Pub Date : 2025-01-20DOI: 10.1016/j.clim.2025.110429
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
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.
Methods
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.
Results
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.
Conclusions
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.
{"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}
Pub Date : 2024-11-28DOI: 10.1016/j.clim.2024.110412
Cheng Ju , Renfeng Liu , Yanming Ma , Hui Dong , Ruiqing Xu , Huimin Hu , Dingjun Hao
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.
{"title":"Single-cell analysis combined with transcriptome sequencing identifies autophagy hub genes in macrophages after spinal cord injury","authors":"Cheng Ju , Renfeng Liu , Yanming Ma , Hui Dong , Ruiqing Xu , Huimin Hu , 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}
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.
腺苷脱氨酶（ADA）缺乏症通常在婴儿早期表现为严重的联合免疫缺陷，但在某些病例中可能会延迟发病。我们遇到了两名成年后才被诊断出患有 ADA 缺乏症的患者。除了以前报道过的病例外，我们还旨在确定和描述与迟发和晚发 ADA 缺乏症相关的临床和免疫学特征。这两名患者均在幼年时期出现肺炎和甲状腺功能减退症。患者随后接受了定期补充免疫球蛋白和左甲状腺素治疗。他们反复感染，包括肺炎和带状疱疹，成年后被诊断为 ADA 缺乏症。文献综述显示，10 岁以后确诊的患者从发病到确诊的中位时间间隔为 18 年。合并免疫缺陷和反复下呼吸道感染或自身免疫性疾病的患者需要尽早测量 ADA 活性或进行基因分析。
{"title":"Prolonged diagnostic journey in delayed-onset adenosine deaminase deficiency","authors":"Dan Tomomasa , Masatoshi Takagi , Ryohei Watanabe , Ryosuke Wakatsuki , Satoshi Miyamoto , Akihiro Hoshino , Takahiro Kamiya , Takeshi Isoda , Anju Kobayashi , Kenjiro Kosaki , Fumiaki Sakura , Takaki Asano , Toru Uchiyama , Satoshi Okada , Tomohiro Morio , 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}
Pub Date : 2024-11-23DOI: 10.1016/j.clim.2024.110403
Hilal Ünsal , Ahsen Ekinci , Gülnar Aliyeva , Hacer Neslihan Bildik , Saliha Esenboğa , Deniz Çağdaş
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) (n = 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.
{"title":"Characteristics of patients with low serum IgE levels and selective IgE deficiency: Data from an immunodeficiency referral center","authors":"Hilal Ünsal , Ahsen Ekinci , Gülnar Aliyeva , Hacer Neslihan Bildik , Saliha Esenboğa , 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}
Pub Date : 2024-11-22DOI: 10.1016/j.clim.2024.110397
Lele Liu , Yuanjun Deng , Qian Li , Yang Cai , Chunjiang Zhang , Tianjing Zhang , Gang Xu , Min Han
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.
{"title":"Sympathetic nerve promotes renal fibrosis by activating M2 macrophages through β2-AR-Gsa","authors":"Lele Liu , Yuanjun Deng , Qian Li , Yang Cai , Chunjiang Zhang , Tianjing Zhang , Gang Xu , 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}
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.
