Clinical immunologyPub Date : 2026-02-01Epub Date: 2025-12-21DOI: 10.1016/j.clim.2025.110659
Temesgen E. Andargie , Han Su , Moon Kyoo Jang , Xin Tian , Andrew H. Karaba , Sean Agbor-Enoh
{"title":"Systemic cytokine profiling enhances the performance of dd-cfDNA to detect cardiac rejection","authors":"Temesgen E. Andargie , Han Su , Moon Kyoo Jang , Xin Tian , Andrew H. Karaba , Sean Agbor-Enoh","doi":"10.1016/j.clim.2025.110659","DOIUrl":"10.1016/j.clim.2025.110659","url":null,"abstract":"<div><div>The association between circulating cytokines and allograft injury due to allograft rejection (AR) remains poorly defined. We hypothesize that cytokines correlate with the degree of allograft injury during AR. This case-control study measured cytokines and cell-free DNA in 88 heart transplant plasma samples (54 AR, 34 non-rejecting (NR) controls) and 26 healthy controls. AR patients exhibited higher levels of total and percent donor-derived cfDNA (%dd-cfDNA) and proinflammatory cytokines, and lower levels of type II cytokines/chemokines and Th17/23 axis cytokines compared to NR or HCs. The cfDNA levels positively correlated with proinflammatory cytokines and negatively with MDC and cytokines of the Th17/IL-23 axis. A Lasso regression model combining cytokines and %dd-cfDNA (AUC = 0.93) showed better AR diagnostic performance than either cytokines or %dd-cfDNA alone. The study concluded that inflammatory and regulatory cytokine levels correlate with allograft injury, and combining cytokines with %dd-cfDNA may enhance AR detection.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110659"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817674","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}
{"title":"Cross-reactive HERV-W and EBV peptides elicit antibody responses in MS patients and synergistically exacerbate neuroinflammation in EAE","authors":"Davide Cossu , Yuji Tomizawa , Tamami Sakanishi , Stefano Ruberto , Taku Hatano , Nobutaka Hattori","doi":"10.1016/j.clim.2025.110644","DOIUrl":"10.1016/j.clim.2025.110644","url":null,"abstract":"<div><div><em>Human endogenous retrovirus W</em> (HERV-W) has been linked to multiple sclerosis (MS), yet its pathogenic role remains unclear. <em>Epstein–Barr virus</em> (EBV), a key MS risk factor, can transactivate HERVs, suggesting a potential interplay. We analyzed immune responses to a HERV-W₁₀₃–₁₁₀ peptide homologous to EBV EBNA1₃₈₆–₄₀₅ in sera from Japanese MS patients (<em>n</em> = 44), neurological controls (<em>n</em> = 28), and healthy controls (<em>n</em> = 48), including an unrelated control antigen (BCG) to assess general humoral activation. MS patients exhibited elevated antibodies to both peptides, indicating cross-reactive immunity. In C57BL/6 J mice, pre-immunization with either peptide modestly modulated experimental autoimmune encephalomyelitis (EAE), whereas combined pre-immunization exacerbated disease, expanding CD4<sup>+</sup> and CD8<sup>+</sup> T cells and promoting systemic activation. These results support a model in which EBV-driven HERV-W activation elicits cross-reactive humoral and cellular responses that amplify neuroinflammation in MS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110644"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594800","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}
Clinical immunologyPub Date : 2026-02-01Epub Date: 2025-12-16DOI: 10.1016/j.clim.2025.110657
Hui Wu , Xianglin Chu , Huahua Zhong , Ying Huang , Hongxia Yang , Guoyan Qi , Lei Jin , Ran Chen , Wenji Jia , Ji Xiong , Liewen Pang , Chongbo Zhao , Jie Song , Sushan Luo
