Clinical immunology最新文献_第9页

The platelet-mitochondria nexus in autoimmune and musculoskeletal diseases 自身免疫性疾病和肌肉骨骼疾病中的血小板-线粒体关系。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-30 DOI: 10.1016/j.clim.2024.110350

Despina Michailidou , Stavros Giaglis , George L. Dale

引用次数: 0

IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages IL-6R（跨信号）是载脂巨噬细胞中胆固醇反向转运的关键调节因子。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-30 DOI: 10.1016/j.clim.2024.110351

Fatema Al-Rashed , Halemah AlSaeed , Nourah Almansour , Fahd Al-Mulla , Yusuf A. Hannun , Rasheed Ahmad

{"title":"IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages","authors":"Fatema Al-Rashed , Halemah AlSaeed , Nourah Almansour , Fahd Al-Mulla , Yusuf A. Hannun , Rasheed Ahmad","doi":"10.1016/j.clim.2024.110351","DOIUrl":"10.1016/j.clim.2024.110351","url":null,"abstract":"<div><p>Atherosclerosis is a cardiovascular disease caused by cholesterol-laden arterial plaques. This study evaluated the correlation between interleukin-6 (IL-6), its receptors (IL6R/CD126), and glycoprotein 130 (gp130) alongside atherosclerosis biomarkers in a cohort of 142 subjects, equally divided between lean and obese individuals. Subsequent analyses used THP-1-derived macrophages to assess the biochemical impact of inhibiting IL-6 receptors. IL-6 secretion increased with atherosclerosis in obese subjects, while IL6R/CD126 and gp130 on monocytes decreased. Pharmacological gp130 inhibition altered lipid metabolism, increasing LDLR gene expression and cholesterol synthesis <em>via</em> SREBF2 and mevalonate kinase, along with HMG-CoA reductase at protein levels. gp130-deficient cells produced more cholesterol and had lower ABCA1 levels, suggesting hindered cholesterol efflux. Filipin III staining confirmed cholesterol retention in gp130-inhibited cells. <em>Ex-vivo</em> investigation on lean PBMCs further defined the impact of gp130 inhibition on the reduction of cholesterol efflux. Our results indicates gp130 is crucial for macrophage reverse cholesterol transport and may be a target for atherosclerosis treatments.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110351"},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004601/pdfft?md5=22f471ed6941bbcfb069a26de90108c6&pid=1-s2.0-S1521661624004601-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105026","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

IL-17 in skin infections and homeostasis 皮肤感染和稳态中的 Il-17。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-30 DOI: 10.1016/j.clim.2024.110352

M.G. García-Patiño, M.C. Marcial-Medina, B.E. Ruiz-Medina, P. Licona-Limón

{"title":"IL-17 in skin infections and homeostasis","authors":"M.G. García-Patiño, M.C. Marcial-Medina, B.E. Ruiz-Medina, P. Licona-Limón","doi":"10.1016/j.clim.2024.110352","DOIUrl":"10.1016/j.clim.2024.110352","url":null,"abstract":"<div><p>Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110352"},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004613/pdfft?md5=46bee76e2dde519e0b00cfa2b82925d8&pid=1-s2.0-S1521661624004613-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105025","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

Multi-modal immune dynamics of pre-COVID-19 Kawasaki Disease following intravenous immunoglobulin 静脉注射免疫球蛋白后，COVID-19 前川崎病的多模式免疫动态变化。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-24 DOI: 10.1016/j.clim.2024.110349

Nicola Cotugno , Giulio Olivieri , Giuseppe Rubens Pascucci , Donato Amodio , Elena Morrocchi , Chiara Pighi , Emma Concetta Manno , Gioacchino Andrea Rotulo , Carolina D'Anna , Marcello Chinali , Isabella Tarissi de Jacobis , Danilo Buonsenso , Alberto Villani , Paolo Rossi , Alessandra Marchesi , Paolo Palma

