Clinical immunology最新文献

{"title":"Resident synovial macrophages in synovial fluid: Implications for immunoregulation.","authors":"Karen I Cyndari, Breanna M Scorza, Zeb R Zacharias, Danielle Pessôa-Pereira, Leela Strand, Kurayi Mahachi, Juan Marcos Oviedo, Lisa Gibbs, Katherine L Butler, Graham Ausdal, Dylan Hendricks, Rika Yahashiri, Jacob M Elkins, Trevor Gulbrandsen, Andrew R Peterson, Michael C Willey, Keke C Fairfax, Christine A Petersen","doi":"10.1016/j.clim.2024.110422","DOIUrl":"https://doi.org/10.1016/j.clim.2024.110422","url":null,"abstract":"<p><p>Resident synovial macrophages (RSMs) are anti-inflammatory, self-renewing macrophages that provide physical immune sequestration of the joint space from the peripheral immune system. Increased permeability of this structure is associated with peripheral immune cells in the synovial fluid (SF). Direct measures of synovial barrier integrity are possible with tissue histology, but after barrier breakdown, if these cells perpetuate or initiate chronic inflammation in SF remains unknown. We sought to identify RSM in human SF as an indirect measure of synovial barrier integrity. To validate findings, we created a novel ex vivo explant model using human synovium. scRNA-seq revealed these SF RSMs upregulated pro-fibrotic and pro-osteoclastic pathways in inflammatory arthritis, but not septic arthritis. Increased frequencies of RSMs in SF was associated with increased sRANKL regardless of underlying pathology. These findings suggest the frequency of RSMs in SF may correlate with synovial barrier damage and in turn, potential damage to joint structures.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110422"},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863473","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}

{"title":"Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease.","authors":"Amin Alirezaylavasani, Ingrid Marie Egner, Børresdatter Dahl, Adity Chopra, Taissa de Matos Kasahara, Guro Løvik Goll, Jørgen Jahnsen, Gunnveig Grødeland, John Torgils Vaage, Fridtjof Lund-Johansen, Jan Cato Holter, Bente Halvorsen, Kristin Kaasen Jørgensen, Ludvig A Munthe, Hassen Kared","doi":"10.1016/j.clim.2024.110404","DOIUrl":"10.1016/j.clim.2024.110404","url":null,"abstract":"<p><p>Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110404"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791049","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}

{"title":"NADPH oxidase expression profile and PBMC immunophenotypic changes in anti-TNF-treated rheumatoid arthritis patients.","authors":"Tomasz Wysocki, Anna Wajda, Tomasz Kmiołek, Jakub Wroński, Magdalena Roszkowska, Marzena Olesińska, Agnieszka Paradowska-Gorycka","doi":"10.1016/j.clim.2024.110414","DOIUrl":"https://doi.org/10.1016/j.clim.2024.110414","url":null,"abstract":"<p><p>The aim of this research was to prospectively evaluate the impact of NOX2 gene expression profile (including NCF1, NCF2 and NCF4 genes) in peripheral blood mononuclear cells (PBMCs) on immune signatures, clinical characteristics and responsiveness to anti-TNF treatment in RA patients. Blood specimens were collected from 31 rheumatoid arthritis (RA) patients and 25 healthy controls, and 16 RA patients were followed at two timepoints during anti-TNF treatment. mRNA expression levels of selected genes and immunoregulatory cytokines concentrations were determined. We observed the significant upregulation of NCF4 and CD14 expression in RA group. The mRNA levels of NCF1 and CD14 positively correlated both in groups of RA patients and healthy controls. NOX2 gene expression profile was not associated with anti-TNF responsiveness, nor with RA clinical features. TNFα inhibition has not influenced NOX2 expression either. Notably, this study indicate the novel links between expression levels of NCF1 and monocyte differentiation antigen CD14.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"110414"},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791052","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}

{"title":"Corrigendum to “Immunomodulatory effect of Lactococcus lactis JCM5805 on human plasmacytoid dendritic cells” [Clinical Immunology 149/3PB (2013) 509–518]","authors":"Tetsu Sugimura ,&nbsp;Kenta Jounai ,&nbsp;Konomi Ohshio ,&nbsp;Takaaki Tanaka ,&nbsp;Masahiro Suwa ,&nbsp;Daisuke Fujiwara","doi":"10.1016/j.clim.2024.110382","DOIUrl":"10.1016/j.clim.2024.110382","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110382"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567246","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}

