Rhea Bhargava , Hao Li , Kayaho Maeda , Maria G. Tsokos , George C. Tsokos
{"title":"Calcium calmodulin kinase IV deficiency in podocytes prevents the development of lupus nephritis","authors":"Rhea Bhargava , Hao Li , Kayaho Maeda , Maria G. Tsokos , George C. Tsokos","doi":"10.1016/j.clim.2025.110427","DOIUrl":"10.1016/j.clim.2025.110427","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ involvement including the kidney. Calcium/calmodulin-dependent protein kinase IV (CaMK4) has been shown to conrol immune cell nad podocyte function. To address the effect of genetic podocyte-specific CaMK4 deficiency on systemic autoimmunity and kidney pathology in lupus-prone mice we generated B6.<em>lpr.Camk4</em> <sup><em>flox</em></sup><em>.</em><sup><em>.</em></sup><em>podocin</em><sup><em>cre</em></sup> mice. Although podocyte-specific CaMK4 deletion in the lupus-prone Br.<em>lpr</em> mice did not affect systemic autoimmune response parameters, it led to significant improvement of kidney pathology and clinical outcomes. Specifically, B6.<em>lpr.Camk4</em> <sup><em>flox</em></sup><em>.</em><sup><em>.</em></sup><em>podocin</em><sup><em>cre</em></sup> mice exhibited reduced glomerular pathology, characterized by less mesangial cell proliferation and diminished immune complex deposition, accompanied by decreased levels of albuminuria and improved creatinine levels. CaMK4 deficiency in podocytes averted the deposition of immune complexes in the kidney. Interestingly, we found increased deposition of immune complexes in the liver. We conclude that CaMK4 expression in podocytes is central to the development of LN and its targeted deletion in podocytes prevents its development without affecting systemic autoimmunity while immune complexes appear to be re-directed from the kidney to the liver.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110427"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964043","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}
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
{"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":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Four groups were identified: 1) Autoimmune (20 %) with high TNF-α (<em>p</em> = 0.0004); 2) Allergic (25 %) with elevated IgE (<em>p</em> < 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.</div></div><div><h3>Conclusion</h3><div>Identified immunophenotypes, allergy-driven IgE responses, and IL-1β-mediated autoinflammation indicate that targeting inflammation with biomarkers could optimize MD treatment and outcomes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"271 ","pages":"Article 110413"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Vizcaino-Castro , Shipeng Chen , Baukje Nynke Hoogeboom , Annemarie Boerma , Toos Daemen , Cesar Oyarce
{"title":"Effect of repurposed metabolic drugs on human macrophage polarization and antitumoral activity","authors":"Ana Vizcaino-Castro , Shipeng Chen , Baukje Nynke Hoogeboom , Annemarie Boerma , Toos Daemen , Cesar Oyarce","doi":"10.1016/j.clim.2025.110440","DOIUrl":"10.1016/j.clim.2025.110440","url":null,"abstract":"<div><h3>Aim</h3><div>This study aimed to investigate whether the polarization of monocyte-derived macrophages towards an anti-inflammatory phenotype could be hindered by modulating cellular metabolism. Several metabolic drugs were selected: Perhexiline (PerHx) and Nitazoxanide (NTZ) targeting fatty acid oxidation, CB839 (Telaglenastat) targeting glutaminolysis and Metformin (Metf) targeting the mitochondrial electron transport chain.</div></div><div><h3>Results</h3><div>Our findings demonstrate that the presence of PerHx, NTZ, and CB839 during IL-4-mediated macrophages polarization impaired the acquisition of full anti-inflammatory phenotype, as evidenced by reduced expression of CD163 and CD209 and decreased secretion of CCL17 chemokine. Besides, CB839 induced tumoricidal activity in macrophages, comparable to that observed in macrophages activated by LPS and IFNγ.</div></div><div><h3>Conclusion</h3><div>This study reveals that targeting glutamine metabolism with CB839 effectively blocks the IL-4-induced anti-inflammatory phenotype in macrophages and enhances their tumor-killing capability. Our results provide a compelling rationale for repurposing metabolic drugs to create a pro-inflammatory tumor microenvironment, thereby potentially enhancing the efficacy of current immunotherapies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110440"},"PeriodicalIF":4.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074068","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}
