Clinical immunology最新文献

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The anti-mCRP199–206 antibodies aggravate tubulointerstitial lesions in lupus nephritis 抗mCRP199-206抗体会加重狼疮肾炎的肾小管间质病变。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-09-03 DOI: 10.1016/j.clim.2024.110353
Mo Yuan , Ming-hui Zhao , Ying Tan
{"title":"The anti-mCRP199–206 antibodies aggravate tubulointerstitial lesions in lupus nephritis","authors":"Mo Yuan ,&nbsp;Ming-hui Zhao ,&nbsp;Ying Tan","doi":"10.1016/j.clim.2024.110353","DOIUrl":"10.1016/j.clim.2024.110353","url":null,"abstract":"<div><p>Tubulointerstitial lesions could also be prominent in lupus nephritis, and the pathogenesis of tubulointerstitial lesions may be different from glomerular lesions. Previous studies have showed that plasma antibodies against modified /monomeric C-reactive protein (mCRP) are associated with renal tubulointerstitial lesions in patients with lupus nephritis, and amino acid (aa) 199–206 was one of the major epitopes of mCRP. However, the role of anti-mCRP<sub>199–206</sub> antibodies in the pathogenesis of tubulointerstitial lesions in lupus nephritis is unknown. A total of 95 patients with renal biopsy-proven lupus nephritis were enrolled in this study. Plasma levels of anti-mCRP<sub>199–206</sub> antibodies were screened by enzyme-linked immunosorbent assay (ELISA). A lupus prone mouse model was immunized using peptides mCRP<sub>199–206</sub> to explore the potential role of anti-mCRP<sub>199–206</sub> antibodies in tubulointerstitial lesions. The mechanism of anti-mCRP<sub>199–206</sub> antibodies damage to renal tubular epithelial cells was investigated in vitro. Plasma antibodies against mCRP<sub>199–206</sub> were associated with renal tubulointerstitial lesions and prognosis in patients with lupus nephritis. Immunization with peptides mCRP<sub>199–206</sub> in lupus prone mice could aggravate tubulointerstitial lesions and drive tubulointerstitial inflammation and fibrosis. Anti-mCRP <sub>199–206</sub> antibodies could activate the TGF-β1/Smad3 signal pathway and induce tubular damage by binding with CRP. Circulating antibodies against mCRP<sub>199–206</sub> could be a biomarker to reveal tubulointerstitial lesion, and participate in the pathogenesis of tubulointerstitial lesions, which might provide a potential therapeutic target for lupus nephritis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110353"},"PeriodicalIF":4.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139500","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
De novo glomerulonephritis associated with IgA anti-GBM alloantibodies after kidney transplantation in Alport syndrome: A case report with diagnostic implications 阿尔波特综合征肾移植后与 IgA 抗 GBM 同种抗体相关的新生肾小球肾炎:具有诊断意义的病例报告。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-09-03 DOI: 10.1016/j.clim.2024.110354
Marina Segura-Guerrero , Carlos Saus , Roberto Gozalbo-Rovira , Sheila Cabello-Pelegrín , María Luisa Vargas , Natalia Martínez-Pomar , Jesús Rodríguez-Díaz , Juan Saus , Maria Rosa Julià
{"title":"De novo glomerulonephritis associated with IgA anti-GBM alloantibodies after kidney transplantation in Alport syndrome: A case report with diagnostic implications","authors":"Marina Segura-Guerrero ,&nbsp;Carlos Saus ,&nbsp;Roberto Gozalbo-Rovira ,&nbsp;Sheila Cabello-Pelegrín ,&nbsp;María Luisa Vargas ,&nbsp;Natalia Martínez-Pomar ,&nbsp;Jesús Rodríguez-Díaz ,&nbsp;Juan Saus ,&nbsp;Maria Rosa Julià","doi":"10.1016/j.clim.2024.110354","DOIUrl":"10.1016/j.clim.2024.110354","url":null,"abstract":"<div><p>Alport syndrome (AS) is a hereditary disorder caused by pathogenic variants in <em>COL4A3, COL4A4,</em> or <em>COL4A5</em> genes expressing α3, α4, and α5 chains of basement membrane type IV collagen (COL4). The triple-helical α3α4α5(IV) protomer is a major component of the mature glomerular basement membrane (GBM) whose defective formation in AS leads to structural GBM disruption and kidney dysfunction, often resulting in kidney replacement therapy. A genetically intact renal graft exposes the immune system to a non-tolerized α3α4α5(IV) component and an alloimmune response eventually ensues. So far, only IgG alloantibodies reacting against COL4 have been reported in AS alloimmune responses. Here, we report alloimmune glomerulonephritis mediated by IgA antibodies against the non-collagenous C-terminal domain 1 of the α5(IV) chain in a patient with autosomal recessive AS following a second kidney transplantation. The patient presented a not previously described biallelic variant in the <em>COL4A4</em> gene. Immunological, diagnostic, and clinical implications are discussed.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110354"},"PeriodicalIF":4.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139498","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
MAPK signaling pathway induced LOX-1+ polymorphonuclear myeloid-derived suppressor cells in biliary atresia MAPK 信号通路在胆道闭锁中诱导 LOX-1+ 多形核髓鞘源性抑制细胞。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2024-09-03 DOI: 10.1016/j.clim.2024.110355
