Clinical immunology最新文献

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Pediatric lymphoproliferative disorders associated with inborn errors of immunity 与先天性免疫错误有关的小儿淋巴细胞增生性疾病。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-26 DOI: 10.1016/j.clim.2024.110332
Jinjun Cheng , Blachy J. Dávila Saldaña , Shanmuganathan Chandrakasan , Michael Keller
{"title":"Pediatric lymphoproliferative disorders associated with inborn errors of immunity","authors":"Jinjun Cheng ,&nbsp;Blachy J. Dávila Saldaña ,&nbsp;Shanmuganathan Chandrakasan ,&nbsp;Michael Keller","doi":"10.1016/j.clim.2024.110332","DOIUrl":"10.1016/j.clim.2024.110332","url":null,"abstract":"<div><p>Both non-malignant and malignant lymphoproliferative disorders (LPD) are commonly seen in patients with inborn errors of immunity (IEI), which may be the presenting manifestations or may develop during the IEI disease course. Here we review the clinical, histopathological, and molecular features of benign and malignant LPD associated with IEI and recognize the diagnostic challenges.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110332"},"PeriodicalIF":4.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787405","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}
引用次数: 0
IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs in clinically healed lesions are potential cellular candidates for recurrence of psoriasis 临床痊愈皮损中的 IL-17A/F 双倍产生 T 细胞、不稳定 Treg 和静止 TRM 是银屑病复发的潜在候选细胞
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-25 DOI: 10.1016/j.clim.2024.110328
Lu Peng , Wenqi Liu , Yufan Cheng , Ling Chen , Zhu Shen
{"title":"IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs in clinically healed lesions are potential cellular candidates for recurrence of psoriasis","authors":"Lu Peng ,&nbsp;Wenqi Liu ,&nbsp;Yufan Cheng ,&nbsp;Ling Chen ,&nbsp;Zhu Shen","doi":"10.1016/j.clim.2024.110328","DOIUrl":"10.1016/j.clim.2024.110328","url":null,"abstract":"<div><p>Biological antibodies targeting key cytokines such as IL-17 and IL-23 have revolutionized psoriasis outcome. However, the recurrence remains an urgent challenge to be addressed. Currently, most of the descriptions of skin T-cell characteristics in psoriasis are derived from lesional and non-lesional skin, and their characteristics in resolved lesions (clinically healed lesions) remain vague. In order to further elucidate the cellular mechanism of recurrence, we performed single-cell sequencing and multiplexed immunohistochemical staining of T-cell subsets in autologous resolved lesion (RL), on-site recurrent psoriatic lesion (PL), and adjacent normal-appearing skin (NS) of psoriasis. By comparing with PL and NS tissues, we identified three potential cellular candidates for recurrence in clinically healed lesions: IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs. Our results provide research clues for elucidating the immunological recurrence mechanism of psoriasis, and further work is needed to deepen our findings.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110328"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141781130","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}
引用次数: 0
Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders 疫苗挑战反应在评估原发性抗体缺乏症(包括常见变异性免疫缺陷病)方面的临床应用局限性。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-25 DOI: 10.1016/j.clim.2024.110320
Rohan Ameratunga , Hilary Longhurst , Euphemia Leung , Richard Steele , Klaus Lehnert , See-Tarn Woon
{"title":"Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders","authors":"Rohan Ameratunga ,&nbsp;Hilary Longhurst ,&nbsp;Euphemia Leung ,&nbsp;Richard Steele ,&nbsp;Klaus Lehnert ,&nbsp;See-Tarn Woon","doi":"10.1016/j.clim.2024.110320","DOIUrl":"10.1016/j.clim.2024.110320","url":null,"abstract":"<div><p>Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment.</p><p>Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis.</p><p>Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and <em>H. influenzae</em> type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23).</p><p>This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110320"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723257","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}
