Journal of Clinical Immunology最新文献

{"title":"Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program.","authors":"Lea Graafen, Carsten Speckmann, Shahrzad Bakhtiar, Horst V Bernuth, Kai Lehmberg, Peter Bader, Ulrich Baumann, Rita Beier, Stephan Borte, Inken Brockow, E Graham Davies, Maximilian Hartmann, Ursula Holzer, Christian Klemann, Alexandra Y Kreins, Renate Krüger, Udo Kontny, Hans-Jürgen Laws, Andrea Meinhardt, Henner Morbach, Nora Naumann-Bartsch, Tobias Rothoeft, Dominik T Schneider, Andre Willasch, Austen Worth, Markus G Seidel, Michael H Albert, Stephan Ehl, Fabian Hauck, Manfred Hönig, Ansgar Schulz, Catharina Schuetz, Sujal Ghosh","doi":"10.1007/s10875-026-01995-2","DOIUrl":"10.1007/s10875-026-01995-2","url":null,"abstract":"<p><p>TREC-NBS identifies patients with inborn errors of immunity (IEI) and syndromic features, but uncertainty remains regarding their immunological management. To address this, syndromic patients detected by TREC-NBS in Germany between August 2019 and April 2024 were systematically analyzed, including phenotype, treatment, and outcomes. National registries were screened, and data were completed by the treating centres. A total of 77 syndromic patients were identified, with 22 different gene defects found in 72 individuals (93.5%). Primary thymic deficiency was present in 64% (49/77), most commonly due to 22q11.2 deletion syndrome (62%). Common clinical features included congenital heart disease (57%), facial/skeletal abnormalities (53%), and neurological symptoms (36%). Definitive treatments were provided promptly in eligible patients, including 6 thymus transplants and 6 hematopoietic stem cell transplants (HSCT). A watch-and-wait approach was applied to the remaining patients, with 34% (22/65) receiving prophylactic treatment. Recovery of CD3 + T-cell counts was limited to a minority. Overall survival was 89%, with a median follow-up of 32 months (range 0.5-60). To conclude, this is the first comprehensive study of syndromic IEI patients identified through TREC-NBS. The findings show that the German healthcare system enables both early prophylactic care and timely access to definitive therapies. Moving forward, interdisciplinary collaboration will be key to developing evidence-based management guidelines for this challenging patient group.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147457615","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":"Characterisation of a Leaky Splice-Site Mutation Associated with Phenotypic Diversity in Two Unrelated Patients with ARPC1B Deficiency.","authors":"Alex Quach, Jovanka King, Trishni Putty, Michael Gold, Patrick Quinn, Antonio Ferrante","doi":"10.1007/s10875-026-02002-4","DOIUrl":"10.1007/s10875-026-02002-4","url":null,"abstract":"<p><p>Autosomal-recessive pathogenic variants in Actin-related protein 2/3 complex subunit 1B (ARPC1B) result in an inborn error of immunity associated with eczema, thrombocytopenia, leukocytoclastic vasculitis and colitis. ARPC1B deficiency leads to impaired actin filament branching, affecting cytoskeletal processes in leukocytes, including migration, adhesion, endocytosis, and phagocytosis. This report presents two index cases from different families, who despite sharing an identical germline homozygous ARPC1B splice-site variant, ARPC1Bc.64+2T> A, had distinct clinical phenotypes including age of onset of symptoms and clinical manifestations. In addition, differences were observed in their immunological profiles including neutrophil chemotaxis, upregulation of complement receptor expression as well as B cell maturation and responses to EBV transformation. Further molecular investigation suggests the downstream cryptic splice-site activated by the mutation permits ‘leaky splicing’, enabling trace expression of wildtype ARPC1B. This supports a less severe deficiency in ARPC1B activity, rendering a less severe phenotype in one case compared with the other due to differential transcriptional activity of wildtype ARPC1B.