.110287","url":null,"abstract":"<div><p>LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected naïve CD4<sup>+</sup> T cells. Additionally, KDM6A/B, a demethylase of lysine 27 on histone 3, was upregulated in psoriatic monocytes and monocytes treated with LL37/self-DNA complexes. Inhibition of KDM6A/B reversed the trained immune phenotype by reducing proinflammatory cytokine production, metabolic activity, and the induction of IL-17-producing T cells by LL37/self-DNA-treated monocytes. Our findings highlight the role of LL37/self-DNA-induced innate immune memory in psoriasis pathogenesis, uncovering its impact on monocyte and T cell dynamics.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003966/pdfft?md5=b66157a1bc7693c17a0092840843e743&pid=1-s2.0-S1521661624003966-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20DOI: 10.1016/j.clim.2024.110291
Tianyu Wang , Lichen Li , Shan Cao , Lele Sun , Gongqi Yu , Qianqian Xia , Tingting Liu , Qing Zhao , Zhenzhen Wang , Chuan Wang , Baoqi Yang , Yongxia Liu , Xuechao Chen , Shengli Chen , Guizhi Zhou , Hong Liu , Yonghu Sun , Furen Zhang
Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LABD, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.
线性 IgA 大疱性皮肤病(LABD)和疱疹性皮炎(DH)是 IgA 介导的自身免疫性大疱性皮肤病的主要亚型。我们试图通过血清蛋白质组学来了解疾病的病因。我们利用 Olink 高通量蛋白质组学评估了 LAB、DH 和健康对照组的 92 个器官损伤生物标志物。阳性血清蛋白质组学生物标志物与临床特征和 HLA 类型相关。对 IgA 沉积型牛皮癣与对照组进行的靶向蛋白质组学分析表明,生物标志物有所升高。进一步的聚类和富集分析确定了LABD和DH之间不同的聚类,突出了烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的参与。比较分析发现了区分 LABD 和 DH 的生物标记物,并在皮肤病变中得到了验证。最后,与 DEPs 的定性相关分析表明,六个生物标记物(NBN、NCF2、CAPG、FES、BID 和 PXN)对 DH 患者的预后有较好的影响。这些发现为区分 IgA 沉积性大疱病的疾病亚型提供了潜在的生物标志物。
{"title":"Targeted serum proteome profiling reveals nicotinamide adenine dinucleotide phosphate (NADPH)-related biomarkers to discriminate linear IgA bullous disorder from dermatitis herpetiformis","authors":"Tianyu Wang , Lichen Li , Shan Cao , Lele Sun , Gongqi Yu , Qianqian Xia , Tingting Liu , Qing Zhao , Zhenzhen Wang , Chuan Wang , Baoqi Yang , Yongxia Liu , Xuechao Chen , Shengli Chen , Guizhi Zhou , Hong Liu , Yonghu Sun , Furen Zhang","doi":"10.1016/j.clim.2024.110291","DOIUrl":"10.1016/j.clim.2024.110291","url":null,"abstract":"<div><p>Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LABD, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004005/pdfft?md5=72b7da4f3da32420f326b1adf790dfef&pid=1-s2.0-S1521661624004005-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20DOI: 10.1016/j.clim.2024.110289
Hyun Lee , Miseon Lee , Chae Lyul Lim , Hye Seon Park , In Hye Song , Byung-Kwan Jeong , Dong Kwan Kim , Yong-Hee Kim , Sehoon Choi , Geun Dong Lee , Sae Byul Lee , SungWook Jung , Gyungyub Gong , Sung-Bae Kim , Changhoon Yoo , Joo Young Kim , Hee Jin Lee
Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4+/CD8+ ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.
{"title":"Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets","authors":"Hyun Lee , Miseon Lee , Chae Lyul Lim , Hye Seon Park , In Hye Song , Byung-Kwan Jeong , Dong Kwan Kim , Yong-Hee Kim , Sehoon Choi , Geun Dong Lee , Sae Byul Lee , SungWook Jung , Gyungyub Gong , Sung-Bae Kim , Changhoon Yoo , Joo Young Kim , Hee Jin Lee","doi":"10.1016/j.clim.2024.110289","DOIUrl":"10.1016/j.clim.2024.110289","url":null,"abstract":"<div><p>Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and <em>in vivo</em> efficacy tests. TIL expansion was observed in all cases, regardless of <em>EGFR</em> mutation status. There was also an increase in the median CD4<sup>+</sup>/CD8<sup>+</sup> ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with <em>EGFR</em> mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had <em>EGFR</em> mutations. <em>In vivo</em> functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440264","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 : 2024-06-20DOI: 10.1016/j.clim.2024.110286
{"title":"The ‘T' (Tsokos) cells: Celebrating Dr. George Tsokos' pioneering contributions to clinical immunology","authors":"","doi":"10.1016/j.clim.2024.110286","DOIUrl":"10.1016/j.clim.2024.110286","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440266","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 : 2024-06-15DOI: 10.1016/j.clim.2024.110281
Coziana Ciurtin , Ghada Adly Helmy , Alexia Correia Ferreira , Jessica J. Manson , Elizabeth C. Jury , Thomas McDonnell
C-reactive protein (CRP) is an inflammatory biomarker with associated clinical utility in a wide number of inflammatory disorders, including rheumatoid arthritis (RA). The interaction of CRP with pro-inflammatory cytokines has been explored before, however its role in complement regulation is more subtle, where CRP is capable of both up and downregulating the complement cascade. CRP is produced in a pentameric form and can dissociate to a monomeric form in circulation which has significant implications for its ability to interact with receptors and binding partners. This dichotomy of CRP structure could have relevance in patients with RA who have significant dysfunction in their complement cascade and also widely varying CRP levels including at the time of flare. This review aims to bring together current knowledge of CRP in its various forms, its effects on complement function and how this could influence pathology in the context of RA.
{"title":"A tale of two functions: C-reactive protein complement-ary structures and their role in rheumatoid arthritis","authors":"Coziana Ciurtin , Ghada Adly Helmy , Alexia Correia Ferreira , Jessica J. Manson , Elizabeth C. Jury , Thomas McDonnell","doi":"10.1016/j.clim.2024.110281","DOIUrl":"10.1016/j.clim.2024.110281","url":null,"abstract":"<div><p>C-reactive protein (CRP) is an inflammatory biomarker with associated clinical utility in a wide number of inflammatory disorders, including rheumatoid arthritis (RA). The interaction of CRP with pro-inflammatory cytokines has been explored before, however its role in complement regulation is more subtle, where CRP is capable of both up and downregulating the complement cascade. CRP is produced in a pentameric form and can dissociate to a monomeric form in circulation which has significant implications for its ability to interact with receptors and binding partners. This dichotomy of CRP structure could have relevance in patients with RA who have significant dysfunction in their complement cascade and also widely varying CRP levels including at the time of flare. This review aims to bring together current knowledge of CRP in its various forms, its effects on complement function and how this could influence pathology in the context of RA.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003905/pdfft?md5=397fe8084f3264b5b0b1b47588435ea0&pid=1-s2.0-S1521661624003905-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141398017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}