Clinical immunology最新文献

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Hyper-reactivity of CD8+ T cells and high expression of IL-3 correlates with occurrence and severity of Long-COVID CD8+ T细胞的高反应性和IL-3的高表达与Long-COVID的发生和严重程度相关
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-24 DOI: 10.1016/j.clim.2025.110502
Kerstin Renner , Franz Stauffenberg , Moritz Paulus , Sophia Neumayer , Frederike Winter-Köhler , Simone Buchtler , Daniel Schmalenberger , Stefan Blaas , Arno Mohr , Michael Pfeifer , Maximilian V. Malfertheiner , Thomas Loew , Martina Sester , Robert Bals , David Peterhoff , Barbara Schmidt , Matthias Mack
{"title":"Hyper-reactivity of CD8+ T cells and high expression of IL-3 correlates with occurrence and severity of Long-COVID","authors":"Kerstin Renner ,&nbsp;Franz Stauffenberg ,&nbsp;Moritz Paulus ,&nbsp;Sophia Neumayer ,&nbsp;Frederike Winter-Köhler ,&nbsp;Simone Buchtler ,&nbsp;Daniel Schmalenberger ,&nbsp;Stefan Blaas ,&nbsp;Arno Mohr ,&nbsp;Michael Pfeifer ,&nbsp;Maximilian V. Malfertheiner ,&nbsp;Thomas Loew ,&nbsp;Martina Sester ,&nbsp;Robert Bals ,&nbsp;David Peterhoff ,&nbsp;Barbara Schmidt ,&nbsp;Matthias Mack","doi":"10.1016/j.clim.2025.110502","DOIUrl":"10.1016/j.clim.2025.110502","url":null,"abstract":"<div><div>Following SARS-CoV-2 infection, some individuals develop Long-COVID-syndrome lasting for more than 3 months. We analyzed blood samples from patients with Long-COVID, controls without persistent symptoms following SARS-CoV-2-infection and non-infected donors without a history of infection. Long-COVID patients showed clear signs of T cell hyper-activation predominantly in the CD8<sup>+</sup> T cell subset with a 4-fold higher expression of CD25 and 2-fold more effector-memory T cells. Following polyclonal T cell stimulation, we found a 2-fold stronger upregulation of CD25 and a 7-fold higher release of IL-3 in Long-COVID. Intracellular staining revealed 5-fold more IL-3-expressing CD8<sup>+</sup> T cells in Long-COVID, while GM-CSF, IFN-γ and IL-2 were much less upregulated. These changes correlated with the severity of Long-COVID and persisted for up to 18 months after infection. Our data reveal a pronounced and long-lasting CD8<sup>+</sup> T cell hyper-activation and hyper-reactivity in Long-COVID and speak for a trial of T cell-immunosuppression in patients with Long-COVID.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110502"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874769","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
Allogeneic hematopoietic stem cell transplantation in a patient with combined immunodeficiency caused by IRF4 mutation 同种异体造血干细胞移植治疗IRF4突变合并免疫缺陷1例
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-22 DOI: 10.1016/j.clim.2025.110505
Ping Wang , Xiaowen Qian , Wenjin Jiang , Hongsheng Wang , Jinqiao Sun , Xiaochuan Wang , Xiaowen Zhai
{"title":"Allogeneic hematopoietic stem cell transplantation in a patient with combined immunodeficiency caused by IRF4 mutation","authors":"Ping Wang ,&nbsp;Xiaowen Qian ,&nbsp;Wenjin Jiang ,&nbsp;Hongsheng Wang ,&nbsp;Jinqiao Sun ,&nbsp;Xiaochuan Wang ,&nbsp;Xiaowen Zhai","doi":"10.1016/j.clim.2025.110505","DOIUrl":"10.1016/j.clim.2025.110505","url":null,"abstract":"<div><div>Heterozygous mutations in the interferon regulatory factor 4 (<em>IRF4</em>) can lead to combined immunodeficiency in humans. We report a pediatric case involving a male patient who presented with recurrent pneumonia, chronic diarrhoea, abdominal pain, and a skin rash. Laboratory evaluation revealed hypoglobulinemia and persistent B-cell lymphopenia. Genetic