Journal of Clinical Immunology最新文献

{"title":"Hypoproteinemia and Hypogammaglobulinemia Due to a Homozygous FCGRT Mutation.","authors":"Abdul Samet Ala, Bernice Lo, Ahmet Ozen, Ali Islek, Gokhan Tumgor","doi":"10.1007/s10875-026-02032-y","DOIUrl":"10.1007/s10875-026-02032-y","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205104","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":"Novel Partial Loss-of-function STAT3-variant as Cause of Hyper-IgE-Syndrome in a Danish Family with Variable Expressivity.","authors":"Camilla Heldbjerg Drabe, Jonathan Gehrig, Jens Magnus Bernth Jensen, Mira Marie Laustsen, Carsten Schade Larsen, Camilla Darum Sørensen, Kirstine Overgaard Dyrmose, Sophia Hammer-Hansen, Jens Wittner, Tania Masmas, Hanne Marquart, Stephan Ehl, Line Borgwardt, Terese L Katzenstein","doi":"10.1007/s10875-026-02036-8","DOIUrl":"10.1007/s10875-026-02036-8","url":null,"abstract":"<p><p>A novel heterozygous missense variant in STAT3 (NM_139276.3: c.1250G > C, NP_644805.1: p.(Arg417Thr) was identified in a Danish family spanning five generations with diverse phenotypes consistent with autosomal dominant STAT3-Hyper-IgE-Syndrome (STAT3-HIES). Genetic analysis confirmed the absence of the variant in population databases, and computational predictions of pathogenicity were conflicting. Functional assessment revealed that the variant STAT3 Arg417Thr maintained normal DNA binding but exhibited reduced IL-6-induced transcriptional activity and no negative-dominance. Further, significantly impaired STAT3-dependent, IL-10-mediated suppression of TNF-α production were found in patient-derived monocytes, consistent with a partial loss-of-function effect. Clinically, affected individuals presented with recurrent staphylococcal skin abscesses, eczema, atopic or infectious complications, and characteristic facial features. There was a marked variability in extra-hematopoietic manifestations such as retained primary teeth, vascular anomalies, and psychiatric disorders. Laboratory findings included elevated serum IgE levels, but only slightly reduced or normal Th17 cell counts. NIH-HIES scores varied within the family (range: 12-34), highlighting the variability of clinical expression. Based on ACMG guidelines, the variant was classified as likely pathogenic due to absence from controls, co-segregation with disease, and supportive functional evidence. This report highlights the challenges in interpreting novel STAT3 variants and the critical need for functional validation in uncertain cases. The findings emphasize the importance of molecular diagnosis irrespective of clinical scoring and address the ethical complexities of genetic testing in familial disease.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199167","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":"Retrieval-Augmented Language Models for Clinical Decision Support in the Classification of Inborn Errors of Immunity.","authors":"Afrooz Arzehgar, Saeed Varasteh Yazdi, Hamid Ahanchian, Saeid Eslami","doi":"10.1007/s10875-026-02035-9","DOIUrl":"10.1007/s10875-026-02035-9","url":null,"abstract":"<p><p>Early diagnosis of inborn errors of immunity (IEIs) can make a difference in patient outcomes and even cut healthcare costs. However, there are some challenges to overcome, such as clinical complexity, low awareness, and limited resources. Generative artificial intelligence has attracted considerable global attention in medical domains, particularly when integrated into clinical decision support systems (CDSS), as it has the potential to facilitate data interpretation, clinical reasoning, and the optimal use of knowledge resources. Preliminary studies have explored the potential of large language models (LLMs) in various information retrieval tasks, but a systematic evaluation of LLMs with and without retrieval mechanisms for IEI classification is still unexplored. We evaluated and compared the validity and reliability of the responses generated by four open-source and closed-source LLMs, in their baseline form and with augmented data, across 169 IEI patient records, using two input scenarios and four prompt templates. Our primary finding was that the models varied in terms of reliability and performance. The most reliable models were Gemini-1.5-Pro and Llama-3.1-8B-Instruct ([Formula: see text]) and the best-performing model without data augmentation was Gemini with an F1 score of [Formula: