Clinical immunology最新文献_第7页

Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns 从 DNA 甲基化模式看罕见特纳综合征与狼疮的共存。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-14 DOI: 10.1016/j.clim.2024.110310

Gülşah Kavrul Kayaalp , Desiré Casares-Marfil , Sezgin Şahin , Özgür Kasapçopur , Betül Sözeri , Nuray Aktay Ayaz , Amr H. Sawalha

{"title":"Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns","authors":"Gülşah Kavrul Kayaalp , Desiré Casares-Marfil , Sezgin Şahin , Özgür Kasapçopur , Betül Sözeri , Nuray Aktay Ayaz , Amr H. Sawalha","doi":"10.1016/j.clim.2024.110310","DOIUrl":"10.1016/j.clim.2024.110310","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110310"},"PeriodicalIF":4.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004194/pdfft?md5=22bca384a0e1a66de9ab61fc2624456e&pid=1-s2.0-S1521661624004194-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619500","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

Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis 腺苷 A2A 受体活化调节 M1 巨噬细胞的活化，从而启动银屑病的先天性免疫和适应性免疫。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-11 DOI: 10.1016/j.clim.2024.110309

Yan Lu , Wu Zhu , Guan Xiong Zhang , Jun Chen Chen , Qiao Lin Wang , Man Yun Mao , Si Chun Deng , Li Ping Jin , Hong Liu , Ye Hong Kuang

{"title":"Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis","authors":"Yan Lu , Wu Zhu , Guan Xiong Zhang , Jun Chen Chen , Qiao Lin Wang , Man Yun Mao , Si Chun Deng , Li Ping Jin , Hong Liu , Ye Hong Kuang","doi":"10.1016/j.clim.2024.110309","DOIUrl":"10.1016/j.clim.2024.110309","url":null,"abstract":"<div><p>Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110309"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603325","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

Neutrophil extracellular traps promote macrophage inflammation in psoriasis 中性粒细胞胞外捕获物会促进银屑病巨噬细胞的炎症反应。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-11 DOI: 10.1016/j.clim.2024.110308

Ruolin Li , Yunjie Xiong , Linqiang Ma , Chuan Peng , Shuangxin Qi , Rufei Gao , Ping Wang , Fengzeng Li , Junlong Li , Qifu Li , Aijun Chen

{"title":"Neutrophil extracellular traps promote macrophage inflammation in psoriasis","authors":"Ruolin Li , Yunjie Xiong , Linqiang Ma , Chuan Peng , Shuangxin Qi , Rufei Gao , Ping Wang , Fengzeng Li , Junlong Li , Qifu Li , Aijun Chen","doi":"10.1016/j.clim.2024.110308","DOIUrl":"10.1016/j.clim.2024.110308","url":null,"abstract":"<div><p>Psoriasis is a chronic inflammatory skin disease connected with immune dysregulation. Macrophages are key inflammatory cells in psoriasis but the specific mechanism of their activation is not fully understood. Neutrophil extracellular traps (NETs) have been shown to regulate macrophage function. Here, we found that NET deposition was increased in psoriasis lesions. Peptidylarginine deaminase 4 (PAD4, a key enzyme for NET formation) deficiency attenuated skin lesions and inflammation in an imiquimod-induced psoriatic mouse model. Furthermore, the STING signaling pathway was markedly activated in psoriasis and abolished by PAD4 deficiency. PAD4-deficient mice treated with the STING agonist DMXAA exhibited more severe symptoms and inflammation than control mice. Mechanistically, the STING inhibitor C-176 inhibited NET-induced macrophage inflammation and further inhibited the proliferation of HaCaT cells. Our findings suggest an important role of NETs in the pathogenesis of psoriasis, and activation of macrophage STING/NF-κB signaling pathway might involve in NETs related psoriasis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110308"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603327","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

Necroptosis and autoimmunity 坏死与自身免疫。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-11 DOI: 10.1016/j.clim.2024.110313

Lin Peng

引用次数: 0

Acute kidney injury following chimeric antigen receptor T-cell therapy: Epidemiology, mechanism and prognosis 嵌合抗原受体 T 细胞疗法后的急性肾损伤：流行病学、机制和预后。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-10 DOI: 10.1016/j.clim.2024.110311

引用次数: 0

Store-operated calcium entry dysfunction in CRAC channelopathy: Insights from a novel STIM1 mutation CRAC 通道病中的储能钙离子进入功能障碍：新型 STIM1 基因突变的启示

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-06 DOI: 10.1016/j.clim.2024.110306