analysis confirmed that the combined immunodeficiency was caused by an <em>IRF4</em> mutation. Given the failure of conventional therapies, the patient successfully underwent allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor using a reduced-toxicity conditioning regimen. Post-transplant follow-up demonstrated successful immune reconstitution and complete resolution of gastrointestinal symptoms. This case provides clinical evidence supporting HSCT as a feasible strategy to reconstitute the immune system and resolve enteropathy in patients with <em>IRF4</em> mutations.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110505"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869584","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
A novel hemizygous nonsense variant in DOCK11 causes systemic inflammation and immunodeficiency 一种新的半合子无义DOCK11变异引起全身炎症和免疫缺陷
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-22 DOI: 10.1016/j.clim.2025.110504
Abdulwahab Elsayed , Sandra von Hardenberg , Faranaz Atschekzei , Paul Siek , Torsten Witte , Georgios Sogkas , Felix C. Ringshausen
{"title":"A novel hemizygous nonsense variant in DOCK11 causes systemic inflammation and immunodeficiency","authors":"Abdulwahab Elsayed ,&nbsp;Sandra von Hardenberg ,&nbsp;Faranaz Atschekzei ,&nbsp;Paul Siek ,&nbsp;Torsten Witte ,&nbsp;Georgios Sogkas ,&nbsp;Felix C. Ringshausen","doi":"10.1016/j.clim.2025.110504","DOIUrl":"10.1016/j.clim.2025.110504","url":null,"abstract":"<div><div>Hemizygous germline loss-of-function variants in <em>DOCK11</em>, the gene encoding the dedicator of cytokinesis 11 (DOCK11) have been recently identified to cause variable immunodeficiency and immune dysregulation. Features of immune dysregulation have been reported in all so far identified male patients with damaging variants in <em>DOCK11</em>, commonly manifesting with autoimmune cytopenias, inflammatory bowel disease, benign lymphoproliferation and systemic inflammation. In this study, we identified a novel variant in <em>DOCK11</em> (c.3754C &gt; T, p.(Q1252*)), leading to loss of protein expression, in a patient with a history of recurrent pneumonia, bronchiectasis, infection-triggered hyperinflammation and persistent systemic inflammation. Reevaluation of all previously identified patients and the current case, reveals that variants leading to the complete loss of DOCK11 expression and consequently function rather associate with autoinflammation and recurrent pneumonias, while missense variants, primarily associate with autoantibody-related autoimmune features.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110504"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869585","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
1000-plex antibody array proteomic screen uncovers PGRPS, Haptoglobin, Serpin A4 and Fibrinogen as potential stool biomarkers of pediatric inflammatory bowel disease 1000 plex抗体阵列蛋白质组学筛选发现PGRPS, Haptoglobin, Serpin A4和fibrin原是儿童炎症性肠病的潜在粪便生物标志物
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-17 DOI: 10.1016/j.clim.2025.110495
Ryan Pereira , Sanam Soomro , Kamala Vanarsa , Jessica Castillo , Vinaika Maruvada , Subra Kugathasan , Chandra Mohan