引用次数: 0
CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth CD137 的表达和信号功能驱动γδ T 细胞效应器的多效性功能,从而抑制细胞内结核杆菌的生长。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-25 DOI: 10.1016/j.clim.2024.110331
Xuejiao Ji , Guixian Huang , Ying Peng , Juechu Wang , Xia Cai , Enzhuo Yang , Liying Zhu , Yuan Wu , Wei Sha , Feifei Wang , Ling Shen , Hongbo Shen
{"title":"CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth","authors":"Xuejiao Ji ,&nbsp;Guixian Huang ,&nbsp;Ying Peng ,&nbsp;Juechu Wang ,&nbsp;Xia Cai ,&nbsp;Enzhuo Yang ,&nbsp;Liying Zhu ,&nbsp;Yuan Wu ,&nbsp;Wei Sha ,&nbsp;Feifei Wang ,&nbsp;Ling Shen ,&nbsp;Hongbo Shen","doi":"10.1016/j.clim.2024.110331","DOIUrl":"10.1016/j.clim.2024.110331","url":null,"abstract":"<div><p>Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, <em>Mycobacteria tuberculosis</em> (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ). Consistently, Mtb antigen (Ag) HMBPP stimulation induced sustainable high-level CD137 expression in fresh and activated Vγ2Vδ2 T cells from uninfected subjects, but not TB patients. CD137<sup>+</sup>Vγ2Vδ2 T-cell subtype predominantly displayed central memory phenotype and mounted better proliferative responses than CD137<sup>−</sup>Vγ2Vδ2 T-cells. In response to HMBPP, CD137<sup>+</sup>Vγ2Vδ2 T-cell subtype rapidly differentiated into greater numbers of pleiotropic effector cells producing anti-Mtb cytokines compared to CD137<sup>−</sup>Vγ2Vδ2 T subtype, with the non-canonical NF-κB pathway involved. CD137 expression in Vγ2Vδ2 T cells appeared to signal anti-Mtb effector functions leading to intracellular Mtb growth inhibition in Mɸ, and active TB disrupted such CD137-driven anti-Mtb effector functions. CD137<sup>+</sup>Vγ2Vδ2 T-cells subtype exhibited an epigenetic-driven high-level expression of <em>GM-CSF</em> and <em>de novo</em> production of GM-CSF critical for Vγ2Vδ2 T-cell controlling of Mtb growth in Mϕ. Concurrently, exosomes produced by CD137<sup>+</sup>Vγ2Vδ2 T cells potently inhibited intracellular mycobacterial growth. Furthermore, adoptive transfer of human CD137<sup>+</sup>Vγ2Vδ2 T cells to Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, our data suggest that CD137 expression/signaling drives pleiotropic γδ T-cell effector functions that inhibit intracellular Mtb growth.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110331"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787404","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}
引用次数: 0
Age-dependent decrease of circulating T follicular helper cells correlates with disease severity in elderly patients with COVID-19 循环 T 滤泡辅助细胞的减少与 COVID-19 老年患者的疾病严重程度有关。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-25 DOI: 10.1016/j.clim.2024.110329
Yihan Wang , Qiu Wang , Furong He , Nan Qiao , Xuejun Li , Liqun Wei , Lingjin Sun , Weiqian Dai , Ying Li , Xueyang Pang , Jiayi Hu , Chuan Huang , Guangchen Yang , Chongjie Pang , Zhidong Hu , Man Xing , Chunxiao Wan , Dongming Zhou
{"title":"Age-dependent decrease of circulating T follicular helper cells correlates with disease severity in elderly patients with COVID-19","authors":"Yihan Wang ,&nbsp;Qiu Wang ,&nbsp;Furong He ,&nbsp;Nan Qiao ,&nbsp;Xuejun Li ,&nbsp;Liqun Wei ,&nbsp;Lingjin Sun ,&nbsp;Weiqian Dai ,&nbsp;Ying Li ,&nbsp;Xueyang Pang ,&nbsp;Jiayi Hu ,&nbsp;Chuan Huang ,&nbsp;Guangchen Yang ,&nbsp;Chongjie Pang ,&nbsp;Zhidong Hu ,&nbsp;Man Xing ,&nbsp;Chunxiao Wan ,&nbsp;Dongming Zhou","doi":"10.1016/j.clim.2024.110329","DOIUrl":"10.1016/j.clim.2024.110329","url":null,"abstract":"<div><p>Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4<sup>+</sup> T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110329"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787403","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}