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372744","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":"Prognostic Factors for Sideroblastic Anemia with B-cell Immunodeficiency, Periodic Fevers, and Developmental Delay Due to TRNT1 Gene Mutations: A Case Report and Systematic Review.","authors":"Tzu-Hsuan Su, Ni-Chung Lee, Li-Chieh Wang, Bor-Luen Chiang, Hsin-Hui Yu","doi":"10.1007/s10875-026-02000-6","DOIUrl":"10.1007/s10875-026-02000-6","url":null,"abstract":"<p><p>Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD), a rare multisystemic syndrome, occurs due to loss-of-function mutations in the tRNA nucleotidyl transferase 1 (TRNT1) gene. This study reports the case of a 21-month-old female patient with SIFD and compound heterozygous mutations c.824T > A, p.Leu275X (a novel variant) and c.1246 A > G, p.Lys416Glu in TRNT1 gene. The patient had presented with recurrent fever since 10 days of age, along with vasculitis, systemic inflammation with elevated proinflammatory cytokines, decreased B-cell count, and failure to thrive. Furthermore, she did not respond to intravenous immunoglobulin (IVIG) treatment, but her condition stabilized with etanercept (a tumor necrosis factor [TNF] inhibitor) and corticosteroids therapy. In addition, this study includes a systematic review of the clinical presentations, genetic mutations, treatments, and outcomes of 75 patients with SIFD. The estimated 2-, 5-, and 10-year Kaplan–Meier survival probabilities for all patients were 88.45%, 76.67%, 68.84% for all patients; 82.40%, 58.86% and 44.85% for patients with onset age of ≤ 3 months; 70%, 40% and 26.68% for patients with seizures; 88.05%, 66.62% and 59.22% for patients with decreased B cell number; 50% and 33.33% for patients who received hematopoietic stem cell transplantation (HSCT), respectively (log-rank P < 0.05). We concluded that younger age of onset of ≤ 3 months, seizures, and decreased B-cell count are significant poor prognostic factors for survival. Anti-TNF therapy early in life may stabilize patients with autoinflammatory phenotypes; however, the role of HSCT remains controversial.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372768","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 Experience of a Tertiary Reference Center in Central Anatolia with Children Carrying ZAP-70 Variants, Including Two Novel Variants.","authors":"Serdar Göktaş, Ozlem Kalaycik Sengul, Şerife Erdem, Hatice Eke Güngör, Royala Babayeva, Sevgi Bilgic-Eltan, Turan Güzel, Koray Dörterler, Meino Rohlfs, Alper Özcan, Ebru Yilmaz, Musa Karakukcu, Haluk Himmet Akar, Elif Karakoc-Aydiner, Ahmet Özen, Muhsin Elmas, Türkan Patiroğlu, Muhammet E Doğan, Hasan Baş, Naomi Taylor, Safa Baris, Christoph Klein, Ahmet Eken, Ekrem Ünal","doi":"10.1007/s10875-026-01989-0","DOIUrl":"10.1007/s10875-026-01989-0","url":null,"abstract":"<p><p>PURPOSE: Zeta-chain-associated protein kinase 70 (ZAP-70) deficiency, a rare form of combined immunodeficiency (CID), is caused by homozygous or compound heterozygous variants in the ZAP70 gene. ZAP-70, a tyrosine kinase, plays a key role in T-cell receptor (TCR) signaling, which is critical for T cell activation. ZAP-70 deficiency manifests clinically in a variety of ways, including recurring respiratory infections and cutaneous manifestations. METHODS: This study describes the clinical, genetic, and immunological characteristics of four Turkish, two Syrian, and one Azerbaijani patient with ZAP-70 deficiency, including two novel variants. RESULTS: Among seven patients diagnosed with ZAP-70 deficiency, two previously unreported ZAP70 variants were identified. Functional analyses performed in four patients—including three with novel variants—demonstrated impaired TCR-induced proliferation, reduced Interleukin 2 (IL-2) production, and markedly diminished CD8⁺ T cell numbers, supporting the pathogenicity of these variants. Clinical phenotypes were heterogeneous, ranging from severe early-onset infections and cytopenias to autoimmune manifestations and atopy. Notably, even siblings carrying the same variant exhibited divergent immunological profiles and disease severity, highlighting the influence of potential genetic or environmental modifiers. Hematopoietic stem cell transplantation (HSCT) was curative in four patients, while one patient died before transplant. CONCLUSION: This report expands the genetic and phenotypic spectrum of ZAP-70 deficiency by describing two novel variants and emphasizing the value of functional analysis in variant classification and patient management. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365421","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":"Two Cases of CLIPPERS-like Syndrome Sharing a Hypomorphic UNC13D Variant.","authors":"Hirotaka Sagawa, Kosei Hirata, Saori Katayama, Hirofumi Shibata, Etsushi Toyofuku, Shuya Kaneko, Yu Katata, Yusuke Takezawa, Mitsugu Uematsu, Iichiroh Onishi, Yuto Yamazaki, Takaaki Hattori, Masahide Yamamoto, Masaki Shimizu, Kohsuke Imai, Takahiro Yasumi, Tomohiro Morio, Takanori Yokota, Yoji Sasahara, Hirokazu Kanegane","doi":"10.1007/s10875-026-01988-1","DOIUrl":"10.1007/s10875-026-01988-1","url":null,"abstract":"<p><p>Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a central nervous system (CNS) inflammatory disease characterized by contrast-enhanced MRI findings of salt-and-pepper-like lesions predominantly affecting the brainstem and cerebellum. We report two patients with CLIPPERS-like brain MRI findings who carried the same missense UNC13D variant in one allele along with deleterious variants in the opposite allele. Patient 1, a 23-year-old female, presented at 15 years of age with neurological symptoms and an MRI showing spontaneously resolving, contrast-enhancing lesions in the cerebellum. At age 16, the patient experienced an episode with systemic manifestations followed by recurrent CNS lesions that responded to steroid therapy. At age 22, the patient developed punctate to nodular contrast-enhancing lesions in the brainstem, cerebellum, and cerebrum, findings consistent with CLIPPERS. Patient 2, an 18-year-old female, presented at age 11 with ataxia and dysarthria, and an MRI showing multiple contrast-enhancing lesions in the cerebellum and brainstem, consistent with CLIPPERS MRI findings. Cerebellar biopsy revealed perivascular CD4+ T-lymphocyte infiltration, and the patient responded to steroid therapy, leading to an initial diagnosis of CLIPPERS. These patients were suspected of having inborn errors of immunity and were identified to have compound heterozygous UNC13D variants along with downregulated Munc13-4 protein. Both patients underwent allogeneic hematopoietic cell transplantation, with patient 1 remaining neurologically stable for two years post-transplantation, while patient 2 experienced a post-transplant relapse requiring steroid therapy. These cases highlight that biallelic variants in the UNC13D gene may cause CNS-predominant inflammation that mimics CLIPPERS.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355208","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":"Unraveling BCR Repertoire Diversity and its Impact on Glucocorticoid Therapy in Pediatric Idiopathic Nephrotic Syndrome.","authors":"Yeping Luo, Chan Zou, Xinjie Yu, Chengxian Guo, Hongmei Dai, Jie Huang, Mai Xun, Cuirong Duan, Song Li, Zhihui Li, Guoping Yang","doi":"10.1007/s10875-026-01994-3","DOIUrl":"10.1007/s10875-026-01994-3","url":null,"abstract":"<p><p>AIM: Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children, but its underlying mechanisms remain unclear. Although glucocorticoids (GC) are the first-line treatment, approximately 10% of INS cases are steroid-resistant (SRNS), and 50% may progress to refractory nephrotic syndrome (RNS). B cells play a crucial role in INS pathogenesis, treatment, and prognosis. This study aims to explore B-cell receptor repertoire (BCRR) characteristics in INS patients to identify molecular signatures associated with disease outcomes and develop early risk prediction models for RNS and SRNS. METHODS: A case-control study was conducted using peripheral blood samples from 40 initial diagnosed INS patients and 56 age-matched healthy controls. BCRR was sequenced using dimer-avoided multiplex PCR, followed by Illumina NovaSeq sequencing. Immunoglobulin heavy chain (IGH) sequences were mapped and analyzed for diversity, clone expansion and shared clone, isotype usage, class-switch recombination (CSR), IGHV/J gene usage, CDR3 length and somatic hypermutation (SHM). Additionally, a prospective cohort study was conducted on INS patients, with BCRR measured at baseline and follow-up to track changes in response to treatment. Longitudinal analysis was performed to identify specific B-cell clones and predict treatment resistance. RESULTS: The BCRR of INS patients exhibited lower evenness compared to controls, with significant increases in the usage of IGHM/D mutated and IgE/IgG12 isotypes. Public B-cell clones, including five specific CDR3 amino acid sequences, were identified