{"title":"1000-plex antibody array proteomic screen uncovers PGRPS, Haptoglobin, Serpin A4 and Fibrinogen as potential stool biomarkers of pediatric inflammatory bowel disease","authors":"Ryan Pereira ,&nbsp;Sanam Soomro ,&nbsp;Kamala Vanarsa ,&nbsp;Jessica Castillo ,&nbsp;Vinaika Maruvada ,&nbsp;Subra Kugathasan ,&nbsp;Chandra Mohan","doi":"10.1016/j.clim.2025.110495","DOIUrl":"10.1016/j.clim.2025.110495","url":null,"abstract":"<div><div>Easy to obtain and in close proximity to the affected areas, fecal samples offer significant potential for the advancement of non-invasive diagnostic methods for inflammatory bowel disease (IBD). A cross-sectional antibody array-based proteomic screen of 1000 fecal protein biomarkers was conducted using stool from treatment naïve control, Crohn's disease (CD), and ulcerative colitis (UC) subjects (control = 24, CD = 39, UC = 10). 71 proteins were significantly elevated in IBD stool (<em>p</em> &lt; 0.05; FC &gt; 2), pointing to cytokine signaling, inflammatory response and extra-cellular matrix functional pathways. Several proteins outperformed fecal calprotectin in distinguishing IBD from control stool, including Haptoglobin, IL-1 R9, GDF-15, PGRPS, Serpin A4, INSRR, SSEA-1, Fibrinogen, IGFBP-1, and TGF-β RI/ALK-5. Upon ELISA validation, PGRPS (AUC = 0.96), Haptoglobin (AUC = 0.91), Serpin A4 (AUC = 0.73), emerged as the most discriminatory biomarkers. Taken together with previous cross-sectional and longitudinal studies, the present findings authenticate stool PGRPS, Haptoglobin, Serpin A4 and fibrinogen as potential stool biomarkers of UC and CD, worthy of further prospective studies to identify more reliable and accurate non-invasive biomarkers for IBD.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110495"},"PeriodicalIF":4.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869586","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
A novel STING1-activating mutation is identified in a patient with childhood-onset systemic lupus erythematosus 一种新的sting - 1激活突变在儿童发病的系统性红斑狼疮患者中被发现
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-11 DOI: 10.1016/j.clim.2025.110493
Ting Li , Siming Peng , Yu Zhou, Caihui Zhang, Gexuan Feng, Zhongxun Yu, Yiwen Xu, Meiying Quan, Wei Wang , Hongmei Song
{"title":"A novel STING1-activating mutation is identified in a patient with childhood-onset systemic lupus erythematosus","authors":"Ting Li ,&nbsp;Siming Peng ,&nbsp;Yu Zhou,&nbsp;Caihui Zhang,&nbsp;Gexuan Feng,&nbsp;Zhongxun Yu,&nbsp;Yiwen Xu,&nbsp;Meiying Quan,&nbsp;Wei Wang ,&nbsp;Hongmei Song","doi":"10.1016/j.clim.2025.110493","DOIUrl":"10.1016/j.clim.2025.110493","url":null,"abstract":"<div><div>Gain-of-function variants in stimulator of interferon genes (<em>STING1</em>) are known to cause STING-associated vasculopathy with onset in infancy (SAVI), a disorder characterized by cutaneous vasculopathy, interstitial lung disease (ILD), and systemic inflammation. Here, we report a novel <em>STING1</em> N188H variant in a patient who met the classification criteria for systemic lupus erythematosus (SLE) but lacked typical SAVI features. In vitro assays demonstrated that the N188H variant drives constitutive STING activation and enhances type I interferon signaling. Consistent with this, the patient exhibited elevated interferon-stimulated genes (ISGs) expression, and RNA sequencing confirmed significant upregulation of type I IFN signaling compared to healthy controls. Our findings expand the molecular spectrum of STING-associated disease.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110493"},"PeriodicalIF":4.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825441","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
Neutralizing antibody responses after a two-dose regimen with BNT162b2, CoronaVac or ChAdOx1-S in Brazil: Differential neutralization of SARS-CoV-2 omicron variants 在巴西,BNT162b2、CoronaVac或ChAdOx1-S两剂量方案后的中和抗体反应:SARS-CoV-2组粒变体的差异中和
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-02 DOI: 10.1016/j.clim.2025.110492