{"title":"Multi-modal immune dynamics of pre-COVID-19 Kawasaki Disease following intravenous immunoglobulin","authors":"Nicola Cotugno , Giulio Olivieri , Giuseppe Rubens Pascucci , Donato Amodio , Elena Morrocchi , Chiara Pighi , Emma Concetta Manno , Gioacchino Andrea Rotulo , Carolina D'Anna , Marcello Chinali , Isabella Tarissi de Jacobis , Danilo Buonsenso , Alberto Villani , Paolo Rossi , Alessandra Marchesi , Paolo Palma","doi":"10.1016/j.clim.2024.110349","DOIUrl":"10.1016/j.clim.2024.110349","url":null,"abstract":"<div><p>Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature. APBB1IP demonstrated an association with coronary artery involvement (CAI) and was significantly higher in CAI+ compared to CAI- patients. Integrative analysis revealed a transient reduction in CD4+ EM T cells and a comprehensive immune activation and exhaustion. Following treatment, Tregs at both frequency and gene expression levels revealed immune dynamics of recovery. Overall, our data provide insights into KD, which may offer valuable information on prognostic indicators and possible targets for novel treatments.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110349"},"PeriodicalIF":4.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072163","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

Effect of DNA methylation at the CTLA4 gene on the clinical status of autoimmune thyroid diseases CTLA4 基因的 DNA 甲基化对自身免疫性甲状腺疾病临床状况的影响。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-13 DOI: 10.1016/j.clim.2024.110338

Hiroki Ohtani , Naoya Inoue , Yoshinori Iwatani , Yuri Takeno , Yuya Arakawa , Yoh Hidaka , Mikio Watanabe

{"title":"Effect of DNA methylation at the CTLA4 gene on the clinical status of autoimmune thyroid diseases","authors":"Hiroki Ohtani , Naoya Inoue , Yoshinori Iwatani , Yuri Takeno , Yuya Arakawa , Yoh Hidaka , Mikio Watanabe","doi":"10.1016/j.clim.2024.110338","DOIUrl":"10.1016/j.clim.2024.110338","url":null,"abstract":"<div><p>The pathogenesis and manifestation of autoimmune thyroid diseases (AITDs), Graves' disease (GD), and Hashimoto's disease (HD) are associated with T cell activation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a crucial role in the regulation of T cell activation. DNA methylation levels of eight CpG sites in the <em>CTLA4</em> gene and expression levels of soluble CTLA-4 were examined. Methylation levels of +22 CpG and CT60 CpG-SNPs in patients with GD and HD with the CT60 GG genotype were lower than those in control subjects. Methylation levels of the-15 CpG sites were lower in patients with intractable GD than those in GD patients in remission. These results suggest that demethylation of +22 CpG and CT60 CpG-SNPs may be associated with susceptibility to GD and HD in subjects with the <em>CTLA4</em> CT60 GG genotype, and that demethylation of −15 CpG may be associated with the intractability of GD.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110338"},"PeriodicalIF":4.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004479/pdfft?md5=0c1dbb4895daac5324e81618f423b492&pid=1-s2.0-S1521661624004479-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981863","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

Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity 对干扰素-β产生免疫原性的多发性硬化症患者在治疗前有不同的转录组和蛋白质组特征，这些特征与疾病的严重程度有关。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-11 DOI: 10.1016/j.clim.2024.110339

Leda Coelewij , Marsilio Adriani , Pierre Dönnes , Kirsty E. Waddington , Coziana Ciurtin , Eva Kubala Havrdova , The ABIRISK Consortium , Rachel Farrell , Petra Nytrova , Inés Pineda-Torra , Elizabeth C. Jury

{"title":"Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity","authors":"Leda Coelewij , Marsilio Adriani , Pierre Dönnes , Kirsty E. Waddington , Coziana Ciurtin , Eva Kubala Havrdova , The ABIRISK Consortium , Rachel Farrell , Petra Nytrova , Inés Pineda-Torra , Elizabeth C. Jury","doi":"10.1016/j.clim.2024.110339","DOIUrl":"10.1016/j.clim.2024.110339","url":null,"abstract":"<div><p>Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, and patients were stratified at baseline according to their M12 ADA-status (ADA-positive/ADA-negative). Patients stratified as ADA-positive were characterised by an early dampened response to interferon-beta (prior to serum ADA detection) and distinct proinflammatory transcriptomic/proteomic peripheral blood signatures enriched for ‘immune response activation’ including phosphoinositide 3-kinase-γ and NFκB-signalling pathways both at baseline and throughout the treatment course, compared to ADA-negative patients. These immunogenicity-associated proinflammatory signatures significantly overlapped with signatures of MS disease severity. Thus, whole blood molecular profiling is a promising tool for prediction of ADA-development in RRMS and could provide insight into mechanisms of immunogenicity.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110339"},"PeriodicalIF":4.5,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004480/pdfft?md5=cf7edb1941aec6502a229fe34b86a837&pid=1-s2.0-S1521661624004480-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975252","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

