Pub Date : 2025-04-02DOI: 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 , 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","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}
Pub Date : 2025-04-02DOI: 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.
{"title":"Autoantibodies neutralizing type I interferons remain a significant risk factor for critical COVID-19 pneumonia in vaccinated patients","authors":"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","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}
Pub Date : 2025-04-01DOI: 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.
{"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 , 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","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}
Pub Date : 2025-03-28DOI: 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.
{"title":"An increase in IL-10-producing DNT cells is associated with the pathogenesis of pediatric SLE","authors":"Qixin Wang , Shipeng Li , Yannan Wei , Chen Xu , Xiangjun Liu , Xiaolin Wang , Wenjia Chai , Wenjun Mou , Xi Chen , Caifeng Li , Caisheng Wang , 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}
Pub Date : 2025-03-25DOI: 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
{"title":"BNT162b2 mRNA vaccination attenuates innate immune function in humans","authors":"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","doi":"10.1016/j.clim.2025.110488","DOIUrl":"10.1016/j.clim.2025.110488","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110488"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728920","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}
Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the presence of circulating autoantibodies. Autoantibodies targeting C1 complex proteins, particularly C1q, have already been described in lupus nephritis (LN). However, autoantibodies targeting the C1s protease remain poorly studied. We determined the prevalence of anti-C1s autoantibodies in serum of SLE patients, and evaluated their presence in relation to clinical conditions. For this purpose, sera from 187 SLE patients with different disease activity were selected and anti-C1s autoantibodies were measured by ELISA. We observed that patients with LN had significantly higher levels of anti-C1s autoantibodies than SLE patients with other flare types. Anti-C1s autoantibodies recognised mainly the C1s N-terminal part. Interestingly, the combination of anti-C1s, anti-DNA and anti-C1q autoantibodies showed high specificity (94.6 %) and a significant positive predictive value of 80 %. These results suggest the potential interest of anti-C1s autoantibodies as a complementary serological biomarker in the early screening for LN.
{"title":"Anti-C1s autoantibodies as complementary serologic biomarker in lupus nephritis","authors":"Jeanne Vigne , Nolwenn Haut , Giovanna Clavarino , Noémie Jourde-Chiche , Françoise Sarrot-Reynauld , Leendert A. Trouw , Federica Defendi , Nicole M. Thielens , Christine Gaboriaud , Véronique Rossi , Chantal Dumestre-Pérard","doi":"10.1016/j.clim.2025.110487","DOIUrl":"10.1016/j.clim.2025.110487","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the presence of circulating autoantibodies. Autoantibodies targeting C1 complex proteins, particularly C1q, have already been described in lupus nephritis (LN). However, autoantibodies targeting the C1s protease remain poorly studied. We determined the prevalence of anti-C1s autoantibodies in serum of SLE patients, and evaluated their presence in relation to clinical conditions. For this purpose, sera from 187 SLE patients with different disease activity were selected and anti-C1s autoantibodies were measured by ELISA. We observed that patients with LN had significantly higher levels of anti-C1s autoantibodies than SLE patients with other flare types. Anti-C1s autoantibodies recognised mainly the C1s N-terminal part. Interestingly, the combination of anti-C1s, anti-DNA and anti-C1q autoantibodies showed high specificity (94.6 %) and a significant positive predictive value of 80 %. These results suggest the potential interest of anti-C1s autoantibodies as a complementary serological biomarker in the early screening for LN.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110487"},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708916","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 : 2025-03-20DOI: 10.1016/j.clim.2025.110486
Weiqi Zhang , Dejun Kong , Xiaohan Zhang , Lu Hu , Yeqi Nian , Zhongyang Shen
T cell senescence and exhaustion represent critical aspects of adaptive immune system dysfunction, with profound implications for health and the development of disease prevention and therapeutic strategies. These processes, though distinct, are interconnected at the molecular level, leading to impaired effector functions and reduced proliferative capacity of T cells. Such impairments increase susceptibility to diseases and diminish the efficacy of vaccines and treatments. Importantly, T cell senescence and exhaustion can dynamically influence each other, particularly in the context of chronic diseases. A deeper understanding of the molecular mechanisms underlying T cell senescence and exhaustion, as well as their interplay, is essential for elucidating the pathogenesis of related diseases and restoring dysfunctional immune responses. This knowledge will pave the way for the development of targeted therapeutic interventions and strategies to enhance immune competence. This review aims to summarize the characteristics, mechanisms, and disease associations of T cell senescence and exhaustion, while also delineating the distinctions and intersections between these two states to enhance our comprehension.
