Journal of Clinical Immunology最新文献

{"title":"Tofacitinib as a Successful Treatment for Hyper-IgE Syndrome and Autoimmunity Associated with Constitutive Activation of JAK3.","authors":"Yuxin Pei, Bei Jin, Reyila Abasi, Cheng Cheng, Hongjie Zhuang, Shuhan Zeng, Mengjie Jiang, Heying Pei, Xiaoyun Jiang","doi":"10.1007/s10875-026-02027-9","DOIUrl":"https://doi.org/10.1007/s10875-026-02027-9","url":null,"abstract":"<p><p>The Janus Kinase 3 (JAK3) germline gain-of-function (GOF) mutation is a rare inborn error of immunity, first reported in 2020, characterized by lymphopenia and chronic NK-cell proliferation. However, its role in autoimmunity remains unclear, and no direct association with hyper-IgE syndrome (HIES) has been established. In this study, we describe a patient presenting with HIES, myositis, lymphopenia, and autoimmune hypothyroidism. Whole-exome sequencing identified a novel compound heterozygous JAK3 mutation (c.2524_2525delinsTT and c.2805G > C), predicted to be deleterious. Flow cytometry and RNA sequencing of peripheral blood mononuclear cells revealed a significant reduction in T cells and NK cells, particularly naïve CD4⁺ T cells, accompanied by a marked imbalance in T cell subsets. This led to constitutive activation of JAK1 and JAK3, along with increased STAT3 and STAT5 phosphorylation. Tofacitinib treatment significantly improved the patient's symptoms. Our findings expand the clinical spectrum of JAK3-associated immune dysregulation, linking it for the first time to HIES and multiple autoimmune manifestations. Furthermore, this study suggests that tofacitinib may be a potential therapeutic option for JAK3 signaling-associated immune dysregulation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Profiling of T- and B-Cell Receptor Repertoires Demonstrates Impaired Developmental and Activation of Adaptive Immunity in DOCK8 Deficiency.","authors":"Tal Beit-Halevi, Arnon Broides, Atar Lev, Amos J Simon, Amit Nahum, Raz Somech, Yu Nee Lee","doi":"10.1007/s10875-026-02031-z","DOIUrl":"https://doi.org/10.1007/s10875-026-02031-z","url":null,"abstract":"<p><p>Dedicator of cytokinesis protein 8 (DOCK8) is a crucial regulator for the formation of immune synapses, allowing for a proper function of innate and adaptive immune systems. DOCK8 deficiency is a primary immunodeficiency, currently known as Inborn Errors of Immunity (IEI) affecting both cellular and humoral immunity, thus leading to various clinical presentations ranging from infections, autoimmunity, inflammations and malignancies. We aimed to identify unique molecular signatures in the adaptive immune repertoire of DOCK8-deficient patients through comprehensive sequencing and analysis of the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires, correlating these signatures with clinical features of the patients, ultimately providing a \"fingerprint\" of both individual's immunological status and disease conditions. We characterized the TCR repertoires of αβ T- and γδ T-cells, together with BCR repertoires of B-cells, in peripheral blood of 13 patients and age matched healthy donor controls using next generation sequencing. TCR repertoire in patients with DOCK8 deficiency demonstrated restricted diversity and clonal expansions, favorable use of specific gene in the V-D-J recombination process, and a unique finding of longer complementarity-determining-region-3 (CDR3) length, revealing an impaired T-cell development and activation. Furthermore, BCR repertoire demonstrated high diversity without clonal expansions, portraying an abnormal B-cell development leading to a possible mechanism for atopy and autoimmunity, alongside inadequate activation in DOCK8 deficiency. Lastly, various DOCK8 mutations demonstrated a more profound defects in immune repertoire. These findings