Isabela Pazotti Daher , Bianca da Silva Almeida , Guilherme Antonio de Souza-Silva , Rodolfo Ferreira Marques , Gustavo Henrique Corrêa Soares , Robert Andreata-Santos , Ana Moretti , Mariângela de Oliveira Silva , Viviane Schuch , Greyce Luri Sasahara , Andréia Kuramoto , Marcio Yamamoto , Luís Carlos de Souza Ferreira , Keity Santos , Verônica P.C.V. Coelho , Jorge Kalil , Daniela Santoro Rosa , Edecio Cunha-Neto , Silvia Beatriz Boscardin
{"title":"Neutralizing antibody responses after a two-dose regimen with BNT162b2, CoronaVac or ChAdOx1-S in Brazil: Differential neutralization of SARS-CoV-2 omicron variants","authors":"Isabela Pazotti Daher ,&nbsp;Bianca da Silva Almeida ,&nbsp;Guilherme Antonio de Souza-Silva ,&nbsp;Rodolfo Ferreira Marques ,&nbsp;Gustavo Henrique Corrêa Soares ,&nbsp;Robert Andreata-Santos ,&nbsp;Ana Moretti ,&nbsp;Mariângela de Oliveira Silva ,&nbsp;Viviane Schuch ,&nbsp;Greyce Luri Sasahara ,&nbsp;Andréia Kuramoto ,&nbsp;Marcio Yamamoto ,&nbsp;Luís Carlos de Souza Ferreira ,&nbsp;Keity Santos ,&nbsp;Verônica P.C.V. Coelho ,&nbsp;Jorge Kalil ,&nbsp;Daniela Santoro Rosa ,&nbsp;Edecio Cunha-Neto ,&nbsp;Silvia Beatriz Boscardin","doi":"10.1016/j.clim.2025.110492","DOIUrl":"10.1016/j.clim.2025.110492","url":null,"abstract":"<div><div>The emergence of SARS-CoV-2 variants has reduced antibody effectiveness, affecting vaccine protection. This study evaluated neutralizing antibodies against Wuhan strain and several variants, including Alpha, Beta, Gamma, Delta, and Omicron, in Brazilians vaccinated twice with CoronaVac, ChAdOx1-S, or BNT162b2 before Delta and Omicron emerged. After the booster, strong antibody responses to the Wuhan strain were seen in all groups, but BNT162b2 resulted in higher anti-Spike and anti-RBD IgG levels. While all vaccines showed some cross-neutralization against Alpha, Beta, Gamma, and Delta, only BNT162b2 was effective against Omicron BA.2 and BA.4/5 subvariants. Furthermore, BNT162b2 vaccination showed a positive correlation between Wuhan RBD-specific IgG and Omicron neutralizing antibodies. This group demonstrated distinct clustering patterns of neutralizing antibodies against all variants, unlike those from CoronaVac and ChAdOx1-S. The findings suggest BNT162b2 offers broader neutralization capability, highlighting the benefit of booster shots with bivalent mRNA vaccines to enhance immune responses against emerging variants.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110492"},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788030","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
Autoantibodies neutralizing type I interferons remain a significant risk factor for critical COVID-19 pneumonia in vaccinated patients 中和I型干扰素的自身抗体仍然是接种疫苗患者发生COVID-19重症肺炎的重要危险因素
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-02 DOI: 10.1016/j.clim.2025.110491
Arnau Antolí , José Luis Gómez-Vázquez , Angels Sierra-Fortuny , Carla Bermudez-Carre , Mario Framil , Edgar Creus-Bachiller , Julen Viana-Errasti , Paula Rofes , Gemma Rocamora-Blanch , Lara Hidalgo-Peña , Lydia García-Serrano , Raúl Rigo-Bonnin , Lidia Feliubadaló , Jesús del Valle , Laura Calatayud , Francisco Morandeira , Conxi Lázaro , Xavier Solanich