Lixin Yue , Pei Qiao , Xia Li , Ke Xue , Bingyu Pang , Yaxing Bai , Pu Song , Huanhuan Qu , Hongjiang Qiao , Danni Sun , Xingan Wu , Rongrong Liu , Gang Wang , Erle Dang
{"title":"NLRX1 deficiency exacerbates skin inflammation in atopic dermatitis by disrupting mitophagy","authors":"Lixin Yue , Pei Qiao , Xia Li , Ke Xue , Bingyu Pang , Yaxing Bai , Pu Song , Huanhuan Qu , Hongjiang Qiao , Danni Sun , Xingan Wu , Rongrong Liu , Gang Wang , Erle Dang","doi":"10.1016/j.clim.2025.110442","DOIUrl":"10.1016/j.clim.2025.110442","url":null,"abstract":"<div><div>NLRX1 is an important regulator of inflammatory signaling in innate immune cells. Recent studies indicate NLRX1 activation may be a novel mechanism for inflammatory diseases, however, it has not been explored in atopic dermatitis (AD). Our study aims to investigate the potential role of NLRX1 in the pathogenesis of AD. We observed a significant decrease in NLRX1 expression in AD skin lesions and MC903-indued AD dermatitis. NLRX1 deficiency exacerbated AD inflammation, characterized by increased skin thickness, exacerbated inflammatory infiltration, and compromised skin barrier function. Mechanistically, NLRX1 regulated TSLP expression through Parkin-PINK1-mediated mitophagy in keratinocytes. Furthermore, topical application of NLRX1 agonist alleviated AD progression, including reduced ear thickness, diminished redness, and improved skin barrier function. This study provides novel insights into the regulatory role of NLRX1 in skin inflammation in AD, highlighting the potential therapeutic implications of targeting NLRX1 and mitophagy in AD treatment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110442"},"PeriodicalIF":4.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064091","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}
Minghua Zhan , Ziyao Li , Jianing Chen , Yanling Zhao , Zhou Bai , Binghuai Lu , Hongbin Chen , Yudong Liu
{"title":"Indoxyl sulfate (IS) mediates pro-inflammatory responses in severe pneumonia in patients with rheumatoid arthritis associated interstitial lung disease","authors":"Minghua Zhan , Ziyao Li , Jianing Chen , Yanling Zhao , Zhou Bai , Binghuai Lu , Hongbin Chen , Yudong Liu","doi":"10.1016/j.clim.2025.110430","DOIUrl":"10.1016/j.clim.2025.110430","url":null,"abstract":"<div><h3>Object</h3><div>Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have a high risk of serious infection, in particular severe pneumonia. This study aimed to investigate the transcriptional landscape, lower respiratory tract (LRT) microbiome and metabolomic profiles in the lung of RA-ILD patients with pneumonia.</div></div><div><h3>Method</h3><div>A total of 10 RA-ILD with pneumonia were enrolled in this study. In addition, 11 patients with COVID-19-associated pneumonia and 6 patients with non-autoimmune and non-COVID-19-related ILD with pneumonia were included as controls. Bronchoalveolar lavage fluid (BALF) was collected and prepared for metagenomic next-generation sequencing (mNGS), non-targeted metabolomics and bulk RNA-seq.</div></div><div><h3>Result</h3><div>Neutrophil-related genes were shared in the BALF cells of RA-ILD patients with pneumonia and patients with COVID-19-associated pneumonia. <em>Carnobacterium, Wujia, Intestinimonas, Apibacter, Anaerotignum</em> and <em>Parvimonas</em> were enriched in the LRT microbiome of RA-ILD, while <em>Wujia, Apibacter, Pseudocitrobacter</em>, and <em>Thermobacillus</em> were enriched in the LRT microbiome of COVID-19. Metabolomics analysis of BALF revealed significant elevation of indoxyl sulfate (IS) in the BALF of RA-ILD patients in comparison to COVID-19. Mechanistically, IS exerts an pro-inflammatory effect on macrophages and bronchial epithelial cells for pro-inflammatory cytokine production and potentiated neutrophils for neutrophil extracellular traps (NETs) formation.