Journal of Clinical Immunology最新文献

{"title":"Correction to: A Multicentric Clinical Study to Evaluate Pharmacokinetics, Efficacy, and Safety of Immune Globulin Subcutaneous 20% Weekly/Biweekly Dosing in Treatment-Experienced Patients and Loading/Weekly Maintenance Dosing in Treatment-Naïve Patients with Primary Immunodeficiency.","authors":"William R Lumry, Michael Palumbo, Connie Hsu, Iftikhar Hussain, Donald McNeil, Tracy Bridges, H James Wedner, Mark Scarupa, Elsa Mondou, Nisha Nanaware-Kharade, Kim Hanna, Montse Querolt Coll, Juan Oliveras","doi":"10.1007/s10875-026-01983-6","DOIUrl":"10.1007/s10875-026-01983-6","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":"15"},"PeriodicalIF":4.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12864319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case-Based Literature Review of RELA Associated Inflammatory Diseases.","authors":"Nihal Karaçayır, Merve Yazol, Emine Nur Sunar Yayla, Pelin Esmeray Şenol, Çisem Yıldız, Nuran Belder, Merve Kutlar, Batuhan Küçükali, Büşra Acun, Deniz Gezgin Yıldırım, Sevcan A Bakkaloğlu","doi":"10.1007/s10875-025-01968-x","DOIUrl":"10.1007/s10875-025-01968-x","url":null,"abstract":"<p><p>Behçet's disease (BD) is a chronic inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and uveitis. Recent genetic studies have identified monogenic diseases with phenotypes resembling BD, including RELA-associated inflammatory disease (RAID), Haploinsufficiency of A20 (HA20), and otulipenia. The RelA gene encodes the RELA protein, which is involved in the nuclear factor kappa B (NF-κB) signaling pathway that regulates the transcription of genes associated with cell survival, apoptosis, and immune responses. In RAID, dysfunction of the NF-κB pathway leads to reduced cell survival and symptoms of BD, such as recurrent fever, chronic mucocutaneous ulceration, arthralgia, and colitis. Herein, we report a pediatric patient who presented with recurrent, severe oral and genital ulcers from the age of five years and was diagnosed with RAID following a documented RelA gene mutation. The patient responded to a combination of corticosteroids, colchicine and methotrexate. RAID should be considered in the differential diagnosis of patients with early onset recurrent fever and mucosal ulcerations.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"17"},"PeriodicalIF":4.1,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: An international survey of allogeneic hematopoietic cell transplantation for X-linked agammaglobulinemia.","authors":"Akira Nishimura, Ramya Uppuluri, Revathi Raj, Venkateswaran Vellaichamy Swaminathan, Yifei Cheng, Rolla F Abu-Arja, Bin Fu, Alexandra Laberko, Michael H Albert, Fabian Hauck, Giorgia Bucciol, Venetia Bigley, Suzanne Elcombe, Gaurav Kharya, Cornelis Jan H Pronk, Claudia Wehr, Bénédicte Neven, Klaus Warnatz, Isabelle Meyts, Tomohiro Morio, Andrew R Gennery, Hirokazu Kanegane","doi":"10.1007/s10875-026-01982-7","DOIUrl":"10.1007/s10875-026-01982-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":"11"},"PeriodicalIF":5.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12823741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Deficiency in Xeroderma Pigmentosum.","authors":"Raphael Rossmanith, Christoph B Geier, Robert W Gruber, Hermann M Wolf","doi":"10.1007/s10875-025-01967-y","DOIUrl":"10.1007/s10875-025-01967-y","url":null,"abstract":"<p><p>We describe a 3-year-old patient with xeroderma pigmentosum (XP) and genetically confirmed XPA deficiency who presented with recurrent infections in early childhood. Immunological assessment revealed mild hypogammaglobulinemia with IgG2 and IgG3 subclass deficiencies, as well as impaired humoral immunity demonstrated by a reduced antibody response to repeated vaccinations against bacterial antigens. Flow cytometric analysis further showed an altered distribution of peripheral T helper (TH) cell subsets. In