see text]. The results also showed that retrieval strategies improved the average classification performance, increasing the F1 score from [Formula: see text] to [Formula: see text] across all models. DeepSeek-R1, which reasoned over retrieved information through the integration of quality refinement and structured retrieval, achieved the best weighted F1 score of [Formula: see text]. The study highlights the effective use of generative AI and retrieval-augmented models as a decision support tool for IEI classification. However, incorporating retrieval systems into clinical decision-making processes requires adequate input, effective prompt engineering, and the adoption of retrieval strategies.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163316","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":"Clinical Cognition and Practice in Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome.","authors":"Siqiao Liang, Xuemei Huang, Xiaona Liang, Siyao Wu, Yan Ning, Ni Chen, Limei Hong, Zengtao Luo, Xiaoshan Wei, Quanfang Chen, Jingmin Deng, Meihua Li, Meiling Yang, Wen Zeng, Ping Yan, Hongyu Wei, Jiujin Zhang, Fu Cao, Xinxin Zhong, Zhen Wei, Qing Wei, Ming Jiang, Chengqiong Xu, Ting Chen, Shilian Liang, Xiayan Meng, Chunhai Qin, Dongming Qu, Lanke Zou, Yinghua Li, Zhiyi He","doi":"10.1007/s10875-026-02039-5","DOIUrl":"10.1007/s10875-026-02039-5","url":null,"abstract":"<p><p>Adult-onset immunodeficiency syndrome mediated by anti-interferon-gamma autoantibody (AIGA) is a rare disorder that has garnered increasing recognition in recent years. The condition is most prevalent among adults in Southeast Asia. It is characterized by recurrent disseminated opportunistic infections, frequently involving multiple organ systems such as the lungs, lymph nodes, bones, and skin. The pathogenesis is primarily attributed to the presence of neutralizing AIGAs, which impair the IFN-γ-mediated JAK-STAT1 signaling pathway, leading to compromised host defense against intracellular pathogens. Laboratory diagnosis requires both quantification of AIGA titers and assessment of their neutralizing activity. Clinical diagnosis relies on a combination of characteristic manifestations, demonstrated immunologic dysfunction, and seropositivity for AIGAs. During the acute stage, management focuses on antimicrobial therapy, while during the stable stage, it can be categorized into three clinical subtypes: high AIGA titers with immune damage, high AIGA titers without immune damage, and low AIGA titers without immune damage. Among these, patients with high AIGA titers and immune damage require immunomodulatory strategies-such as glucocorticoids and rituximab-tailored to individual AIGA levels and immune status. Due to the current absence of unified clinical guidelines, this review synthesizes available evidence and clinical expertise to provide a comprehensive overview of the epidemiology, pathogenesis, clinical presentation, diagnostic criteria, and treatment approaches related to AIGA-mediated immunodeficiency. Our aim is to assist clinicians in the recognition and management of this syndrome and to facilitate further clinical research and guideline development.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150026","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":"FXII Frameshift Variant Does Not Cause Hereditary Angioedema with Normal C1 Inhibitor.","authors":"Toshiyuki Miyata, Takahiko Horiuchi, Michihiro Hide","doi":"10.1007/s10875-026-02041-x","DOIUrl":"10.1007/s10875-026-02041-x","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13226351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138236","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 Novel MSN Mutation Impairs CD4⁺ T cell Differentiation and Drives Autoantibody Production.","authors":"Ke Zhu, Bijun Sun, Wenjun Zhang, Luyao Liu, Wenjie Wang, Chenghao Wang, Feifan Xiao, Qinhua Zhou, Xiaochuan Wang, Jinqiao Sun","doi":"10.1007/s10875-026-02034-w","DOIUrl":"10.1007/s10875-026-02034-w","url":null,"abstract":"<p><strong>Purpose: </strong>To report a patient with a novel MSN mutation causing X-linked moesin-associated immunodeficiency (X-MAID) and investigate its pathogenic mechanisms.