Deep immune cell phenotyping and induced immune cell responses at admission stratified by BMI in patients hospitalized with COVID-19: An observational multicenter cohort pilot study COVID-19住院患者入院时按体重指数分层的深度免疫细胞表型和诱导免疫细胞反应：一项观察性多中心队列试点研究。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-06 DOI: 10.1016/j.clim.2024.110336

Adin Sejdic , Hans Jakob Hartling , Jon Gitz Holler , Lars Klingen Gjærde , Arnold Matovu Dungu , Maria Elizabeth Engel Møller , Rebecca Svanberg Teglgaard , Carsten Utoft Utoft Niemann , Patrick Terrence Brooks , Trine H. Mogensen , Nina Weis , Daria Podlekareva , Marie Louise Baum Jørgensen , Anne Ortved Gang , Ditte Stampe Hersby , Annemette Hald , Susanne Dam Nielsen , Anne-Mette Lebech , Marie Helleberg , Jens Lundgren , Birgitte Lindegaard

{"title":"Deep immune cell phenotyping and induced immune cell responses at admission stratified by BMI in patients hospitalized with COVID-19: An observational multicenter cohort pilot study","authors":"Adin Sejdic , Hans Jakob Hartling , Jon Gitz Holler , Lars Klingen Gjærde , Arnold Matovu Dungu , Maria Elizabeth Engel Møller , Rebecca Svanberg Teglgaard , Carsten Utoft Utoft Niemann , Patrick Terrence Brooks , Trine H. Mogensen , Nina Weis , Daria Podlekareva , Marie Louise Baum Jørgensen , Anne Ortved Gang , Ditte Stampe Hersby , Annemette Hald , Susanne Dam Nielsen , Anne-Mette Lebech , Marie Helleberg , Jens Lundgren , Birgitte Lindegaard","doi":"10.1016/j.clim.2024.110336","DOIUrl":"10.1016/j.clim.2024.110336","url":null,"abstract":"<div><h3>Introduction</h3><p>Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients.</p></div><div><h3>Methods and results</h3><p>This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls.</p></div><div><h3>Conclusions</h3><p>Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110336"},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004455/pdfft?md5=ef1ffd1c122f7cb2e1e63c9acfb958cd&pid=1-s2.0-S1521661624004455-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906112","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

Mechanisms of age-related Treg dysfunction in an arthritic environment 关节炎环境中与年龄相关的 Treg 功能障碍的机制

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-05 DOI: 10.1016/j.clim.2024.110337

Taihei Nishiyama , Ayako Ohyama , Haruka Miki , Hiromitsu Asashima , Yuya Kondo , Hiroto Tsuboi , Hiroshi Ohno , Hitoshi Shimano , Isao Matsumoto

引用次数: 0

Anti-IL12p40 autoantibodies in a teenage girl with multiple recurrent abscesses 一名患有多发性脓肿的少女体内的抗IL12p40自身抗体。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-03 DOI: 10.1016/j.clim.2024.110335

Ana Paola Macias Robles , Aristine Cheng , Steven M. Holland , Saul O. Lugo Reyes

{"title":"Anti-IL12p40 autoantibodies in a teenage girl with multiple recurrent abscesses","authors":"Ana Paola Macias Robles , Aristine Cheng , Steven M. Holland , Saul O. Lugo Reyes","doi":"10.1016/j.clim.2024.110335","DOIUrl":"10.1016/j.clim.2024.110335","url":null,"abstract":"<div><p>More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. <em>Mycobacterium tuberculosis</em> was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110335"},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888642","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 role of neutrophils in autoimmune diseases 中性粒细胞在自身免疫性疾病中的作用

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-08-02 DOI: 10.1016/j.clim.2024.110334

Zhuoshu Li , Qianjin Lu

引用次数: 0