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Hyper-reactivity of CD8+ T cells and high expression of IL-3 correlates with occurrence and severity of Long-COVID
IF 4.5 3区 医学 Q2 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
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+ 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+ 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+ T cell hyper-activation and hyper-reactivity in Long-COVID and speak for a trial of T cell-immunosuppression in patients with Long-COVID.
{"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
IF 4.5 3区 医学 Q2 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
Heterozygous mutations in the interferon regulatory factor 4 (IRF4) 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 IRF4 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 IRF4 mutations.
{"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
IF 4.5 3区 医学 Q2 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
Hemizygous germline loss-of-function variants in DOCK11, 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 DOCK11, commonly manifesting with autoimmune cytopenias, inflammatory bowel disease, benign lymphoproliferation and systemic inflammation. In this study, we identified a novel variant in DOCK11 (c.3754C > 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.
最近发现,编码细胞分裂 11(DOCK11)的基因 DOCK11 的半合子种系功能缺失变体可导致可变的免疫缺陷和免疫失调。据报道,迄今发现的所有患有 DOCK11 损伤性变异的男性患者都有免疫失调的特征,通常表现为自身免疫性细胞减少症、炎症性肠病、良性淋巴细胞增生和全身性炎症。在这项研究中,我们在一名有复发性肺炎、支气管扩张、感染引发的高炎症和持续性全身炎症病史的患者身上发现了一个新的 DOCK11 变异基因(c.3754C >T,p.(Q1252*)),该基因会导致蛋白质表达缺失。对以前发现的所有患者和本病例的重新评估显示,导致 DOCK11 表达完全丧失并因此丧失功能的变异与自身炎症和复发性肺炎有关,而错义变异则主要与自身抗体相关的自身免疫特征有关。
{"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
IF 4.5 3区 医学 Q2 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
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 (p < 0.05; FC > 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.
{"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
IF 4.5 3区 医学 Q2 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
Gain-of-function variants in stimulator of interferon genes (STING1) 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 STING1 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.
{"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
IF 4.5 3区 医学 Q2 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
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.
{"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
IF 4.5 3区 医学 Q2 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

Background

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.

Objective

To analyze how these autoantibodies influences disease variability in vaccine breakthrough COVID-19 pneumonia patients.

Methods

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.

Results

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 %; p = 0.037). Having these autoantibodies was an independent predictor for critical COVID-19 pneumonia (OR 2.88 [95 %CI 1.18–6.98]).

Conclusion

Vaccination considerably reduces the severity of COVID-19; however, patients with type I interferon autoantibodies remain at increased risk of severe disease.
背景在未接种疫苗的患者中,针对 I 型干扰素的中和自身抗体与严重的 COVID-19 密切相关;然而,这一点尚未在接种疫苗的个体中进行评估。目的分析这些自身抗体如何影响疫苗突破 COVID-19 肺炎患者的疾病变异性。方法收集西班牙贝尔维奇大学医院 2021 年 4 月至 2022 年 12 月期间收治的所有接种过 COVID-19 疫苗的肺炎患者的临床和实验室数据、阻断干扰素-α2 和干扰素-ω的自身抗体以及对 SARS-CoV-2 疫苗的体液反应。中和干扰素的自身抗体在重症肺炎患者中的流行率明显高于轻症肺炎患者(8.8% 对 3.6%;P = 0.037)。结论接种疫苗可大大降低 COVID-19 的严重程度;但是,I 型干扰素自身抗体患者罹患重症的风险仍然会增加。
{"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
IF 4.5 3区 医学 Q2 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

Background

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.

Methods

Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of Streptococcus pneumoniae 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.

Findings

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.

Conclusion

Nasal inoculation with S. pneumoniae 6B induced mild, mucosal inflammation but established carriage was not pro-inflammatory. This suggests that nasal inoculation as a vaccine strategy could be asymptomatic.
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引用次数: 0
An increase in IL-10-producing DNT cells is associated with the pathogenesis of pediatric SLE
IF 4.5 3区 医学 Q2 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
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.
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引用次数: 0
BNT162b2 mRNA vaccination attenuates innate immune function in humans
IF 4.5 3区 医学 Q2 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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引用次数: 0
期刊
Clinical immunology
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