{"title":"Eculizumab as a new option for perioperative treatment in thymoma-associated myasthenia gravis","authors":"Hui Wu , Xianglin Chu , Huahua Zhong , Ying Huang , Hongxia Yang , Guoyan Qi , Lei Jin , Ran Chen , Wenji Jia , Ji Xiong , Liewen Pang , Chongbo Zhao , Jie Song , Sushan Luo","doi":"10.1016/j.clim.2025.110657","DOIUrl":"10.1016/j.clim.2025.110657","url":null,"abstract":"<div><div>The efficacy of eculizumab as a perioperative treatment in patients with thymoma-associated myasthenia gravis (TAMG) has not been evaluated. This prospective study included patients with TAMG who received standard-of-care therapy (Soc group, <em>n</em> = 20) or combined with eculizumab (Ecu group, <em>n</em> = 13). At 1 week, the Ecu group showed a marked improvement compared to the Soc group, as evidenced by a reduction in Quantitative Myasthenia Gravis (QMG) (7.39 ± 3.47 vs 0.25 ± 5.13, <em>P</em> <em>=</em> 0.0001), Manual Muscle Test (MMT) (6.39 ± 4.66 vs 0.15 ± 3.96, <em>P</em> = 0.0003), and MG Activities of Daily Living (MG-ADL) (4.85 ± 3.16 vs 0.30 ± 3.47, <em>P</em> = 0.0006). No significant differences were observed in operative time, or intraoperative blood loss. The rate of postoperative myasthenic crisis was 9.1 % (1/13) in the Ecu group, compared to 20 % (4/20) in the Soc group (<em>P</em> = 0.33). This study highlights the role of eculizumab in TAMG as a rapid symptom-control treatment before thymomectomy.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110657"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780555","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}
Clinical immunologyPub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.clim.2025.110655
Qianwen Tian , Qi Xi , Qiaolin Zhang , Yun Chen , Yunxin Zhang , Fuxue Kuang , Lejie Sun , Song Peng , Huaxun Wu
{"title":"Regulation of Ro52/SSA autoantigen by endoplasmic reticulum stress and ERK1/2-mTOR-autophagy signaling pathway in primary Sjögren disease","authors":"Qianwen Tian , Qi Xi , Qiaolin Zhang , Yun Chen , Yunxin Zhang , Fuxue Kuang , Lejie Sun , Song Peng , Huaxun Wu","doi":"10.1016/j.clim.2025.110655","DOIUrl":"10.1016/j.clim.2025.110655","url":null,"abstract":"<div><div>Primary Sjögren disease (pSS) is an autoimmune disease characterized primarily by predominant lymphocytic infiltration of the exocrine glands. While the etiopathogenesis of pSS remains unclear, current therapeutic strategies lack efficacy. In human submandibular gland epithelial cells (HSGECs), endoplasmic reticulum stress (ERS) induces apoptosis, leading to the cellular redistribution of Ro52/SSA autoantigens, the activation of the immune system, and the production of a large number of autoantibodies. Cells initiate autophagy to resist cellular damage caused by ERS and restore the normal physiological status. The ERK1/2-mTOR-autophagy signaling pathway has been implicated in numerous pathological conditions. In this study, an experimental Sjögren disease (ESS) mouse model was established to evaluate reduced protein levels and altered intracellular distribution of Ro52/SSA autoantigens through modulation of ERS and the ERK1/2-mTOR-autophagy pathway, resulting in diminished autoantibody production and ameliorated ESS symptoms. These findings provide an experimental foundation for therapeutic strategies targeting Ro52/SSA production in pSS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110655"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751748","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}
Clinical immunologyPub Date : 2026-02-01Epub Date: 2025-10-31DOI: 10.1016/j.clim.2025.110632
Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen
{"title":"Natural history of clinical manifestations in activated phosphoinositide 3-kinase δ syndrome (APDS): Time-to-event analyses using the European Society for Immunodeficiencies-APDS registry","authors":"Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen","doi":"10.1016/j.clim.2025.110632","DOIUrl":"10.1016/j.clim.2025.110632","url":null,"abstract":"<div><div>Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110632"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430450","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}
Clinical immunologyPub Date : 2026-02-01Epub Date: 2025-11-29DOI: 10.1016/j.clim.2025.110653
Fatima Hubaishi , Rami Karkout , Lydia Labrie , Raidan Mohammed Alyazidi , Magan Solomon , Haya Aldossary , Brian J. Ward , Elizabeth D. Fixman