引用次数: 0
The effect of early life cytomegalovirus infection on the immune profile of children 早期巨细胞病毒感染对儿童免疫特征的影响。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-25 DOI: 10.1016/j.clim.2024.110330
Ilse Ekman , Anna-Mari Schroderus , Tytti Vuorinen , Mikael Knip , Riitta Veijola , Jorma Toppari , Jorma Ilonen , Johanna Lempainen , Tuure Kinnunen
{"title":"The effect of early life cytomegalovirus infection on the immune profile of children","authors":"Ilse Ekman ,&nbsp;Anna-Mari Schroderus ,&nbsp;Tytti Vuorinen ,&nbsp;Mikael Knip ,&nbsp;Riitta Veijola ,&nbsp;Jorma Toppari ,&nbsp;Jorma Ilonen ,&nbsp;Johanna Lempainen ,&nbsp;Tuure Kinnunen","doi":"10.1016/j.clim.2024.110330","DOIUrl":"10.1016/j.clim.2024.110330","url":null,"abstract":"<div><p>Cytomegalovirus (CMV) infection has a life-long impact on the immune system, particularly on memory T cells. However, the effect of early life CMV infection on the phenotype and functionality of T cells in infants and especially longitudinal changes occurring during childhood have not been explored in detail.</p><p>The phenotype and functionality of peripheral blood CD8+ and CD4+ T cells from children infected with CMV in early life (&lt; 6 months of age) was analyzed using high-dimensional flow cytometry. Samples from CMV IgG-seropositive (CMV+) children were collected at 6 months and 6 years of age and compared to samples from CMV-seronegative (CMV-) children.</p><p>Early life CMV infection caused multiple alterations within T cells. These include downregulation of CD28 expression and upregulation of CD57 expression within both CD27+ early and CD27- late effector memory CD8+ and CD4+ T-cells at 6 months of age. Of these changes, only alterations within the highly differentiated late effector memory compartment persisted at the age of 6 years.</p><p>Early life CMV-infection has a distinct impact on developing CD8+ and CD4+ memory T cell compartments. It appears to induce both temporary as well as longer-lasting alterations, which may affect the functionality of the immune system throughout life.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110330"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152166162400439X/pdfft?md5=931b03a110ce6e0633849a154751734a&pid=1-s2.0-S152166162400439X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787407","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}
引用次数: 0
T peripheral helper (Tph) cells, a marker of immune activation in cancer and autoimmune disorders T 周围辅助细胞(Tph)是癌症和自身免疫性疾病中免疫激活的标志。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-25 DOI: 10.1016/j.clim.2024.110325
Celia del Carmen Crespo Oliva , Marilyne Labrie , Hugues Allard-Chamard
{"title":"T peripheral helper (Tph) cells, a marker of immune activation in cancer and autoimmune disorders","authors":"Celia del Carmen Crespo Oliva ,&nbsp;Marilyne Labrie ,&nbsp;Hugues Allard-Chamard","doi":"10.1016/j.clim.2024.110325","DOIUrl":"10.1016/j.clim.2024.110325","url":null,"abstract":"<div><p>T peripheral helper (Tph) cells are a newly discovered subtype of CD4+ T cells that have emerged as the counterpart of T follicular helper (Tfh) cells in the peripheral tissues. These two cell types share some common characteristics, such as high levels of PD1 and CXCL13 expression, but differ in the expression of transcription factors and chemokine receptors. Tph cells have been studied in relation to B cells' effector functions, including cytokines production and antibody-mediated immune responses. However, their role in the inflammatory-mediated development of malignancies remains poorly understood. Tph cells were initially identified in the synovium of rheumatoid arthritis patients and have since been found to be expanded in several autoimmune diseases. They have been linked to a worse prognosis in autoimmune conditions, but intriguingly, their presence has been correlated with better outcomes in certain types of cancer. The functions of Tph cells are still being investigated, but recent data suggests their involvement in the assembly of tertiary lymphoid structures (TLS). Furthermore, their interaction with B cells, which have been mainly described as possessing a memory phenotype, promotes their development. In this review, we explore the role of Tph cells in peripheral immune responses during cancer and autoimmune disorders.