expand our knowledge on the role DOCK8 plays in shaping the TCR and BCR repertoires in DOCK8 deficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults.","authors":"Seth Lederman, Bruce L Daugherty, Nancy Herje, Gregory M Sullivan","doi":"10.1007/s10875-026-02028-8","DOIUrl":"https://doi.org/10.1007/s10875-026-02028-8","url":null,"abstract":"<p><p>Blocking CD154 (CD40L) has the potential to prolong transplanted solid organ graft survival and treat autoimmune diseases. However, first-generation anti-CD154 IgG1 monoclonal antibodies (mAbs) were associated with an increased risk of thrombosis linked to Fc binding to FcγRIIa (CD32A). Here, we describe a first-in-human, phase 1 clinical trial of TNX-1500, a novel Fc-modified IgG4 anti-CD154 mAb designed to decrease binding to FcγRIIa. Healthy volunteers (N = 26) were enrolled into single-ascending dose (3, 10, and 30 mg/kg) cohorts and received TNX-1500 intravenously. TNX-1500 was generally well tolerated. Among participants receiving TNX-1500 3, 10, and 30 mg/kg, 1 (25%), 3 (38%), and 3 (38%) participants, respectively, reported ≥ 1 treatment-emergent adverse event; all were mild or moderate in severity, and none resulted in study discontinuation. There were no thromboembolic events. Pharmacokinetic analyses of TNX-1500 demonstrated a mean half-life of 37.8 and 33.8 days for 10 and 30 mg/kg, respectively, supportive of monthly dosing; dose-proportional exposure was suggested over the 3 to 30 mg/kg range. TNX-1500 blocked the primary T cell-dependent antibody response to keyhole limpet hemocyanin (KLH) at all doses and blocked the secondary response at the 10 and 30 mg/kg doses. At 3 mg/kg, TNX-1500 reduced peak secondary response to KLH by ~ 70% relative to placebo. TNX-1500 administration was associated with immediate and sustained reduction in soluble CD154. Overall, TNX-1500 demonstrated a safety profile and pharmacologic properties that support further development as an agent with potential for prevention of organ transplant rejection and treatment for autoimmune conditions.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Dysregulation and Persistent Symptoms: Insights into T Cell Dynamics in Post-COVID among Athletes from the CoSmo-S Study.","authors":"Miriam Ringleb, Daniel Alexander Bizjak, Andreas Michael Nieß, Hannah Notbohm, Hans-Georg Predel, Christian Puta, Jürgen Michael Steinacker, Manuel Widmann, Jonas Zacher, Wilhelm Bloch, Florian Javelle","doi":"10.1007/s10875-026-02020-2","DOIUrl":"10.1007/s10875-026-02020-2","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772928","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":"Three Doses and Six Months Later: Real-World SARS-CoV-2 Specific Humoral and Cell-Mediated Immunity in Children With Inborn Errors of Immunity.","authors":"Luana L T N Porto, Dina Yazji, Dana Unninayar, Hélène Decaluwe, Beata Derfalvi, Alejandro Palma, Thomas Issekutz, Tatiana Kalashnikova, Luis Murguía-Favela, Anne Pham-Huy, Tamar Rubin, Sneha Suresh, Julia Upton, Nicola A M Wright, Hugo Chapdelaine, Emilia Liana Falcone, Karina A Top, Manish Sadarangani, Donald C Vinh, Lisa Barrett, Sharon Oldford, Marc-Andre Langlois, Corey Arnold, Tinghua Zhang, Tim Ramsay, Juthaporn Cowan","doi":"10.1007/s10875-026-02021-1","DOIUrl":"https://doi.org/10.1007/s10875-026-02021-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic Stem Cell Transplantation Achieves Sustained Remission in Pediatric RAS-Associated Autoimmune Lymphoproliferative Disorder with Life-Threatening Complications: a Single-Center Case Series and Literature Review.","authors":"Yuchen Lin, Xia Qin, Chen Zhou, Uet Yu, Xiaohang Huang, Xinan Wang, Manpin Zhang, Chengjuan Luo, Changying Luo, Xiaodong Wang, Jing