{"title":"Epicutaneous application of house dust mite induces allergic skin inflammation and atopic march to the lung upon airway allergen challenge","authors":"Fatima Hubaishi , Rami Karkout , Lydia Labrie , Raidan Mohammed Alyazidi , Magan Solomon , Haya Aldossary , Brian J. Ward , Elizabeth D. Fixman","doi":"10.1016/j.clim.2025.110653","DOIUrl":"10.1016/j.clim.2025.110653","url":null,"abstract":"<div><div>Atopic dermatitis (AD) in infants is associated with increased risk of developing other allergic diseases, including asthma. This progression is known as atopic march (AM). We established a murine AM model by first inducing AD-like skin inflammation to house dust mite (HDM) allergen. Mice were subsequently challenged with HDM delivered to the lung. Our data show that epicutaneous sensitization with HDM increased serum IgE, ear thickness, and immune cell infiltration into the skin, accompanied by an increase in CD4<sup>+</sup> tissue-resident memory T cells (Trm) in the lung. Following pulmonary HDM challenge, eosinophil influx and T2 inflammation were increased in the lung. Together, our data suggest communication between the skin and lung, where allergen sensitization on the skin increases lung Trm and amplifies the T2 allergic response to lung allergen challenge. This clinically relevant model could help identify novel targets for local interventions to reduce the progression of AD to asthma.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110653"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647587","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}
Clinical immunologyPub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.clim.2025.110642
Josephine Diony Nanda , Tzong-Shiann Ho , Rahmat Dani Satria , Yung-Ting Wang , Chun-Hao Lai , Ya-Lan Lin , Chiou-Feng Lin
{"title":"An integrated biomarker panel for early computational prediction of dengue severity during the acute phase","authors":"Josephine Diony Nanda , Tzong-Shiann Ho , Rahmat Dani Satria , Yung-Ting Wang , Chun-Hao Lai , Ya-Lan Lin , Chiou-Feng Lin","doi":"10.1016/j.clim.2025.110642","DOIUrl":"10.1016/j.clim.2025.110642","url":null,"abstract":"<div><div>Serum cytokines and chemokines play a pivotal role in dengue immunopathogenesis and may serve as biomarkers of disease severity. This study aimed to identify applicable blood biomarkers during the acute stage of infection to support early severity evaluation using Principal Component Analysis (PCA)–based feature integration. Ninety-two dengue patients were consecutively enrolled from hospital admissions with laboratory-confirmed dengue during the 2015–2017 epidemic. Only those with NS1-positive or PCR-positive cases were included in this study, spanning asymptomatic, symptomatic, and severe cases, which were assessed for hematological, viral, and cytokine/chemokine parameters. Key variables—platelet count, GPT, creatinine, NS1, NST, IL-18, RANTES, IL-6, IFN-α2, and IL-7—were incorporated into a Prediction Panel. Validation showed that several biomarker combinations achieved up to 90 % accuracy in distinguishing severity groups, while others reached ∼70 %. Principal component analysis further refined the panel, showing accuracy above 90 % when NS1 or NST were included (A–B: 92.1 %, A–C: up to 91.8 %). These findings highlight the potential of an integrated biomarker-based Prediction Panel for early and reliable assessment of dengue severity within the first week of illness.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110642"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562981","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}
Clinical immunologyPub Date : 2026-01-01Epub Date: 2025-11-01DOI: 10.1016/j.clim.2025.110633
Gabrielle Magdalena Tan , Kiran Sehmi , Sarah Azzi , Robert Hostoffer