addition, we report a second case: a 33-year-old XP patient with ERCC4 deficiency who also exhibited IgG3 subclass deficiency and reduced response to booster vaccination. Functional studies revealed defective nucleotide excision repair (NER) following UV-C exposure, along with reduced B-cell activation capacity. These findings suggest a potential link between XP and immunoglobulin subclass deficiencies, indicating a susceptibility to infections in affected individuals. We therefore recommend that patients diagnosed with XP undergo comprehensive immunological evaluation to allow early detection of immunodeficiency and timely intervention, including booster vaccinations or prophylactic measures such as low-dose antibiotics or immunoglobulin replacement therapy when indicated.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":"4"},"PeriodicalIF":5.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional Assessment of Patient-Reported-Outcomes in a Multicenter Cohort of Inborn Errors of Immunity.","authors":"Melek Yorgun Altunbas, Asena Pinar Sefer, Sevgi Bilgic-Eltan, Cebbar Yildirimcakar, Pelin Ozturk, Ümmügülsüm Dikici, Ece Tüsüz Önata, Özge Atik, Hatice Eke-Gungor, Burcu Kolukisa, Hayrunnisa Bekis Bozkurt, Gaye Kocatepe, Şefika İlknur Kökcü Karadağ, Aysu İlhan Yalaki, Zeycan Canitez Oral, Nagihan Iskender, Tuğba Kıratlı Kıratlı Yolcu, Dilan Şirin, Reyhan Gumusburun, Demet Tekcan, Iknur Kulhas Celik, Salim Can, Razin Amirov, Necmiye Ozturk, Selcen Bozkurt, Burkay Cagan Colak, Ramin Mahmudov, Ezgi Yalcın Gungoren, Esra Karabiber, Hasibe Artac, Omur Ardeniz, Isıl Eser Simsek, Fatih Çelmeli, Tuğba Arikoglu, Deniz Özçeker, Dilara Kocacik Uygun, Aysen Bingol, Fatma Merve Tepetam, Öner Özdemir, Muhlis Cem Ar, Ebru Arik Yilmaz, Ahmet Ozen, Safa Baris, Elif Karakoc-Aydiner","doi":"10.1007/s10875-025-01972-1","DOIUrl":"10.1007/s10875-025-01972-1","url":null,"abstract":"<p><p>Patient-reported outcomes are critical to multidisciplinary, patient-centred approaches in diseases requiring lifelong management. Among inborn errors of immunity (IEIs), reports on this subject are typically limited to specific diagnostic subgroups or focus narrowly on the route of immunoglobulin replacement therapy (IgRT), offering a restricted perspective. We aimed to evaluate the health-related quality of life (HRQoL) and IgRT-related treatment satisfaction (TS) of a heterogeneous cohort of IEI patients and identify factors influencing these outcomes to guide improving the health and well-being of IEI patients. We conducted a cross-sectional survey targeting IEI patients on IgRT, assessing TS (TSQM-9) and HRQoL (KINDL/SF-36). Patient/caregiver-reported data were integrated with clinical data to identify outcomes and influencing factors. The survey included 500 IEI patients (356 children, 144 adults) diagnosed 54% Primary Antibody Deficiency (PAD), 36% combined immunodeficiency, 7% immune-dysregulation, and 3% other IEIs. Non-PAD diagnoses, comorbidities, absence of school/work attendance, and IgRT-related systemic adverse reactions negatively impacted HRQoL. Severe infections and related hospitalizations adversely influenced both HRQoL and TS. The subcutaneous route of IgRT, particularly at home, was associated with higher TS due to its convenience and reduced school/work absenteeism. However, the IgRT route did not influence adult HRQoL. Patient-reported well-being and satisfaction in IEIs are multifactorial and cannot be solely attributed to the route of IgRT. Minimizing negative experiences related to the disease or its treatment and, where possible, encouraging patients to maintain school/work attendance or engage in activities that promote societal participation can enhance self-esteem, coping abilities, and overall well-being.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"18"},"PeriodicalIF":4.