{"title":"Autoantibodies neutralizing type I interferons remain a significant risk factor for critical COVID-19 pneumonia in vaccinated patients","authors":"Arnau Antolí ,&nbsp;José Luis Gómez-Vázquez ,&nbsp;Angels Sierra-Fortuny ,&nbsp;Carla Bermudez-Carre ,&nbsp;Mario Framil ,&nbsp;Edgar Creus-Bachiller ,&nbsp;Julen Viana-Errasti ,&nbsp;Paula Rofes ,&nbsp;Gemma Rocamora-Blanch ,&nbsp;Lara Hidalgo-Peña ,&nbsp;Lydia García-Serrano ,&nbsp;Raúl Rigo-Bonnin ,&nbsp;Lidia Feliubadaló ,&nbsp;Jesús del Valle ,&nbsp;Laura Calatayud ,&nbsp;Francisco Morandeira ,&nbsp;Conxi Lázaro ,&nbsp;Xavier Solanich","doi":"10.1016/j.clim.2025.110491","DOIUrl":"10.1016/j.clim.2025.110491","url":null,"abstract":"<div><h3>Background</h3><div>Neutralizing autoantibodies against type I interferons were strongly linked to severe COVID-19 in unvaccinated patients; however, this has yet to be evaluated in vaccinated individuals.</div></div><div><h3>Objective</h3><div>To analyze how these autoantibodies influences disease variability in vaccine breakthrough COVID-19 pneumonia patients.</div></div><div><h3>Methods</h3><div>Clinical and laboratory data; autoantibodies blocking interferon-α2 and –ω; and humoral response to SARS-CoV-2 vaccine were collected from all vaccinated COVID-19 pneumonia patients admitted from April 2021 to December 2022 at Bellvitge University Hospital, Spain.</div></div><div><h3>Results</h3><div>458 patients developed COVID-19 pneumonia despite an appropriate antibody response to SARS-CoV-2 vaccination. Autoantibodies neutralizing interferons were significantly more prevalent in patients with critical pneumonia compared to those with milder forms (8.8 % vs. 3.6 %; <em>p</em> = 0.037). Having these autoantibodies was an independent predictor for critical COVID-19 pneumonia (OR 2.88 [95 %CI 1.18–6.98]).</div></div><div><h3>Conclusion</h3><div>Vaccination considerably reduces the severity of COVID-19; however, patients with type I interferon autoantibodies remain at increased risk of severe disease.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110491"},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769018","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
Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage 在一项使用实验性人肺炎球菌携带的随机疫苗试验中,粘膜中性粒细胞炎症和细胞因子反应与自然和实验性肺炎球菌携带的关联
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-04-01 DOI: 10.1016/j.clim.2025.110489
Gift Chiwala , Raphael Kamng'ona , Evaristar Kudowa , Godwin Tembo , Mphatso Mayuni , Lorensio Chimgoneko , Morrison Kamanga , Faith Thole , Tiyamike Nthandira , Bridgette Galafa , Glory Kadzanja , Tarsizio Chikaonda , John Ndaferankhande , Anthony Chirwa , Edna Nsomba , Lumbani Makhaza , Innocent Sulani , Alfred Muyaya , Neema Toto , Marc Y.R. Henrion , Stephen B. Gordon
{"title":"Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage","authors":"Gift Chiwala ,&nbsp;Raphael Kamng'ona ,&nbsp;Evaristar Kudowa ,&nbsp;Godwin Tembo ,&nbsp;Mphatso Mayuni ,&nbsp;Lorensio Chimgoneko ,&nbsp;Morrison Kamanga ,&nbsp;Faith Thole ,&nbsp;Tiyamike Nthandira ,&nbsp;Bridgette Galafa ,&nbsp;Glory Kadzanja ,&nbsp;Tarsizio Chikaonda ,&nbsp;John Ndaferankhande ,&nbsp;Anthony Chirwa ,&nbsp;Edna Nsomba ,&nbsp;Lumbani Makhaza ,&nbsp;Innocent Sulani ,&nbsp;Alfred Muyaya ,&nbsp;Neema Toto ,&nbsp;Marc Y.R. Henrion ,&nbsp;Stephen B. Gordon","doi":"10.1016/j.clim.2025.110489","DOIUrl":"10.1016/j.clim.2025.110489","url":null,"abstract":"<div><h3>Background</h3><div>Mucosal inflammation is associated with increased nasal pneumococcal colonisation, but the specific mechanisms are not fully understood. We aimed to find innate immune factors associated with pneumococcal carriage using a controlled human infection model.</div></div><div><h3>Methods</h3><div>Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of <em>Streptococcus pneumoniae</em> 6B. We categorised the participants into 4 pneumococcal carriage outcome groups - no carriage; natural carriage; experimental carriage; and dual carriage. We then measured neutrophil to lymphocyte ratio (NLR) in nasal mucosa and cytokine levels in nasal lining fluid at 7 days before and 2, 7 and 14 days after inoculation.