{"title":"T cell aging and exhaustion: Mechanisms and clinical implications","authors":"Weiqi Zhang , Dejun Kong , Xiaohan Zhang , Lu Hu , Yeqi Nian , Zhongyang Shen","doi":"10.1016/j.clim.2025.110486","DOIUrl":"10.1016/j.clim.2025.110486","url":null,"abstract":"<div><div>T cell senescence and exhaustion represent critical aspects of adaptive immune system dysfunction, with profound implications for health and the development of disease prevention and therapeutic strategies. These processes, though distinct, are interconnected at the molecular level, leading to impaired effector functions and reduced proliferative capacity of T cells. Such impairments increase susceptibility to diseases and diminish the efficacy of vaccines and treatments. Importantly, T cell senescence and exhaustion can dynamically influence each other, particularly in the context of chronic diseases. A deeper understanding of the molecular mechanisms underlying T cell senescence and exhaustion, as well as their interplay, is essential for elucidating the pathogenesis of related diseases and restoring dysfunctional immune responses. This knowledge will pave the way for the development of targeted therapeutic interventions and strategies to enhance immune competence. This review aims to summarize the characteristics, mechanisms, and disease associations of T cell senescence and exhaustion, while also delineating the distinctions and intersections between these two states to enhance our comprehension.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110486"},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691188","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 : 2025-03-19DOI: 10.1016/j.clim.2025.110476
Nora Euler , Erik Hellbacher , Erik af Klint , Monika Hansson , Anders Larsson , Gunilla Enblad , Vivianne Malmström , Eva Baecklund , Caroline Grönwall , the AUTO-LYMPHOMA study group
Patients with rheumatoid arthritis (RA) are at increased risk of diffuse large B cell lymphoma (DLBCL) compared to the general population. Here, we explored the inflammatory profiles in the blood of RA patients who had developed DLBCL. RA-DLBCL patients had significantly higher levels of the pro-inflammatory markers TNF, IL-8, CXCL9, APRIL, and particularly CXCL13 (median 796 vs. 206 pg/mL, p = 0.001), compared to RA controls. By including an extensive autoantibody panel of rheumatoid factor, IgG anti-CCP2, anti-citrullinated protein antibodies (ACPA) fine-specificities, and other anti-modified protein antibodies, all RA-DLBCL patients were autoantibody seropositive. Yet, RA-DLBCL patients did not display significantly different autoantibody signatures compared to RA controls. The levels of immunoglobulin free light chains and C-reactive protein were similar in RA-DLBCL patients and RA controls. In conclusion, RA-DLBCL patients exhibit pro-inflammatory signatures with elevated markers that are important for B cells and may contribute to enhanced B-cell activation and promote lymphoma development.