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFRSF13B Variant-Induced TACI Dysregulation Underlies CAEBV Pathogenesis.","authors":"Xinyue Deng, Qiang Gao, Kefeng Shen, Wei Mu, Tong Ge, Jia Gu, Xiuxiu Yang, Jiali Cheng, Jiachen Wang, Wei Zhang, Dengju Li, Jianfeng Zhou, Min Xiao","doi":"10.1007/s10875-025-01973-0","DOIUrl":"10.1007/s10875-025-01973-0","url":null,"abstract":"<p><p>The tumor necrosis factor (TNF) receptor superfamily member, transmembrane activator and CAML interactor (TACI) encoded by TNFRSF13B, are extensively involved in immune responses. In our previous work, TNFRSF13B exon 2 variants were recurrently identified in chronic active Epstein-Barr virus disease (CAEBV). Here we aim to reveal the roles of TNFRSF13B variants in CAEBV, and investigate the feasibility of targeting TNFRSF13B/TACI as a new approach to control EBV infection. The lymphoblastoid cell lines (LCL) models carrying homozygous TNFRSF13B exon 2 frameshift mutations were constructed using CRISPR/Cas9. Immunological assays, transcriptomic analysis, and gene silencing experiments were performed on LCL models to measure the effect of TNFRSF13B exon 2 variants and explore the underlying mechanisms. TACI ligands and a TLR9 agonist were applied to modulate TACI signaling and EBV activities. Frameshift mutations in exon 2 of TNFRSF13B significantly up-regulated the short isoforms of TACI (TACI-S) at the expense of its long isoforms (TACI-L) in LCLs. The up-regulated TACI-S induced more intense activation of NF-κB, MAPK, and Rho signaling pathways, leading to the switch of EBV activities to lytic reactivation. The subsequent increased viral load and viral IL-10 provide a rational for the susceptibility of variant carriers to CAEBV. The BAFF trimer, an indirect TACI-signaling inhibitor, also significantly suppressed the EBV lytic program. Gene silencing experiments indicated that XBP-1 might be involved in the TACI-mediated regulation of EBV lytic activities in EBV-immortalized B cells. This study underscores the impact of TNFRSF13B variants on EBV infection and host immune responses, offering insights into CAEBV pathogenesis and potential therapeutic strategies.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"12"},"PeriodicalIF":5.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Signatures of Smoking: Cytokine and Immunoglobulin Dysregulation and Partial Reversibility in a Population-Based Study.","authors":"Samantha E Leonard, Mohsen Ghanbari, Lies Lahousse, Joyce B J van Meurs, P Martin van Hagen, Layal Chaker, Virgil A S H Dalm","doi":"10.1007/s10875-025-01975-y","DOIUrl":"10.1007/s10875-025-01975-y","url":null,"abstract":"<p><p>While smoking-induced epigenetic changes are increasingly recognized, the relationship between varying smoking history and immune protein profiles remains incompletely understood. This study investigates associations between smoking history and circulating inflammatory cytokines and serum immunoglobulins, and explores DNA methylation as a potential mediator. We analyzed 2,119 participants from the Rotterdam Study, examining associations of smoking duration, pack-years, and cessation time with plasma inflammatory proteins, including six pro- and three anti-inflammatory cytokines (Olink) and three serum immunoglobulins (IgA, IgG, and IgM). Cytokines were z-transformed and multivariable (non)linear regression models were applied, adjusted for age, sex, BMI, alcohol use, and socioeconomic status. A distinct immune signature emerged, with (z-transformed) IL-6, IL-18, IL-17C, and IL-10 levels increasing with pack-years and smoking duration (β range: 0.0029 to 0.015). IgA and IgG displayed reverse J-shaped associations with pack-years (β range: –0.050 to 0.048) and levels declined with smoking duration (β = –0.0067 and –0.028, respectively). IL-6, IL-17A, and IL-10 decreased with cessation time (β range: -0.007 to -0.004), and IgG increased (β = 0.018). IgM responses differed by sex. Mediation analysis using PCA-derived CpG components did not support a role for DNA methylation in these associations. These findings reveal dose-dependent, pro-inflammatory immune dysregulation with cumulative smoking exposure and partial reversibility of IL-6 and IgG following cessation. The absence of mediation by DNA methylation suggests other pathways are involved. These findings support the use of cytokines and immunoglobulins as biomarkers for immune surveillance and recovery monitoring, reflecting an underlying inflammatory smoking signature.