</div></div><div><h3>Findings</h3><div>We found that 45 % of participants had no carriage, 35 % had natural carriage, 12 % experimental carriage and 8 % dual carriage. At 2- and 7-days post inoculation, all groups showed an increase in NLR compared to 7 days before inoculation, accompanied by small changes in cytokine levels. An early increase in NLR was associated with protection against experimental carriage while cytokines did not associate with carriage pattern.</div></div><div><h3>Conclusion</h3><div>Nasal inoculation with <em>S. pneumoniae</em> 6B induced mild, mucosal inflammation but established carriage was not pro-inflammatory. This suggests that nasal inoculation as a vaccine strategy could be asymptomatic.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110489"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779295","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
An increase in IL-10-producing DNT cells is associated with the pathogenesis of pediatric SLE 产生il -10的DNT细胞的增加与儿童SLE的发病机制有关
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-03-28 DOI: 10.1016/j.clim.2025.110490
Qixin Wang , Shipeng Li , Yannan Wei , Chen Xu , Xiangjun Liu , Xiaolin Wang , Wenjia Chai , Wenjun Mou , Xi Chen , Caifeng Li , Caisheng Wang , Jingang Gui
{"title":"An increase in IL-10-producing DNT cells is associated with the pathogenesis of pediatric SLE","authors":"Qixin Wang ,&nbsp;Shipeng Li ,&nbsp;Yannan Wei ,&nbsp;Chen Xu ,&nbsp;Xiangjun Liu ,&nbsp;Xiaolin Wang ,&nbsp;Wenjia Chai ,&nbsp;Wenjun Mou ,&nbsp;Xi Chen ,&nbsp;Caifeng Li ,&nbsp;Caisheng Wang ,&nbsp;Jingang Gui","doi":"10.1016/j.clim.2025.110490","DOIUrl":"10.1016/j.clim.2025.110490","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that causes immune system overactivity and organ damage. Among T-cell subsets involved in SLE, CD4 and CD8 double-negative αβT (DNT) cells have attracted attention in recent years, although their role in SLE remains poorly understood. Examining the minute intricacies, particularly signaling pathway modifications is crucial, as it may unveil potential therapeutic targets and lead to the development of more effective treatments. Our study found increased DNT cells in pediatric SLE patients, with elevated IL-10 signaling. These IL-10-producing DNT cells were positively related to disease activity defined by SLE Disease Activity Index (SLEDAI), and were further elevated in patients with lupus nephritis. Additionally, our results indicated that IL-10-producing DNT cells correlated positively with anti-Sm autoantibodies. Collectively, our study revealed that modulation of IL-10 production within DNT-cell subset could affect both immune regulation and autoantibody production, contributing to the immunological dysregulation in SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110490"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747263","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
BNT162b2 mRNA vaccination attenuates innate immune function in humans 接种BNT162b2 mRNA可减弱人的先天免疫功能。
IF 4.5 3区 医学
Clinical immunology Pub Date : 2025-03-25 DOI: 10.1016/j.clim.2025.110488
Sarah A. Connolly , Aaron Walsh , Anna E. Ledwith , Karen N. McCarthy , Sinead A. O’Rourke , Dearbhla M. Murphy , Anna Blasinska , Aisling Dunne , Jean M. Fletcher , Kingston H.G. Mills , Ross McManus , Frederick J. Sheedy , Sharee A. Basdeo
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