{"title":"High-titer IVIG 10 % (human)–slra reduces infections and hospitalizations over 6 to 12 months: A retrospective quality improvement study","authors":"Gabrielle Magdalena Tan , Kiran Sehmi , Sarah Azzi , Robert Hostoffer","doi":"10.1016/j.clim.2025.110633","DOIUrl":"10.1016/j.clim.2025.110633","url":null,"abstract":"<div><div>Patients with primary or secondary immunodeficiencies are at an increased risk for recurrent respiratory infections despite standard intravenous immunoglobulin (IVIG) therapy. This retrospective quality improvement review evaluated the clinical impact of a high-titer IVIG product enriched with pathogen-specific antibodies in 14 patients after failing conventional IVIG. The primary outcomes were changes in infection frequency and hospitalization rates during the 6 months before and after treatment initiation, and from 6 months post-treatment to the present. Ten patients (71%) showed clinical improvement, with infections decreasing from 36 to 8 and hospitalizations from 14 to 5 in the first 6 months post-treatment; benefits were more pronounced when excluding one clinical outlier. Two patients discontinued therapy due to mild adverse effects or lack of efficacy. High-titer IVIG was associated with meaningful reductions in infection burden and hospitalizations, supporting its consideration for high-risk patients unresponsive to standard IVIG.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110633"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430445","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}
Clinical immunologyPub Date : 2026-01-01Epub Date: 2025-11-14DOI: 10.1016/j.clim.2025.110639
Aidé Tamara Staines-Boone , Edna Venegas-Montoya , Jorge Alberto García Campos , Jennifer Alejandra Obregón García , Julieta C. Marmolejo Bjirsdorp , Yuridia Salazar Gálvez , Mario Ernesto Cruz-Muñoz , Lizbeth Blancas Galicia , Edgar Alejandro Medina-Torres , Sara Elva Espinosa-Padilla , Diana Olguín Calderón , Laura Berrón-Ruiz , Saul O. Lugo Reyes
{"title":"Job's not done: BCG-itis as the first manifestation of hyper-IgE syndrome. A case report and review of the literature","authors":"Aidé Tamara Staines-Boone , Edna Venegas-Montoya , Jorge Alberto García Campos , Jennifer Alejandra Obregón García , Julieta C. Marmolejo Bjirsdorp , Yuridia Salazar Gálvez , Mario Ernesto Cruz-Muñoz , Lizbeth Blancas Galicia , Edgar Alejandro Medina-Torres , Sara Elva Espinosa-Padilla , Diana Olguín Calderón , Laura Berrón-Ruiz , Saul O. Lugo Reyes","doi":"10.1016/j.clim.2025.110639","DOIUrl":"10.1016/j.clim.2025.110639","url":null,"abstract":"<div><div>The <em>Bacille Calmette-Guérin</em> (BCG) vaccine is widely used to prevent tuberculosis (TB), especially in newborns and children in high TB prevalence areas. Though generally safe, it can cause adverse reactions like BCG-itis, a localized inflammatory response, and BCG-osis, a systemic infection. This case report details the clinical journey of a male toddler from a non-consanguineous family who presented with regional BCG-itis and later developed a disseminated mycobacterial infection. The patient had a history of recurrent suppurative otitis media and chronic granulomatous inflammation, with mycobacteria identified through biopsy. Despite initial treatments, he exhibited persistent and severe symptoms, including central nervous system abscesses, onychomycosis, and elevated serum Immunoglobulin E levels (13,160 IU/ml). Whole-exome sequencing identified a pathogenic heterozygous missense variant in <em>STAT3</em> exon 13 (c.1144C > T, p.Arg382Trp), confirming autosomal dominant Hyper-IgE Syndrome. The patient showed improvement with antibiotics and intravenous immunoglobulin, yet struggled with relapses upon dose reduction of antitubercular drugs. The literature review revealed two similar cases, underscoring the importance of genetic and immunological insights in managing adverse vaccine reactions in Hyper-IgE Syndrome. CD4+ Th17 cells and interleukins 17, 21, 22, and 23 are crucial in fighting mycobacteria by activating autophagy in infected monocytes and MAIT cells. Type 2 interferon immunity and superoxide production are key in combating mycobacterial diseases like Mendelian Susceptibility to Mycobacterial Disease and Chronic Granulomatous Disease. Studies show that Asian and Latin American patients are overrepresented in non-tuberculous mycobacterial infections due to mandatory BCG vaccination at birth. It is recommended to contraindicate BCG vaccination in patients with known or suspected immune deficiencies and delay live vaccines until 6 months of age.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110639"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534394","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}