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"9"},"PeriodicalIF":4.1,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Distinct Monocyte Subsets and Intercellular Communication in Primary Sjögren's Syndrome Revealed by Single-Cell RNA Sequencing.","authors":"Xiaoyu Zhang, Xiangrong Song, Li Fang, Bo Zang, Jiaxiu Li, Yifei Yang, Meng Xu, Yuanwei Han, QiXuan Liu, Hong Zhu, Bin Liu","doi":"10.1007/s10875-025-01974-z","DOIUrl":"10.1007/s10875-025-01974-z","url":null,"abstract":"<p><strong>Objective: </strong>The presence of unique monocyte subsets and sub-populations plays a significant role in the onset and progression of rheumatic diseases. This study aimed to characterize variations in monocyte subsets and sub-populations and functional roles in patients with primary Sjögren's syndrome (pSS) using single-cell RNA sequencing (scRNA-seq).</p><p><strong>Method: </strong>Monocyte samples from patients with pSS and healthy controls (HCs) were analyzed using single-cell RNA sequencing (scRNA-seq). This approach identified divergent gene expression patterns, transcription factors, and immune cells interactions within monocyte subset and sub-populations, highlighting pathways potentially involved in the pathogenesis of pSS.</p><p><strong>Results: </strong>The scRNA-seq analysis delineated three major monocyte subsets: classical monocytes (CD14⁺⁺CD16^-), non-classical monocytes (CD14^-CD16⁺), and cDC2, with further identification of sub-populations within the classical and non-classical monocyte subsets. A notable increase in the proportions of classical monocyte sub-population 2 and non-classical monocyte sub-population 2 was observed in pSS patients. Compared to the HCs, pSS patients exhibited enhanced immune cell interactions within monocyte subsets. Furthermore, in pSS patients, the dominant increased pathways within monocytes were those related to viral responses, interferon activity, and oxidative phosphorylation. Additionally, significantly elevated expression levels of IFI44, IFI44L, HBA2, LY6E, XAF1, EPSTI1, APOBEC3A, and IFIT3 were identified in pSS monocytes.</p><p><strong>Conclusion: </strong>This research revealed irregular alterations in monocyte subsets and sub-populations, transcription factors, and gene expression patterns within pSS patients, pinpointing prospective biomarkers in pSS as viable targets for therapeutic intervention.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"10"},"PeriodicalIF":5.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Related Patterns of Type II Interferon Immunity: Implications for Intramacrophagic Infections and MSMD Diagnosis During Childhood.","authors":"Yiyi Luo, Guillermo Argüello, Daniel Acevedo, Cristina Jou, Anna Codina, Jesús Márquez, Alexandru Vlagea, Sara Peiró, Víctor Bolaño, Aina Freixedas, Angela Deyà-Martínez, Ana García-García, Celia Martí-Castellote, Manel Juan, Ana Esteve-Solé, Laia Alsina","doi":"10.1007/s10875-025-01955-2","DOIUrl":"10.1007/s10875-025-01955-2","url":null,"abstract":"<p><p>Type II interferon (IFN) immunity is crucial for controlling intramacrophagic infections, driven by the interaction between innate immunity (macrophage-derived IL-12) and adaptive immunity (Th-derived IFN-γ). This study examines the maturation of type II IFN immunity in 55 healthy children (ages 1-18) to enable proper identification of deficiencies as part of the diagnostic evaluation of