多发性硬化症（MS）是中枢神经系统（CNS）的一种慢性、多因素、炎症性和脱髓鞘疾病，涉及针对髓鞘成分的自身免疫反应。事实证明，抗 B 细胞疗法可成功减少复发。因此，研究疾病两个阶段（复发和缓解）的 B 细胞具有重要意义。在这里，我们利用新一代测序技术分析了复发期和缓解期的 11 名多发性硬化症患者、6 名其他炎症性神经疾病（OIND）患者和 10 名健康受试者（HCs）的外周血细胞 BCR 重排。此外，还采用酶联免疫吸附法对患者和对照组血清中的免疫球蛋白 G、M、A 和 D 进行了定量检测。与其他研究组相比，复发性多发性硬化症患者的 BCR 基因库显示出较低的多样性和较高的体细胞高突变率。在该组中，共享克隆型的比例最高。IGHV4-32基因被确定为MS和OIND之间的潜在差异生物标志物，IGL3-21基因也被确定为MS的潜在生物标志物。另一方面，缓解期 MS 患者血清中 IgG 和 IgD 升高，复发期 MS 患者血清 IgG 也升高。总之，这些结果显示了 B 细胞在多发性硬化症复发的发病机制中的重要作用，并为分析外周血 BCR 重排以获得多发性硬化症诊断工具提供了新的全景图。此外，这项工作还强调了在不同人群中进行研究的必要性，因为由于遗传背景和环境暴露的差异，在高加索人群中报告的结果可能与其他纬度多发性硬化症患者的免疫过程不一致。
{"title":"Comparative analysis of the B cell receptor repertoire during relapse and remission in patients with multiple sclerosis","authors":"Miriam Pérez-Saldívar , Yusuke Nakamura , Kazuma Kiyotani , Seiya Imoto , Kotoe Katayama , Rui Yamaguchi , Satoru Miyano , Jesús Martínez-Barnetche , Elizabeth Ernestina Godoy-Lozano , Graciela Ordoñez , Julio Sotelo , Hugo González-Conchillos , Adolfo Martínez-Palomo , José Flores-Rivera , Leopoldo Santos-Argumedo , Erick Saúl Sánchez-Salguero , 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}
Two major antigen processing pathways represent protein Ags through major histocompatibility complexes (MHC class I and II) or lipid Ags through CD1 molecules influence the tumor immune response. Invariant Natural Killer T cells (iNKT) manage a significant role in cancer immunotherapy. CD1d, found on antigen-presenting cells (APCs), presents lipid Ags to iNKT cells. In many cancers, the number and function of iNKT cell are compromised, leading to immune evasion. Additionally impaired motility of iNKT cells may contribute to poor tumor prognosis. Emerging evidences suggest that CD1d, itself also influences cancer progression. Patient databases further highlight the importance of CD1d expression in different cancers and its correlation with patient survival outcomes. The ability of iNKT cells to activate and enhance the immune response renders them an attractive target for cancer immunotherapy. This review discusses all the possible ways of cancer immune evasion and restoration of immune responses mediated by CD1d-iNKT interactions.
两种主要的抗原处理途径，即通过主要组织相容性复合物（MHC I 类和 II 类）处理蛋白抗原，或通过 CD1 分子处理脂质抗原，对肿瘤免疫反应产生影响。不变自然杀伤 T 细胞（iNKT）在癌症免疫疗法中发挥着重要作用。抗原递呈细胞（APC）上的 CD1d 向 iNKT 细胞递呈脂质抗原。在许多癌症中，iNKT 细胞的数量和功能都会受到损害，从而导致免疫逃避。此外，iNKT 细胞的运动能力受损也可能导致肿瘤预后不良。新的证据表明，CD1d 本身也会影响癌症的进展。患者数据库进一步凸显了 CD1d 在不同癌症中表达的重要性及其与患者生存结果的相关性。iNKT 细胞具有激活和增强免疫反应的能力，使其成为癌症免疫疗法的诱人靶点。本综述讨论了 CD1d-iNKT 相互作用介导的癌症免疫逃避和免疫反应恢复的所有可能途径。
{"title":"Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells","authors":"Ritis Kumar Shyanti , Mazharul Haque , Rajesh Singh , Manoj Mishra","doi":"10.1016/j.clim.2024.110402","DOIUrl":"10.1016/j.clim.2024.110402","url":null,"abstract":"<div><div>Two major antigen processing pathways represent protein Ags through major histocompatibility complexes (MHC class I and II) or lipid Ags through CD1 molecules influence the tumor immune response. Invariant Natural Killer T cells (iNKT) manage a significant role in cancer immunotherapy. CD1d, found on antigen-presenting cells (APCs), presents lipid Ags to iNKT cells. In many cancers, the number and function of iNKT cell are compromised, leading to immune evasion. Additionally impaired motility of iNKT cells may contribute to poor tumor prognosis. Emerging evidences suggest that CD1d, itself also influences cancer progression. Patient databases further highlight the importance of CD1d expression in different cancers and its correlation with patient survival outcomes. The ability of iNKT cells to activate and enhance the immune response renders them an attractive target for cancer immunotherapy. This review discusses all the possible ways of cancer immune evasion and restoration of immune responses mediated by CD1d-iNKT interactions.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"269 ","pages":"Article 110402"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674987","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}
Pub Date : 2024-11-17DOI: 10.1016/j.clim.2024.110399
Alessandra Mazzola , Clémentine Roger , Romain Lhotte , Maxime Mallet , Dominique Thabut , Jean-Luc Taupin , Filomena Conti
Bacterial infections are common in cirrhosis patients, increasing the risk of decompensation and death. The impact of HLA evolutionary divergence (HED) on infection risk hasn't been studied in humans before. We conducted a retrospective study on cirrhosis patients awaiting liver transplantation (LT) from January 2019 to February 2022, examining class I and II-HED effects on bacterial infections and cirrhosis decompensation.