{"title":"Diffuse large B cell lymphoma in rheumatoid arthritis patients is associated with elevated B-cell driving factors including CXCL13","authors":"Nora Euler , Erik Hellbacher , Erik af Klint , Monika Hansson , Anders Larsson , Gunilla Enblad , Vivianne Malmström , Eva Baecklund , Caroline Grönwall , the AUTO-LYMPHOMA study group","doi":"10.1016/j.clim.2025.110476","DOIUrl":"10.1016/j.clim.2025.110476","url":null,"abstract":"<div><div>Patients with rheumatoid arthritis (RA) are at increased risk of diffuse large B cell lymphoma (DLBCL) compared to the general population. Here, we explored the inflammatory profiles in the blood of RA patients who had developed DLBCL. RA-DLBCL patients had significantly higher levels of the pro-inflammatory markers TNF, IL-8, CXCL9, APRIL, and particularly CXCL13 (median 796 vs. 206 pg/mL, <em>p</em> = 0.001), compared to RA controls. By including an extensive autoantibody panel of rheumatoid factor, IgG anti-CCP2, anti-citrullinated protein antibodies (ACPA) fine-specificities, and other anti-modified protein antibodies, all RA-DLBCL patients were autoantibody seropositive. Yet, RA-DLBCL patients did not display significantly different autoantibody signatures compared to RA controls. The levels of immunoglobulin free light chains and C-reactive protein were similar in RA-DLBCL patients and RA controls. In conclusion, RA-DLBCL patients exhibit pro-inflammatory signatures with elevated markers that are important for B cells and may contribute to enhanced B-cell activation and promote lymphoma development.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110476"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673291","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 : 2025-03-19DOI: 10.1016/j.clim.2025.110474
Langui Tang , Juan Liang , Yazhou Huang , Kaiyun Guo , Yanzhao Huang , Yuxing He , Jun Wang , Ming Lei
Background
The aim of this study was to systematically assess the relationship between Chitinase 3-like protein-1 (CHI3L1) protein and disease progression in multiple myeloma (MM) and to explore its potential clinical value as a biomarker to provide a basis for optimizing treatment strategies.
Methods
136 patients with MM were divided into two groups according to the efficacy: group 1–95 patients with non-progressing MM; group 2–41 patients with progressing MM. The concentration of CHI3L1 in the serum of the patients was determined by enzyme-linked immunosorbent assay (ELISA).
Results
CHI3L1 concentration in patients' serum was significantly greater than in healthy controls (P < 0.001), which patients with International Staging System (ISS) III had significantly higher CHI3L1 concentration than those with stage I/II. Patients in the progressed group had significantly higher CHI3L1 concentration than those in the non-progressed group by comparative analyses. Otherwise, multifactorial logistic regression analyses showed that CHI3L1 concentration was an independent predictor of MM progression after other confounding factors were excluded, and that the risk of progression in the high-concentration group was increased by 243.6 %, relative to the low-concentration group. Moreover, smoothed curve fitting analysis further confirmed that serum CHI3L1 concentration was linearly related to the probability of progression in MM patients, and the risk of progression increased as CHI3L1 concentration increased.
Conclusions
This study indicated that CHI3L1 concentration in the serum of MM patients was closely correlated with disease severity. High concentration CHI3L1 predicted the progression of MM disease, suggesting its clinical application potential in predicting disease prognosis.