Mendelian Susceptibility to Mycobacterial Diseases (MSMD). The IL-12/IFN-γ axis was assessed through: (1) cytokine production after mycobacterial stimulation (Luminex and ELISA for IFN-γ, IL-12p70, TNF, CXCL10, IL-1RA, IL-10, IL-1β and IL-6), (2) IFN-γR1/R2 expression on monocytes, and (3) STAT1 phosphorylation/dephosphorylation. T cell maturation (primary IFN-γ source) was evaluated via immunophenotyping (naïve/memory/activated, Th1; Th2; Th17; Th1/17; Tfh) and proliferation assays. Main findings: (1) stable expression/production of key components of the IL-12/IFN-γ axis (IFN-γ, IL-12, TNF, IFN-γR1/2, and STAT1 activity) across ages confirming the stability of innate immune function throughout childhood; (2) increasing responses to IFN-γ with age reflected by increased CXCL10 production, and increase in the IFN-γ counter-acting anti-inflammatory cytokines (IL-10, IL-1RA); and (3) progressive T cell maturation, including Th1, Th17 and Th1/17 subsets, with significant milestones between 6 and 8.6 years, while T cell proliferative capacity remained stable. These observations highlight the stability of IL-12/IFN-γ axis innate components with age, accompanied by enhanced downstream IFN-γ signaling, aligning with the maturation of Th cell compartment. These underscore the limited benefit of age-specific controls in the evaluation of IL-12/IFN-γ axis in MSMD diagnosis, while emphasizing the importance of T cell maturation in the overall type II IFN immunity.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"13"},"PeriodicalIF":5.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signatures of Trained Immunity Following mRNA Vaccination: Differences Between mRNA-1273 and BNT162b2.","authors":"Martin Kunc, Bradley Joseph Whitehead, Lars Jørgen Østergaard, Martin Tolstrup, Christine Stabell Benn, Christian Morberg Wejse, Peter Nejsum","doi":"10.1007/s10875-025-01977-w","DOIUrl":"10.1007/s10875-025-01977-w","url":null,"abstract":"<p><p>Trained immunity, a de-facto innate immune memory, has been extensively studied in response to live-attenuated vaccines, but its presence following the new COVID-19 vaccines has not yet been fully elucidated. In this study, we investigate markers of trained immunity in individuals vaccinated with mRNA-1273 or BNT162b2. As part of the vaccine roll-out in Denmark and recruited for a comparative study. Our primary objective was to determine whether these vaccines elicit lasting changes in innate immune responses, particularly in monocyte populations and cytokine production following stimulation with a panel of agonists. The study was conducted at four time points: Day-0 (pre-vaccination), Day-28, Day-90, and Day-180 post-vaccination. We observed no significant differences in monocyte subpopulations between vaccine groups; however, cytokine and chemokine analysis revealed distinct immune signatures. While IL-6 and TNFα production remained unchanged after ex-vivo restimulation in the BNT162b2 group, individuals vaccinated with mRNA-1273 exhibited a sustained increase in the production of these cytokines, persisting for up to 180 days post-vaccination. Additionally, CCL2, a key chemokine involved in monocyte recruitment, was upregulated following mRNA-1273 vaccination but decreased in the BNT162b2 group, further supporting the finding of differential innate immune responses between the two vaccines. In conclusion, our study provides evidence that mRNA-1273, but not BNT162b2, induces immune responses consistent with the concept of trained immunity. These results highlight the potential for mRNA vaccine platforms to shape innate immunity, with implications for future vaccine design aimed at enhancing non-specific and specific protection against infectious diseases.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":"8"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12815979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}