Benedicte Alary , Pascal Cintas , Corentin Claude , Olivier Dellis , Corinne Thèze , Charles Van Goethem , Mireille Cossée , Martin Krahn , Valérie Delague , Marc Bartoli

{"title":"Store-operated calcium entry dysfunction in CRAC channelopathy: Insights from a novel STIM1 mutation","authors":"Benedicte Alary , Pascal Cintas , Corentin Claude , Olivier Dellis , Corinne Thèze , Charles Van Goethem , Mireille Cossée , Martin Krahn , Valérie Delague , Marc Bartoli","doi":"10.1016/j.clim.2024.110306","DOIUrl":"10.1016/j.clim.2024.110306","url":null,"abstract":"<div><p>Store-operated calcium entry (SOCE) plays a crucial role in maintaining cellular calcium homeostasis. This mechanism involves proteins, such as stromal interaction molecule 1 (STIM1) and ORAI1. Mutations in the genes encoding these proteins, especially STIM1, can lead to various diseases, including CRAC channelopathies associated with severe combined immunodeficiency. Herein, we describe a novel homozygous mutation, NM_003156 c.792-3C > G, in <em>STIM1</em> in a patient with a clinical profile of CRAC channelopathy, including immune system deficiencies and muscle weakness. Functional analyses revealed three distinct spliced forms in the patient cells: wild-type, exon 7 skipping, and intronic retention. Calcium influx analysis revealed impaired SOCE in the patient cells, indicating a loss of STIM1 function. We developed an antisense oligonucleotide treatment that improves <em>STIM1</em> splicing and highlighted its potential as a therapeutic approach. Our findings provide insights into the complex effects of <em>STIM1</em> mutations and shed light on the multifaceted clinical presentation of the patient.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110306"},"PeriodicalIF":4.5,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004157/pdfft?md5=598d2d3cc8fdad3fd207d9ab0d1e7045&pid=1-s2.0-S1521661624004157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558267","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

Metabolomic and lipidomic fingerprints in inflammatory skin diseases – Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis 炎症性皮肤病中的代谢组学和脂质组学指纹--特应性皮炎、化脓性扁桃体炎和斑块状银屑病的系统照明。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-05 DOI: 10.1016/j.clim.2024.110305

S. Rischke , S.M.G. Schäfer , A. König , T. Ickelsheimer , M. Köhm , L. Hahnefeld , A. Zaliani , K. Scholich , A. Pinter , G. Geisslinger , F. Behrens , R. Gurke

{"title":"Metabolomic and lipidomic fingerprints in inflammatory skin diseases – Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis","authors":"S. Rischke , S.M.G. Schäfer , A. König , T. Ickelsheimer , M. Köhm , L. Hahnefeld , A. Zaliani , K. Scholich , A. Pinter , G. Geisslinger , F. Behrens , R. Gurke","doi":"10.1016/j.clim.2024.110305","DOIUrl":"10.1016/j.clim.2024.110305","url":null,"abstract":"<div><p>Auto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110305"},"PeriodicalIF":4.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004145/pdfft?md5=72255d2f3023b416d5ed14820582bb3f&pid=1-s2.0-S1521661624004145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554298","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

Macrophage activation and inflammatory priming by anti-MAA antibodies in rheumatoid arthritis 类风湿性关节炎中抗 MAA 抗体对巨噬细胞的激活作用和炎症诱导。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-03 DOI: 10.1016/j.clim.2024.110303

Marcelo Afonso , Jitong Sun , Koji Sakuraba , Alexandra Cîrciumaru , Denis Lagutkin , Maša Filipović , Anca I. Catrina , Caroline Grönwall , Aase Hensvold , Bence Réthi