</div></div><div><h3>Conclusions</h3><div>Our results demonstrated a significant differences in the LRT microbiome and BALF metabolites between RA-ILD and COVID-19 patients with pneumonia, although they displayed similar local immune responses against lung infection. Alterations of LRT microbiome and related metabolites may be implicated in the pathogenesis of pneumonia in RA-ILD.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110430"},"PeriodicalIF":4.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058189","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}
Jingjing Song, Zhen Liu, Fan Yang, Ting Zhang, Zhenglun Pan
{"title":"Hypomethylation of the low-density lipoprotein receptor class A domain containing 4 gene in rheumatoid arthritis","authors":"Jingjing Song, Zhen Liu, Fan Yang, Ting Zhang, Zhenglun Pan","doi":"10.1016/j.clim.2025.110441","DOIUrl":"10.1016/j.clim.2025.110441","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease linked to epigenetic changes, particularly DNA methylation. While LDLRAD4 has been implicated in RA through GWAS, its role in RA via methylation remains unclear.</div></div><div><h3>Objectives</h3><div>To investigate LDLRAD4 methylation patterns in RA and evaluate its potential as a diagnostic and inflammatory biomarker.</div></div><div><h3>Methods</h3><div>We assessed DNA methylation at specific CpG sites within LDLRAD4 in 150 RA patients and 150 healthy controls. Clinical data, including disease duration and inflammatory markers, were collected.</div></div><div><h3>Results</h3><div>RA patients showed significant hypomethylation of LDLRAD4, especially in the LDLRAD4–43 and LDLRAD4–44 regions. ROC analysis yielded an AUC of 0.841, indicating strong diagnostic potential. Methylation levels correlated negatively with ESR, CRP and DAS28 in the RF+/CCP- subgroup.</div></div><div><h3>Conclusions</h3><div>LDLRAD4 DNA present hypomethylation in rheumatoid arthritis, and methylation levels are correlated with inflammatory indicator, possibly via TGF-β signaling. Further research is needed to explore its therapeutic potential.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110441"},"PeriodicalIF":4.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051686","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}
Mengting Liu , Ye Zhu , Weida Meng , Caiyan Zhang , Yuke Chen , Qi Shi , Sun Song , Shan Zheng , Yun Liu , Yufeng Zhou , Gong Chen
{"title":"Potential therapeutic effect of dimethyl fumarate on Treg/Th17 cell imbalance in biliary atresia","authors":"Mengting Liu , Ye Zhu , Weida Meng , Caiyan Zhang , Yuke Chen , Qi Shi , Sun Song , Shan Zheng , Yun Liu , Yufeng Zhou , Gong Chen","doi":"10.1016/j.clim.2025.110439","DOIUrl":"10.1016/j.clim.2025.110439","url":null,"abstract":"<div><div>The imbalance between Tregs and proinflammatory Th17 cells in children with biliary atresia (BA) causes immune damage to cholangiocytes. Dimethyl fumarate (DMF), an immunomodulatory drug, regulates the Treg/Th17 balance in diseases like multiple sclerosis (MS). This study explores DMF's effect on Treg/Th17 balance in BA and its potential mechanism. The differential gene expression profiles in liver of BA and choledochal cyst (CC) patients were analyzed by single-cell RNA sequencing (scRNA-seq). Treg and Th17 cell frequencies in BA hilar lymph nodes (LNs) were determined by flow cytometry. CD3<sup>+</sup> T cells were isolated from BA hilar LNs and treated with DMF in vitro to observe their differentiation. The effects of DMF were evaluated on BA mouse model, and enzyme-linked immunosorbent assay to measure biochemical markers and cytokine profiles. The Treg/Th17 ratio in the liver was determined by flow cytometry. Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes solute carrier family 7 member 1 (Slc7a11), heme oxygenase - 1 (Hmox1) was validated by q-PCR and Western blot. ScRNA-seq showed CD4<sup>+</sup> T cells in BA liver were enriched in antioxidant pathways. The Treg/Th17 ratio in BA hilar LNs was significantly reduced compared to CC. In vitro, DMF promoted Treg differentiation and inhibited Th17 differentiation. In vivo, the Treg/Th17 ratio increased in the liver of the DMF 40 mg/kg group. In the 40 mg/kg DMF group, interleukin-17 A (IL-17 A) expression decreased as seen in pathological staining. DMF increased Nrf2, Hmox1, Slc7a11 mRNA and protein levels in DMF 40 mg/kg group. There is a Treg/Th17 imbalance in BA patients' hilar LNs, which DMF can restore in vitro. DMF improves the survival rate of BA mice and corrects the Treg/Th17 imbalance, possibly via the Nrf2/antioxidant response elements (ARE) pathway.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110439"},"PeriodicalIF":4.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037510","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}
Zhao-Xing Gao , Yang Fang , Shu-Zhen Xu , Yi-Sheng He , Man Ge , Peng Zhang , Yi-Qing Xu , Tian He , Peng Wang , De-Guang Wang , Hai-Feng Pan
{"title":"Integrated analysis of ATAC-seq and RNA-seq reveals the chromatin accessibility and transcriptional landscape of immunoglobulin a nephropathy","authors":"Zhao-Xing Gao , Yang Fang , Shu-Zhen Xu , Yi-Sheng He , Man Ge , Peng Zhang , Yi-Qing Xu , Tian He , Peng Wang , De-Guang Wang , Hai-Feng Pan","doi":"10.1016/j.clim.2025.110432","DOIUrl":"10.1016/j.clim.2025.110432","url":null,"abstract":"<div><h3>Backgrounds</h3><div>The association between chromatin accessibility in CD4<sup>+</sup> T cells and Immunoglobulin A nephropathy (IgAN) remains unclear.</div></div><div><h3>Methods</h3><div>We performed the assay for transposase accessible chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq) on CD4<sup>+</sup> T cells. ATAC-seq and RNA-seq were conducted to identify differentially accessible regions and differentially expressed genes (DEGs), respectively (<em>P</em> < 0.05, |log2 Fold Change| >1). QRT-PCR was utilized to validate target gene expression.</div></div><div><h3>Results</h3><div>We identified 100,865 differentially accessible regions, of which 7225 exhibited higher accessibility in IgAN. Functional analysis revealed that these regions are enriched in T lymphocyte activation and immune pathways. ELF3, MEIS1, and NFYC were identified as key TFs associated with IgAN. QRT-PCR indicated a significant upregulation of hub genes including MEIS1 in IgAN.</div></div><div><h3>Conclusion</h3><div>We identified key TFs and genes by integrating ATAC-seq and RNA-seq, which provide novel therapeutic targets for IgAN and insights into its pathogenesis from an epigenetic perspective.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110432"},"PeriodicalIF":4.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028087","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}
Yinlan Wu , Yanhong Li , Yu Zhou , Yubin Luo , Lu Cheng , Jing Zhao , Deying Huang , Ling Ma , Tong Wu , Xiuping Liang , Zehui Liao , Chunyu Tan , Yi Liu
{"title":"A nomogram for the prediction of co-infection in MDA5 dermatomyositis: A rapid clinical assessment model","authors":"Yinlan Wu , Yanhong Li , Yu Zhou , Yubin Luo , Lu Cheng , Jing Zhao , Deying Huang , Ling Ma , Tong Wu , Xiuping Liang , Zehui Liao , Chunyu Tan , Yi Liu","doi":"10.1016/j.clim.2025.110431","DOIUrl":"10.1016/j.clim.2025.110431","url":null,"abstract":"<div><h3>Background</h3><div>Patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5 DM) are prone to infections, but there is a lack of rapid methods to assess infection risk, which greatly affects patient prognosis. This study aims to analyze the clinical features of MDA5 DM patients systematically and develop a predictive model for infections.