{"title":"An analysis of the clinical value of CHI3L1 as a biomarker of multiple myeloma progression","authors":"Langui Tang , Juan Liang , Yazhou Huang , Kaiyun Guo , Yanzhao Huang , Yuxing He , Jun Wang , Ming Lei","doi":"10.1016/j.clim.2025.110474","DOIUrl":"10.1016/j.clim.2025.110474","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study was to systematically assess the relationship between Chitinase 3-like protein-1 (CHI3L1) protein and disease progression in multiple myeloma (MM) and to explore its potential clinical value as a biomarker to provide a basis for optimizing treatment strategies.</div></div><div><h3>Methods</h3><div>136 patients with MM were divided into two groups according to the efficacy: group 1–95 patients with non-progressing MM; group 2–41 patients with progressing MM. The concentration of CHI3L1 in the serum of the patients was determined by enzyme-linked immunosorbent assay (ELISA).</div></div><div><h3>Results</h3><div>CHI3L1 concentration in patients' serum was significantly greater than in healthy controls (<em>P</em> < 0.001), which patients with International Staging System (ISS) III had significantly higher CHI3L1 concentration than those with stage I/II. Patients in the progressed group had significantly higher CHI3L1 concentration than those in the non-progressed group by comparative analyses. Otherwise, multifactorial logistic regression analyses showed that CHI3L1 concentration was an independent predictor of MM progression after other confounding factors were excluded, and that the risk of progression in the high-concentration group was increased by 243.6 %, relative to the low-concentration group. Moreover, smoothed curve fitting analysis further confirmed that serum CHI3L1 concentration was linearly related to the probability of progression in MM patients, and the risk of progression increased as CHI3L1 concentration increased.</div></div><div><h3>Conclusions</h3><div>This study indicated that CHI3L1 concentration in the serum of MM patients was closely correlated with disease severity. High concentration CHI3L1 predicted the progression of MM disease, suggesting its clinical application potential in predicting disease prognosis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110474"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673288","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 : 2025-03-17DOI: 10.1016/j.clim.2025.110475
Benjamin L. Spector , Boryana S. Koseva , Drinnan Sante , Warren A. Cheung , Reid S. Alisch , Alexander Kats , Phillip Bergmann , Elin Grundberg , Gerald J. Wyckoff , Laurel K. Willig
Cell-free DNA (cfDNA) is a marker of organ injury and immune response. DNA methylation is an epigenetic regulator of gene expression. Here, we elucidate total plasma cfDNA methylation from kidney transplant recipients in presence versus absence of rejection. In doing so, we exploit cfDNA as a real-time biomarker to define molecular pathways of rejection. Twenty plasma cfDNA samples from pediatric kidney transplant recipients were collected at allograft biopsy. Differentially methylated cytosine residues (>20 % methylation difference, q-value <0.05) were identified in presence (N = 7) versus absence (N = 9) of acute rejection. Separate analyses were performed comparing borderline rejection (N = 4) to rejection and non-rejection. In rejection versus non-rejection, there were 1269 differentially methylated genes corresponding to 533 pathways. These numbers were 4-13× greater than comparisons against borderline samples. Enriched pathways between rejection and non-rejection samples were related to immune cell/inflammatory response, lipid metabolism, and tryptophan-kynurenine metabolism, suggesting differential methylation of these pathways contributes to rejection.
{"title":"Total plasma cfDNA methylation in pediatric kidney transplant recipients provides insight into acute allograft rejection pathophysiology","authors":"Benjamin L. Spector , Boryana S. Koseva , Drinnan Sante , Warren A. Cheung , Reid S. Alisch , Alexander Kats , Phillip Bergmann , Elin Grundberg , Gerald J. Wyckoff , Laurel K. Willig","doi":"10.1016/j.clim.2025.110475","DOIUrl":"10.1016/j.clim.2025.110475","url":null,"abstract":"<div><div>Cell-free DNA (cfDNA) is a marker of organ injury and immune response. DNA methylation is an epigenetic regulator of gene expression. Here, we elucidate total plasma cfDNA methylation from kidney transplant recipients in presence versus absence of rejection. In doing so, we exploit cfDNA as a real-time biomarker to define molecular pathways of rejection. Twenty plasma cfDNA samples from pediatric kidney transplant recipients were collected at allograft biopsy. Differentially methylated cytosine residues (>20 % methylation difference, <em>q</em>-value <0.05) were identified in presence (<em>N</em> = 7) versus absence (<em>N</em> = 9) of acute rejection. Separate analyses were performed comparing borderline rejection (<em>N</em> = 4) to rejection and non-rejection. In rejection versus non-rejection, there were 1269 differentially methylated genes corresponding to 533 pathways. These numbers were 4-13× greater than comparisons against borderline samples. Enriched pathways between rejection and non-rejection samples were related to immune cell/inflammatory response, lipid metabolism, and tryptophan-kynurenine metabolism, suggesting differential methylation of these pathways contributes to rejection.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"275 ","pages":"Article 110475"},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662964","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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