{"title":"Allergy and autoinflammation drive persistent systemic inflammatory response in Meniere Disease: A longitudinal study.","authors":"Lidia Frejo, Francisca E Cara, Marisa Flook, Paula Robles-Bolivar, Alba Escalera-Balsera, Maria Alharilla Montilla-Ibañez, Emilio Dominguez-Duran, Marta Martinez-Martinez, Patricia Perez-Carpena, Jose Antonio Lopez-Escamez","doi":"10.1016/j.clim.2024.110413","DOIUrl":"10.1016/j.clim.2024.110413","url":null,"abstract":"<p><strong>Background: </strong>Meniere disease (MD), an inner ear disorder influenced by genetic and environmental factors, potentially leads to chronic inflammation. This study evaluates whether inflammation in MD patients is driven by allergy or autoinflammation.</p><p><strong>Methods: </strong>2-year longitudinal study. Cytokine and chemokine levels were measured in plasma from 72 patients. Functional clusters were identified using weighted-based discriminant and km3d trajectory analyses. THP-1 cells were exposed to patients' plasma to assess macrophage polarization, and qPCR analyzed upstream cytokine release events.</p><p><strong>Results: </strong>Four groups were identified: 1) Autoimmune (20 %) with high TNF-α (p = 0.0004); 2) Allergic (25 %) with elevated IgE (p < 0.0001) and M2 polarization; 3) Autoinflammatory (13 %) with increased IL-1β (p < 0.0001), activated via CASP1/NLRP3; 4) Low cytokine levels (42 %; cytokines in Q1). Group stability was observed, with 36 % of allergic patients also showing high IL-1β.</p><p><strong>Conclusion: </strong>Identified immunophenotypes, allergy-driven IgE responses, and IL-1β-mediated autoinflammation indicate that targeting inflammation with biomarkers could optimize MD treatment and outcomes.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110413"},"PeriodicalIF":4.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766810","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}

{"title":"Single-cell analysis combined with transcriptome sequencing identifies autophagy hub genes in macrophages after spinal cord injury","authors":"Cheng Ju ,&nbsp;Renfeng Liu ,&nbsp;Yanming Ma ,&nbsp;Hui Dong ,&nbsp;Ruiqing Xu ,&nbsp;Huimin Hu ,&nbsp;Dingjun Hao","doi":"10.1016/j.clim.2024.110412","DOIUrl":"10.1016/j.clim.2024.110412","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a neurological disease characterized by the loss of motor and sensory function below the injury level. The pathogenesis of SCI is complex, involving the recruitment of various cells that play key roles in the injury area. Single-cell RNA sequencing (scRNA-seq) can analyze cell heterogeneity and inter-cell communication. Bulk RNA-seq offers advantages such as low cost, mature technology and high throughput. Joint analysis of bulk RNA-seq and scRNA-seqis more complementary for exploring the pathophysiology of diseases. In this study, we revealed changes in cell clusters and intercellular signaling after SCI through the scRNA-seq analysis. Bioinformatics analyses and experimental verification showed that macrophages increase rapidly and become the dominant cell type after SCI. The mTOR gene is the key molecule of M1 macrophage autophagy blockade and the PI3K-AKT-mTOR signaling pathway plays an important role in blockings macrophage autophagy.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110412"},"PeriodicalIF":4.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747979","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}

{"title":"Prolonged diagnostic journey in delayed-onset adenosine deaminase deficiency","authors":"Dan Tomomasa ,&nbsp;Masatoshi Takagi ,&nbsp;Ryohei Watanabe ,&nbsp;Ryosuke Wakatsuki ,&nbsp;Satoshi Miyamoto ,&nbsp;Akihiro Hoshino ,&nbsp;Takahiro Kamiya ,&nbsp;Takeshi Isoda ,&nbsp;Anju Kobayashi ,&nbsp;Kenjiro Kosaki ,&nbsp;Fumiaki Sakura ,&nbsp;Takaki Asano ,&nbsp;Toru Uchiyama ,&nbsp;Satoshi Okada ,&nbsp;Tomohiro Morio ,&nbsp;Hirokazu Kanegane","doi":"10.1016/j.clim.2024.110405","DOIUrl":"10.1016/j.clim.2024.110405","url":null,"abstract":"<div><div>Adenosine deaminase (ADA) deficiency typically presents as a severe combined immunodeficiency in early infancy, although its onset may be delayed in some cases. We encountered two patients diagnosed with ADA deficiency in adulthood. In addition to previously reported cases, we aimed to identify and characterize the clinical and immunological features associated with delayed- and late-onset ADA deficiency. Both patients presented with pneumonia and hypothyroidism during early childhood. The patients were subsequently treated with periodic immunoglobulin replacement and levothyroxine therapy. They experienced recurrent infections, including pneumonia and shingles, and were diagnosed with ADA deficiency in adulthood. A literature review revealed that patients diagnosed after the age of 10 years had a median interval of 18 years from disease onset to diagnosis. Patients with combined immunodeficiency and recurrent lower respiratory tract infections or autoimmune diseases require early measurement of ADA activity or genetic analysis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110405"},"PeriodicalIF":4.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726590","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}