We included 269 cirrhosis patients. Among them, 98 experienced 153 bacterial infections. Multivariable analysis after variable selection revealed that higher class II-HED was linked to fewer bacterial infections (p = 0.034), while class I-HED showed no effect (p = 0.074). Independent risk factors for bacterial infections included invasive procedures (p < 0.001), ICU hospitalization (p < 0.001), recent antibiotic treatment (p = 0.046), rifaximin use (p = 0.043), and cirrhosis decompensation (p = 0.002). Neither class I nor II-HED affected decompensation risk.
This pioneering study shows that high class II-HED levels may protect against bacterial infections in cirrhosis patients awaiting LT, suggesting an immunological mechanism at play.
{"title":"HLA evolutionary divergence effect on bacterial infection risk in cirrhotic liver transplant candidates","authors":"Alessandra Mazzola , Clémentine Roger , Romain Lhotte , Maxime Mallet , Dominique Thabut , Jean-Luc Taupin , Filomena Conti","doi":"10.1016/j.clim.2024.110399","DOIUrl":"10.1016/j.clim.2024.110399","url":null,"abstract":"<div><div>Bacterial infections are common in cirrhosis patients, increasing the risk of decompensation and death. The impact of HLA evolutionary divergence (HED) on infection risk hasn't been studied in humans before. We conducted a retrospective study on cirrhosis patients awaiting liver transplantation (LT) from January 2019 to February 2022, examining class I and II-HED effects on bacterial infections and cirrhosis decompensation.</div><div>We included 269 cirrhosis patients. Among them, 98 experienced 153 bacterial infections. Multivariable analysis after variable selection revealed that higher class II-HED was linked to fewer bacterial infections (<em>p</em> = 0.034), while class I-HED showed no effect (<em>p</em> = 0.074). Independent risk factors for bacterial infections included invasive procedures (<em>p</em> < 0.001), ICU hospitalization (p < 0.001), recent antibiotic treatment (<em>p</em> = 0.046), rifaximin use (<em>p</em> = 0.043), and cirrhosis decompensation (<em>p</em> = 0.002). Neither class I nor II-HED affected decompensation risk.</div><div>This pioneering study shows that high class II-HED levels may protect against bacterial infections in cirrhosis patients awaiting LT, suggesting an immunological mechanism at play.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110399"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674736","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}
Pub Date : 2024-11-17DOI: 10.1016/j.clim.2024.110401
Ashley Sang Eun Lee , Jin Feng , Alp Kazancioglu , Charlotte Cunningham-Rundles
{"title":"Clinical characterization of NOD2 variants in patients with common variable immunodeficiency","authors":"Ashley Sang Eun Lee , Jin Feng , Alp Kazancioglu , Charlotte Cunningham-Rundles","doi":"10.1016/j.clim.2024.110401","DOIUrl":"10.1016/j.clim.2024.110401","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"270 ","pages":"Article 110401"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674732","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}
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