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110325"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004340/pdfft?md5=9c1fe539a3be3c90c526f1d522650d25&pid=1-s2.0-S1521661624004340-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787406","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}
引用次数: 0
Novel hypermorphic variants in IRF2BP2 identified in patients with common variable immunodeficiency and autoimmunity 在常见变异性免疫缺陷和自身免疫患者中发现 IRF2BP2 的新型高形态变异。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-24 DOI: 10.1016/j.clim.2024.110326
Manfred Anim , Georgios Sogkas , Nadezhda Camacho-Ordonez , Gunnar Schmidt , Abdulwahab Elsayed , Michele Proietti , Torsten Witte , Bodo Grimbacher , Faranaz Atschekzei
{"title":"Novel hypermorphic variants in IRF2BP2 identified in patients with common variable immunodeficiency and autoimmunity","authors":"Manfred Anim ,&nbsp;Georgios Sogkas ,&nbsp;Nadezhda Camacho-Ordonez ,&nbsp;Gunnar Schmidt ,&nbsp;Abdulwahab Elsayed ,&nbsp;Michele Proietti ,&nbsp;Torsten Witte ,&nbsp;Bodo Grimbacher ,&nbsp;Faranaz Atschekzei","doi":"10.1016/j.clim.2024.110326","DOIUrl":"10.1016/j.clim.2024.110326","url":null,"abstract":"<div><p>The interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional regulator, functioning a transcriptional corepressor by interacting with the interferon regulatory factor-2. The ubiquitous expression of IRF2BP2 by diverse cell types and tissues suggests its potential involvement in different cell signalling pathways. <strong>Variants in</strong> <em>IRF2BP2</em> <strong>have been recently identified to cause familial common variable immunodeficiency (CVID) characterized by immune dysregulation.</strong></p><p>This study investigated three rare novel variants <strong>in</strong> <em>IRF2BP2</em><strong>,</strong> identified in patients with primary antibody deficiency and autoimmunity by whole exome-sequencing (WES). Following transient overexpression of EGFP-fused mutants in HEK293 cells and transfection in Jurkat cell lines, we used fluorescence microscopy, real-time PCR and Western blotting to analyze their effects on IRF2BP2 expression, subcellular localization, nuclear translocation of IRF2, and the transcriptional activation of NFκB1(p50).</p><p>We found altered IRF2BP2 mRNA and protein expression levels in the mutants compared to the wild type after IRF2BP2 overexpression. In confocal fluorescence microscopy, variants in the C-terminal RING finger domain showed an irregular aggregate formation and distribution instead of the expected nuclear localization compared to the variants in the N-terminal zinc finger domain and their wildtype counterpart. Immunoblotting revealed an impaired IRF2 and NFκB1 (p50) nuclear localization in the mutants compared to the IRF2BP2 wildtype counterpart. LPS stimulation reduced IRF2BP2 mRNA expression in the variants compared to the wild type.</p><p>Our findings significantly contribute to understanding the clinical significance of <em>IRF2BP2</em> mutations in the pathogenesis of immunodeficiency and immune dysregulation. We observed impairment of the nuclear translocation of IRF2 and NFκB1 (p50) due to the upregulation of IRF2BP2, potentially affecting specific gene expressions involved in immune regulation<em>.</em></p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110326"},"PeriodicalIF":4.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765691","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}