{"title":"Characteristics of patients with low serum IgE levels and selective IgE deficiency: Data from an immunodeficiency referral center","authors":"Hilal Ünsal ,&nbsp;Ahsen Ekinci ,&nbsp;Gülnar Aliyeva ,&nbsp;Hacer Neslihan Bildik ,&nbsp;Saliha Esenboğa ,&nbsp;Deniz Çağdaş","doi":"10.1016/j.clim.2024.110403","DOIUrl":"10.1016/j.clim.2024.110403","url":null,"abstract":"<div><div>Low immunoglobulin E (IgE) levels are defined as values below 2.5 IU/mL. Selective IgE deficiency (sIgED) refers to reduced serum IgE levels in patients with normal IgA/G/M levels. We evaluated 677 patients with low IgE levels. Recurrent infections (78.8 %), a history of allergy (27.3 %), and autoimmune/inflammatory diseases (18.3 %) are common. The primary immunodeficiency disease (PID) (<em>n</em> = 483, 71.3 %) diagnoses include 313 (46.2 %) patients with antibody deficiency and 119 (17.6 %) with combined immunodeficiency. Genetic pathogenic variants were present in 154 out of 207 PID patients. Within sIgED group, 23 (19.8 %) had primary immunodeficiencies. We observed a high prevalence of autoimmune/inflammatory diseases, allergies, malignancies, and PID among patients with low IgE levels. Therefore, clinicians should be vigilant when evaluating patients with low IgE levels, as this finding may indicate an underlying systemic disease or PID.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110403"},"PeriodicalIF":4.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708865","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}

{"title":"Sympathetic nerve promotes renal fibrosis by activating M2 macrophages through β2-AR-Gsa","authors":"Lele Liu ,&nbsp;Yuanjun Deng ,&nbsp;Qian Li ,&nbsp;Yang Cai ,&nbsp;Chunjiang Zhang ,&nbsp;Tianjing Zhang ,&nbsp;Gang Xu ,&nbsp;Min Han","doi":"10.1016/j.clim.2024.110397","DOIUrl":"10.1016/j.clim.2024.110397","url":null,"abstract":"<div><div>Sympathetic nervous system overactivation is directly related to renal fibrosis. This study focused on the role of and mechanism by which sympathetic signaling regulates macrophage activation, as well as the contribution to renal fibrosis. Renal denervation alleviated tubular necrosis, tubulointerstitial fibrosis, and macrophage accumulation induced by unilateral ureteral obstruction and ischemia-reperfusion injury. In vitro, norepinephrine (NE) promoted macrophage alternative (M2) polarization by activating β2-adrenergic receptor (β2-AR) and heterotrimeric G stimulatory protein α-subunit (Gsa). The effects of NE-induced macrophage M2 polarization were blocked by a β2-AR selective antagonist and Gsa siRNA. Importantly, ablation of Gsa in macrophages alleviated tubulointerstitial fibrosis, macrophage accumulation, and M2 polarization in the renal ischemia-reperfusion injury model. Sympathetic nervous system overactivation regulates M2 polarization in macrophages as an important neuroimmune mechanism of renal fibrosis. The β2-AR-Gsa signaling pathway was responsible for NE-induced macrophage M2 polarization, which may be a therapeutic target for renal fibrosis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110397"},"PeriodicalIF":4.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695275","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}

{"title":"Comparative analysis of the B cell receptor repertoire during relapse and remission in patients with multiple sclerosis","authors":"Miriam Pérez-Saldívar ,&nbsp;Yusuke Nakamura ,&nbsp;Kazuma Kiyotani ,&nbsp;Seiya Imoto ,&nbsp;Kotoe Katayama ,&nbsp;Rui Yamaguchi ,&nbsp;Satoru Miyano ,&nbsp;Jesús Martínez-Barnetche ,&nbsp;Elizabeth Ernestina Godoy-Lozano ,&nbsp;Graciela Ordoñez ,&nbsp;Julio Sotelo ,&nbsp;Hugo González-Conchillos ,&nbsp;Adolfo Martínez-Palomo ,&nbsp;José Flores-Rivera ,&nbsp;Leopoldo Santos-Argumedo ,&nbsp;Erick Saúl Sánchez-Salguero ,&nbsp;Martha Espinosa-Cantellano","doi":"10.1016/j.clim.2024.110398","DOIUrl":"10.1016/j.clim.2024.110398","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic, multifactorial, inflammatory and demyelinating disease of the central nervous system (CNS), which involves an autoimmune response against components of the myelin sheaths. Anti-B cell therapies have been proven to be successful in reducing relapses. Therefore, the study of B cells in both phases of the disease (relapse and remission) is of great importance. Here, we analyzed peripheral blood-cell BCR repertoire from 11 MS patients during a relapse phase and during remission, 6 patients with other inflammatory neurological diseases (OIND) and 10 healthy subjects (HCs), using next generation sequencing. In addition, immunoglobulins G, M, A and D were quantified in the serum of patients and controls, using ELISA. BCR repertoire of relapsing MS patients showed lower diversity, as well as a higher rate of somatic hypermutation compared to the other study groups. Within this group, the highest percentage of shared clonotypes was observed. IGHV4–32 gene was identified as a potential differential biomarker between MS and OIND, as well as IGL3–21 gene as a potential MS biomarker. On the other hand, an elevation of IgG and IgD was found in the serum of MS patients during remission, and the serum IgG was also elevated in MS patients during relapse. In conclusion, these results show the important role of B cells in the pathogenesis of the MS relapses and a new panorama on the analysis of the peripheral blood BCR repertoire to obtain diagnostic tools for MS. Furthermore, this work highlights the need of studies in diverse populations, since results reported in Caucasian populations may not coincide with the immunological course of MS patients in other latitudes, due to differences in genetic background and environmental exposures.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110398"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646627","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}