Cheng Chen , Hezhen Wang , Lili Xu , Zhipeng Guo , Ming Fu , Huimin Xia , Qiuming He , Ruizhong Zhang , Juan He
{"title":"MAPK signaling pathway induced LOX-1+ polymorphonuclear myeloid-derived suppressor cells in biliary atresia","authors":"Cheng Chen ,&nbsp;Hezhen Wang ,&nbsp;Lili Xu ,&nbsp;Zhipeng Guo ,&nbsp;Ming Fu ,&nbsp;Huimin Xia ,&nbsp;Qiuming He ,&nbsp;Ruizhong Zhang ,&nbsp;Juan He","doi":"10.1016/j.clim.2024.110355","DOIUrl":"10.1016/j.clim.2024.110355","url":null,"abstract":"<div><p>Biliary atresia (BA) is a severe pediatric liver disease characterized by progressive bile duct destruction and fibrosis, leading to significant liver damage and frequently necessitating liver transplantation. This study elucidates the role of LOX-1<sup>+</sup> polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in BA pathogenesis and assesses their potential as non-invasive early diagnostic biomarkers. Using flow cytometry, immunofluorescence, and molecular profiling, we analyzed the expression and activity of these cells in peripheral blood and liver tissues from BA patients and controls. Our findings reveal a significant increase in the frequencies and function of LOX-1<sup>+</sup>PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1<sup>+</sup>PMN-MDSC in peripheral blood significantly positively correlate with liver function parameters in BA patients, demonstrating diagnostic performance comparable to traditional serum markers. These findings suggest that LOX-1<sup>+</sup>PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110355"},"PeriodicalIF":4.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139499","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 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
{"title":"The platelet-mitochondria nexus in autoimmune and musculoskeletal diseases","authors":"Despina Michailidou ,&nbsp;Stavros Giaglis ,&nbsp;George L. Dale","doi":"10.1016/j.clim.2024.110350","DOIUrl":"10.1016/j.clim.2024.110350","url":null,"abstract":"<div><p>Platelets are crucial for thrombosis and hemostasis. Importantly, they contain mitochondria that are responsible for energy generation and therefore vital for platelet survival and activation. Activated platelets can release mitochondria that may be free or encapsulated in platelet extracellular vesicles (EVs). Extruded mitochondria are a well-known source of mitochondrial DNA, and mitochondrial antigens that can be targeted by autoantibodies forming immune complexes (IC). Interaction of IC with the platelet cell surface FcγRIIA receptor results in platelet activation and release of platelet granule components. In this review, we summarize how platelets and mitochondria may contribute to the pathogenesis of different autoimmune and musculoskeletal diseases. Targeting key drivers of mitochondrial extrusion may ultimately lead to urgently needed targeted pharmacological interventions for treating inflammation and thrombotic diathesis, and halting organ damage in some of these rheumatological conditions.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"267 ","pages":"Article 110350"},"PeriodicalIF":4.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105027","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-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 ,&nbsp;Halemah AlSaeed ,&nbsp;Nourah Almansour ,&nbsp;Fahd Al-Mulla ,&nbsp;Yusuf A. Hannun ,&nbsp;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,&nbsp;M.C. Marcial-Medina,&nbsp;B.E. Ruiz-Medina,&nbsp;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 ,&nbsp;Giulio Olivieri ,&nbsp;Giuseppe Rubens Pascucci ,&nbsp;Donato Amodio ,&nbsp;Elena Morrocchi ,&nbsp;Chiara Pighi ,&nbsp;Emma Concetta Manno ,&nbsp;Gioacchino Andrea Rotulo ,&nbsp;Carolina D'Anna ,&nbsp;Marcello Chinali ,&nbsp;Isabella Tarissi de Jacobis ,&nbsp;Danilo Buonsenso ,&nbsp;Alberto Villani ,&nbsp;Paolo Rossi ,&nbsp;Alessandra Marchesi ,&nbsp;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 ,&nbsp;Naoya Inoue ,&nbsp;Yoshinori Iwatani ,&nbsp;Yuri Takeno ,&nbsp;Yuya Arakawa ,&nbsp;Yoh Hidaka ,&nbsp;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 ,&nbsp;Marsilio Adriani ,&nbsp;Pierre Dönnes ,&nbsp;Kirsty E. Waddington ,&nbsp;Coziana Ciurtin ,&nbsp;Eva Kubala Havrdova ,&nbsp;The ABIRISK Consortium ,&nbsp;Rachel Farrell ,&nbsp;Petra Nytrova ,&nbsp;Inés Pineda-Torra ,&nbsp;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 ,&nbsp;Hans Jakob Hartling ,&nbsp;Jon Gitz Holler ,&nbsp;Lars Klingen Gjærde ,&nbsp;Arnold Matovu Dungu ,&nbsp;Maria Elizabeth Engel Møller ,&nbsp;Rebecca Svanberg Teglgaard ,&nbsp;Carsten Utoft Utoft Niemann ,&nbsp;Patrick Terrence Brooks ,&nbsp;Trine H. Mogensen ,&nbsp;Nina Weis ,&nbsp;Daria Podlekareva ,&nbsp;Marie Louise Baum Jørgensen ,&nbsp;Anne Ortved Gang ,&nbsp;Ditte Stampe Hersby ,&nbsp;Annemette Hald ,&nbsp;Susanne Dam Nielsen ,&nbsp;Anne-Mette Lebech ,&nbsp;Marie Helleberg ,&nbsp;Jens Lundgren ,&nbsp;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
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