</p><p><strong>Methods: </strong>Clinical and immunological data of the patient were collected. Autoantibody levels were measured using antigen microarrays. Whole-exome sequencing was performed to identify gene mutations. The stability of the mutant MSN protein was analyzed via transient transfection and cycloheximide chase assay in HEK293T cells. MSN protein expression, immunophenotyping, and T cell activation and apoptosis were assessed by flow cytometry.</p><p><strong>Results: </strong>The patient was a 2-year-old boy, presented with recurrent infections, Kawasaki disease, and early-onset broad-spectrum autoantibody production. A novel hemizygous MSN mutation (c.344T > C, p.I115T) was identified in the patient. The MSN p.I115T mutant showed reduced protein stability and decreased expression in multiple immune cell types. Immunophenotyping revealed follicular regulatory T (Tfr) cell reduction, Th1/Th17 imbalance, enhanced CD4⁺ T cell activation and proliferation, and impaired B cell maturation.</p><p><strong>Conclusion: </strong>We report a novel MSN mutation associated with recurrent infections, early-onset broad-spectrum autoantibody production, and Kawasaki disease. MSN deficiency may contribute to autoimmunity through Tfr cell reduction and Th1/Th17 imbalance.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005409","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":"Autoimmune Retinopathy Complicating TLR7-related Monogenic Interferonopathy.","authors":"Alessio Antropoli, Maria Vittoria Cicinelli, Edoardo Balduzzi, Lorenzo Bianco, Elisabetta Martina, Marco Zecca, Francesco Bandello, Elisabetta Miserocchi","doi":"10.1007/s10875-026-02033-x","DOIUrl":"10.1007/s10875-026-02033-x","url":null,"abstract":"<p><p>Gain-of-function variants in the TLR7 gene have been associated with a spectrum of clinical manifestations, including systemic lupus erythematosus (SLE)-like disease, neuromyelitis optica, and progressive leukoencephalopathy. The p.(Leu528Ile) variant has previously been shown to underlie this constellation of findings. Here, we report the extended follow-up of a previously described young female patient with TLR7-related interferonopathy, who developed non-paraneoplastic autoimmune retinopathy following a failed attempt to taper her systemic immunomodulatory therapy. This case expands the phenotypic spectrum of TLR7-related disease and highlights a potential link between interferon-driven immune dysregulation and autoimmune retinal pathology.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972870","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":"Genetic Diagnosis and Identification of a Novel De Novo RELA Variant in Familial Behçet-like Autoinflammatory Syndrome Type 3: A Case Report.","authors":"Ting Zhang, Zhou Zhou, Weimiao Li, Yongkang Chen, Hai Tang, Dongmei Zhou","doi":"10.1007/s10875-026-02026-w","DOIUrl":"10.1007/s10875-026-02026-w","url":null,"abstract":"<p><strong>Objective: </strong>To perform genetic diagnosis and pedigree analysis in a case of autosomal dominant Familial Behçet-like Autoinflammatory Syndrome type 3 (AIFBL3) caused by a novel RELA variant.</p><p><strong>Methods: </strong>Peripheral blood samples collected from the proband and parents underwent conventional genetic screening, next-generation sequencing (NGS), and Sanger sequencing for familial validation.</p><p><strong>Results: </strong>A de novo heterozygous RELA variant (NM_021975.4:c.539 C > T, p.Ser180Phe) was identified in the proband. Parental testing confirmed its de novo origin.</p><p><strong>Conclusion: </strong>The RELA c.539 C > T variant was classified as likely pathogenic for AIFBL3, providing a basis for genetic counseling. In future pregnancies, prenatal diagnosis through targeted familial mutation analysis could be offered to this family to inform reproductive decision-making.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972819","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":"Reticular Dysgenesis in an Extremely Low Birth Weight Infant: A Case Report.","authors":"Kaoru Kinoshita, Hideki Muramatsu, Manabu Wakamatsu, Kazuto Ueda, Yoshiaki Sato, Yoshiyuki Takahashi","doi":"10.1007/s10875-026-02029-7","DOIUrl":"10.1007/s10875-026-02029-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13175993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941653","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":"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":"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":4.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328136/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}