Chen","doi":"10.1007/s10875-026-02022-0","DOIUrl":"https://doi.org/10.1007/s10875-026-02022-0","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translating Host-Derived Signals from Cerebrospinal Fluid Metagenomic Sequencing into a Diagnostic Tool for Autoimmune Encephalitis in Children.","authors":"Dingding Han, Xiaozhou Pan, Fen Pan, Biyun Han, Qianyue Wu, Yiping Zhou, Huifang Liu, Huan Xu, Weifen Sun, Hongyi Cheng, Wenxin Liu, Rujia Wan, Wenhao Weng, Hong Zhang","doi":"10.1007/s10875-026-02023-z","DOIUrl":"https://doi.org/10.1007/s10875-026-02023-z","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TREM-1-Associated Neutrophil Extracellular Trap Formation is Linked to IVIG Resistance in Kawasaki Disease: A Convergent Transcriptomic and Prospective Validation Study.","authors":"Sibao Wang, Gang Luo, Zhixian Ji, Silin Pan","doi":"10.1007/s10875-026-02025-x","DOIUrl":"https://doi.org/10.1007/s10875-026-02025-x","url":null,"abstract":"<p><p>Kawasaki disease (KD) remains the leading cause of acquired heart disease in children. While intravenous immunoglobulin (IVIG) represents standard therapy, approximately 10-20% of patients exhibit treatment refractoriness associated with significantly elevated coronary artery lesion risk. Current risk stratification relies on clinical parameters-fever duration or nonspecific inflammatory markers-which fail to capture distinct immunopathological features associated with treatment failure. To bridge this gap, we employed a convergent strategy integrating transcriptomic discovery from two independent cohorts with prospective protein-level and cellular validation in a clinical cohort. Three machine learning models-LASSO regression, Random Forest, and XGBoost-independently identified TREM1 (Triggering Receptor Expressed on Myeloid cells-1) as a core resistance predictor. Prospective validation in 117 KD patients demonstrated that plasma soluble TREM-1 (sTREM-1) was markedly elevated in IVIG-resistant cases (median 1247 vs. 856 pg/mL, P < 0.001) and effectively differentiated KD from other febrile illnesses. Mechanistically, sTREM-1 elevation showed a moderate positive correlation with myeloperoxidase-DNA complexes (ρ = 0.612, P < 0.001), indicating that TREM-1-associated neutrophil hyperactivation is associated with excessive neutrophil extracellular trap (NET) formation and vascular injury. External validation (GSE63881) confirmed TREM1 upregulation (2.1-fold) in resistant patients. Incorporating sTREM-1 into a multivariable prediction model achieved area under curve 0.884 using Firth's penalized logistic regression (optimism-corrected AUC 0.871) in this derivation cohort, significantly outperforming traditional clinical scores. These findings suggest TREM-1-associated NETosis as a potential contributor to the pathobiology of IVIG resistance. As a TRIPOD Type 1b derivation study, external clinical validation in independent multi-center cohorts is required prior to clinical implementation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Heterogeneity in CD40 Ligand Deficiency: Long-term Follow-up of a Patient with the c.156G > A Splice Variant.","authors":"Fayhan Alroqi, Abdulrahman N AlJaber, Nouf Althubaiti, Abeer Al Tuwaijri, Shouq Alzaaqi, Tlili Barhoumi, Abduarahman Almutairi, Bader Almuzzaini, Leena Alsayegh, Maysa Nogoud, Modhi Aljedaie","doi":"10.1007/s10875-026-02019-9","DOIUrl":"https://doi.org/10.1007/s10875-026-02019-9","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen Microarray Reveals Broad and Subclinical Autoimmunity in Patients with Inborn Errors of Immunity.","authors":"Wenjun Zhang, Bijun Sun, Wenjie Wang, Ke Zhu, Qi Wu, Luyao Liu, Chenghao Wang, Feifan Xiao, Qinhua Zhou, Xiaochuan Wang, Jinqiao Sun","doi":"10.1007/s10875-026-02024-y","DOIUrl":"https://doi.org/10.1007/s10875-026-02024-y","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}