引用次数: 0
Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity 白细胞介素-1受体相关激酶-3的甲基化与多发性硬化症复发/活动的风险
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-23 DOI: 10.1016/j.clim.2024.110327
Mona M. Watany , Marwa M. Elhosary , Hemat E. El-Horany , Mahmoud E. El-Horany
{"title":"Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity","authors":"Mona M. Watany ,&nbsp;Marwa M. Elhosary ,&nbsp;Hemat E. El-Horany ,&nbsp;Mahmoud E. El-Horany","doi":"10.1016/j.clim.2024.110327","DOIUrl":"10.1016/j.clim.2024.110327","url":null,"abstract":"<div><p>This study retrospectively investigated the impact of interleukin-1 receptor-associated kinase-3 (IRAK-3/IRAK-M) silencing by methylation on the likelihood of multiple sclerosis (MS) activity. This cross-sectional study included 90 patients with MS: 45 with active disease (Group 1), 45 in remission (Group 2), and 45 healthy controls. The study included quantitation of IRAK-3 methylation index (MI%), IRAK-3 mRNA, and myeloid differentiation factor88 (MyD88) and assessment of NF-κB activity.</p><p>IRAK-3 MI% was significantly higher in group 1 compared to group 2, accompanied by lower IRAK-3 mRNA expression, elevated circulating MyD88, and increased NF-κB activity. IRAK-3 MI% correlated negatively with its transcript and positively with MyD88 and NF-κB activity. A logistic regression model was created to predict active demyelination. The C-index was 0.924, which indicates a very strong prediction model. Within the limitations of current work, IRAK-3 methylation level seems to be a promising candidate biomarker for identifying MS patients at risk of relapse.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110327"},"PeriodicalIF":4.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757541","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}
引用次数: 0
Novel insight into MDA-7/IL-24: A potent therapeutic target for autoimmune and inflammatory diseases 对 MDA-7/IL-24 的新认识:自身免疫性和炎症性疾病的强效治疗靶点
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-07-20 DOI: 10.1016/j.clim.2024.110322
Kangni Feng, Jiemei Cen, Xiaoling Zou, Tiantuo Zhang
{"title":"Novel insight into MDA-7/IL-24: A potent therapeutic target for autoimmune and inflammatory diseases","authors":"Kangni Feng,&nbsp;Jiemei Cen,&nbsp;Xiaoling Zou,&nbsp;Tiantuo Zhang","doi":"10.1016/j.clim.2024.110322","DOIUrl":"10.1016/j.clim.2024.110322","url":null,"abstract":"<div><p>Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24) is a pleiotropic member of the IL-10 family of cytokines, and is involved in multiple biological processes, including cell proliferation, cell differentiation, tissue fibrosis, the inflammatory response, and antitumor activity. MDA-7/IL-24 can regulate epithelial integrity, homeostasis, mucosal immunity and host resistance to various pathogens by enhancing immune and inflammatory responses. Our recent study revealed the mechanism of MDA-7/IL-24 in promoting airway inflammation and airway remodeling through activating the JAK/STAT3 and ERK signaling pathways in bronchial epithelial cells. Herein, we summarize the cellular sources, inducers, target cells, signaling pathways, and biological effects of MDA-7/IL-24 in several allergic and autoimmune diseases. This review also synopsizes recent advances in clinical research targeting MDA-7/IL-24 or its receptors. Based on these advancements, we emphasize its potential as a target for immunotherapy and discuss the challenges of developing immunotherapeutic drugs targeting MDA-7/IL-24 or its receptors in autoimmune and inflammatory disorders.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110322"},"PeriodicalIF":4.5,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733700","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}
引用次数: 0
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