{"title":"Macrophage activation and inflammatory priming by anti-MAA antibodies in rheumatoid arthritis","authors":"Marcelo Afonso , Jitong Sun , Koji Sakuraba , Alexandra Cîrciumaru , Denis Lagutkin , Maša Filipović , Anca I. Catrina , Caroline Grönwall , Aase Hensvold , Bence Réthi","doi":"10.1016/j.clim.2024.110303","DOIUrl":"10.1016/j.clim.2024.110303","url":null,"abstract":"<div><p>We studied the effects of rheumatoid arthritis (RA) autoantibodies that target malondialdehyde-acetaldehyde protein adducts (anti-MAA) on inflammation and macrophage functions. We detected a profound reprogramming of gene expressions and the production of chemokines, such as CCL22 and CCL24, in anti-MAA exposed macrophages. Moreover, anti-MAA pretreatment promoted a more inflammatory cytokine profile upon TLR activation. Although anti-MAA are typically multi-reactive, we observed a prominent clonal diversity in inducing macrophage activation. Anti-MAA antibodies were not arthritogenic in mice, but altered a set of cytokine and growth factor encoding genes in the joints. In individuals at risk of RA anti-MAA IgG levels correlated with circulating inflammatory mediators prior to and at arthritis onset. Certain IgG anti-MAA clones may thus contribute to an inflammatory priming of the joint prior to the onset of systemic inflammation via inducing FcγR-mediated macrophage pre-activation and setting the stage for augmented responses to subsequent inflammatory stimuli.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110303"},"PeriodicalIF":4.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004121/pdfft?md5=c455424ea332b91cc0df91c01f59f5fc&pid=1-s2.0-S1521661624004121-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537615","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

CLADIN- CLADribine and INnate immune response in multiple sclerosis – A phase IV prospective study 多发性硬化症中的 CLADIN- CLADribine 和 INnate 免疫反应--一项 IV 期前瞻性研究。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-07-02 DOI: 10.1016/j.clim.2024.110304

Mastura Monif , Richard P. Sequeira , Andrea Muscat , Sian Stuckey , Paul G. Sanfilippo , Viet Minh , Naomi Loftus , Veronica Voo , Katherine Fazzolari , Melinda Moss , Vicki E. Maltby , Ai-Lan Nguyen , Robb Wesselingh , Nabil Seery , Cassie Nesbitt , Josephine Baker , Chris Dwyer , Lisa Taylor , Louise Rath , Anneke Van der Walt , Helmut Butzkueven

{"title":"CLADIN- CLADribine and INnate immune response in multiple sclerosis – A phase IV prospective study","authors":"Mastura Monif , Richard P. Sequeira , Andrea Muscat , Sian Stuckey , Paul G. Sanfilippo , Viet Minh , Naomi Loftus , Veronica Voo , Katherine Fazzolari , Melinda Moss , Vicki E. Maltby , Ai-Lan Nguyen , Robb Wesselingh , Nabil Seery , Cassie Nesbitt , Josephine Baker , Chris Dwyer , Lisa Taylor , Louise Rath , Anneke Van der Walt , Helmut Butzkueven","doi":"10.1016/j.clim.2024.110304","DOIUrl":"10.1016/j.clim.2024.110304","url":null,"abstract":"<div><p>Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact on the P2X7 receptor. There was a significant reduction in monocyte count <em>in vivo</em> at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ ‘non-classical’ monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. <em>In vitro</em>, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110304"},"PeriodicalIF":4.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533852","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

Bridging therapy-induced phenotypes and genetic immune dysregulation to study interleukin-2-induced immunotoxicology 连接治疗诱导表型和遗传免疫失调，研究白细胞介素-2诱导的免疫毒理学。

IF 4.5 3区医学

Clinical immunology Pub Date : 2024-06-29 DOI: 10.1016/j.clim.2024.110288

{"title":"Bridging therapy-induced phenotypes and genetic immune dysregulation to study interleukin-2-induced immunotoxicology","authors":"","doi":"10.1016/j.clim.2024.110288","DOIUrl":"10.1016/j.clim.2024.110288","url":null,"abstract":"<div><p>Interleukin-2 (IL-2) holds promise for the treatment of cancer and autoimmune diseases, but its high-dose usage is associated with systemic immunotoxicity. Differential IL-2 receptor (IL-2R) regulation might impact function of cells upon IL-2 stimulation, possibly inducing cellular changes similar to patients with hypomorphic <em>IL2RB</em> mutations, presenting with multiorgan autoimmunity. Here, we show that sustained high-dose IL-2 stimulation of human lymphocytes drastically reduces IL-2Rβ surface expression especially on T cells, resulting in impaired IL-2R signaling which correlates with high IL-2Rα baseline expression. IL-2R signaling in NK cells is maintained. CD4+ T cells, especially regulatory T cells are more broadly affected than CD8+ T cells, consistent with lineage-specific differences in IL-2 responsiveness. Given the resemblance of cellular characteristics of high-dose IL-2-stimulated cells and cells from patients with IL-2Rβ defects, impact of continuous IL-2 stimulation on IL-2R signaling should be considered in the onset of clinical adverse events during IL-2 therapy.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110288"},"PeriodicalIF":4.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003978/pdfft?md5=163cd96bd24b7212bfec316b96897c81&pid=1-s2.0-S1521661624003978-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476098","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