</div></div><div><h3>Methods</h3><div>Retrospective analysis was performed on clinical data from 118 hospitalized patients with MDA5 DM. According to the results of pathogen detection and clinical manifestations, the patients were divided into infected group and non-infected group. LASSO analysis and multivariate logistic regression were used to establish the prediction model of infection in MAD5 DM patients. The resulting model was visualized using a Nomogram. We used methods such as Receiver Operating Characteristic (ROC) curve analysis, Area Under the Curve (AUC) calculation to evaluate the model.</div></div><div><h3>Result</h3><div>The Cough, interstitial lung disease, moist rales, positive anti-RO-52, carcinoembryonic antigen, triglyceride, hydroxybutyrate dehydrogenase and erythrocyte sedimentation rate were significantly associated with infection risk in MDA5 DM patients. A prediction model was developed using these eight risk factors, achieving an AUC of 0.851 in determining co-infection status. Further analysis based on infection site and pathogen classification demonstrated strong discrimination performance of the model in identifying pulmonary infection (AUC: 0.844) and fungal infection (AUC: 0.822).</div></div><div><h3>Conclusion</h3><div>This study aimed to develop a clinical prediction model and visualize it using Nomogram to assess the risk of infection in MDA5 DM. The model provides an effective tool for determining infection status in patients and serves as a reference for formulating clinical medication regimens.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110431"},"PeriodicalIF":4.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022171","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}
Daniel Alvarez-Sierra , Mónica Martínez-Gallo , Adrián Sánchez-Montalvá , Marco Fernández-Sanmartín , Roger Colobran , Juan Espinosa-Pereiro , Elísabet Poyatos-Canton , Coral Zurera-Egea , Alex Sánchez-Pla , Concepción Violan , Rafael Parra , Hammad Alzayat , Ana Vivancos , Francisco Morandeira-Rego , Blanca Urban-Vargas , Eva Martínez-Cáceres , Manuel Hernández-González , Jordi Bas-Minguet , Peter D. Katsikis , Aina Teniente-Serra , Ricardo Pujol-Borrell
{"title":"The immune response to SARS-CoV-2 in COVID-19 as a recall response susceptible to immune imprinting: A prospective cohort study","authors":"Daniel Alvarez-Sierra , Mónica Martínez-Gallo , Adrián Sánchez-Montalvá , Marco Fernández-Sanmartín , Roger Colobran , Juan Espinosa-Pereiro , Elísabet Poyatos-Canton , Coral Zurera-Egea , Alex Sánchez-Pla , Concepción Violan , Rafael Parra , Hammad Alzayat , Ana Vivancos , Francisco Morandeira-Rego , Blanca Urban-Vargas , Eva Martínez-Cáceres , Manuel Hernández-González , Jordi Bas-Minguet , Peter D. Katsikis , Aina Teniente-Serra , Ricardo Pujol-Borrell","doi":"10.1016/j.clim.2025.110429","DOIUrl":"10.1016/j.clim.2025.110429","url":null,"abstract":"<div><div>The antibody response to SARS-CoV-2 does not follow the immunoglobulin isotype pattern of primary responses, conflicting with the current interpretation of COVID-19.</div></div><div><h3>Methods</h3><div>Prospective cohort study of 191 SARS-CoV-2 infection cases and 44 controls from the second wave of COVID-19. The study stratified patients by severity and analyzed the trajectories of SARS-CoV-2 antibodies and multiple immune variables.</div></div><div><h3>Results</h3><div>Isotype-specific antibody time course profiles to SARS-CoV-2 revealed a pattern of recall response in 94.2 % of cases. The time course profiles of plasmablasts, B cells, cTfh high-resolution subsets, and cytokines indicated a secondary response. The transcriptomic data showed that this cohort is strictly comparable to contemporary cohorts.</div></div><div><h3>Conclusions</h3><div>In most cases, the immune response to SARS-CoV-2 is a recall response. This constitutes a favorable scenario for most COVID-19 cases to be subjected to immune imprinting by endemic coronavirus, which, in turn, can influence the immune response to SARS-CoV-2.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"272 ","pages":"Article 110429"},"PeriodicalIF":4.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022239","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}