across INS patients. NRNS patients showed increased clonal expansion with specific CDR3 sequences characters on IGHV5-51_IGHJ6 sequences and shorter CDR3 lengths, suggesting strong and focused autoimmune responses. In contrast, RNS and SRNS patients exhibited enhanced IgE-mediated immune responses, characterized by increased IgE BCRR diversity, decreased evenness and increased CSR. Early prediction models were developed based on BCRR parameters, successfully distinguishing between RNS and NRNS, SRNS and SSNS patients. CONCLUSION: B-cell-mediated humoral immunity plays a pivotal role in INS pathogenesis, with distinct immune profiles associated with clinical outcomes. Non- refractory nephrotic syndrome (NRNS) patients exhibit clonal expansion with antigen-driven immune responses, whereas SRNS and RNS patients demonstrate persistent IgE-mediated responses that are resistant to GC but sensitive to second-line immunosuppressants. These findings offer new insights into the mechanisms of steroid resistance and provide a basis for early diagnosis and personalized treatment strategies in INS. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344481","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":"Porto-sinusoidal Vascular Disease is Associated with Gastrointestinal Disorders in Common Variable Immunodefiency.","authors":"Emilie Corvilain, Laurence Gérard, Jehane Fadlallah, Lionel Galicier, Laure Delaval, Jessy Alchidiac, Aurélie Plessier, David Boutboul, Claire Fieschi, Eric Oksenhendler, Pierre Emmanuel Rautou, Marion Malphettes","doi":"10.1007/s10875-026-01985-4","DOIUrl":"10.1007/s10875-026-01985-4","url":null,"abstract":"<p><p>PURPOSE: We aimed to describe porto-sinusoidal vascular disease (PSVD) in a large cohort of predominantly antibody deficiency (PAD) patients and sought to identify contributing factors for PSVD development by comparing CVID patients with and without PSVD. METHOD: Patients were retrospectively identified from a national database. RESULTS: Sixty-eight of 386 PAD patients, including 63 of 267 CVID patients were diagnosed with PSVD. Median time from PAD to PSVD diagnosis was 9.2 years (interquartile range, 4.6–14.5). CVID patients with late onset combined immunodeficiency and non-infectious complications were overrepresented among PSVD patients (37.5% and 87.3%, respectively). Nodular regenerative hyperplasia (NRH) was the most common finding on liver biopsy (79%), alongside with intra-sinusoidal CD8+ T-cell infiltration (65.7%). In an adjusted multivariate model, gastro-intestinal (GI) complications (adjusted odds ratio, 4.94; 95% CI, 1.91–12.79; p = 0.001) and low naive CD4+ T-cell count (p = 0.001) were strongly associated with the occurrence of PSVD in CVID patients, together with low serum IgA level (p = 0.018) and lymphoproliferation (p = 0.027). GI complications were observed in 90.5% of PSVD patients, preceding PSVD diagnosis in 84% of them by a median duration of 10.7 years. The 20-year probability to develop PSVD after CVID diagnosis was estimated at 38.7% (95% CI, 30.1–48.7) and 11.7% (95% CI, 5.0–26.0) in patients with or without GI complications, respectively (p < 0.001). The median overall survival from onset of PSVD was 8.4 years. CONCLUSION: Our data suggest that impaired intestinal barrier in a context of T-cell defect may play a key role in the development of PSVD in CVID patients. Whether complete control of GI complications would prevent the occurrence of PSVD remains to be evaluated. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317161","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":"Primary Immunodeficiency Diseases with BCG-Induced Diseases: A 15-Year Longitudinal Cohort Study.","authors":"Lu Xia, Yang Yang, Xue-Ying Li, Ping Liu, Xiao-Min Wang, Zhen Huang, Shui-Hua Lu, Xu-Hui Liu","doi":"10.1007/s10875-026-01996-1","DOIUrl":"10.1007/s10875-026-01996-1","url":null,"abstract":"<p><p>BACKGROUNDS: Children with primary immunodeficiency (PID) may develop severe infections after BCG vaccination. There is limited information on the long-term prognosis and management of these BCG-induced diseases. METHODS: Data were gathered from a cohort study on BCG-induced diseases at the Shanghai Public Health Clinical Center, spanning from January 2007 to August 2022. The study enrolled patients with confirmed PIDs, and information was obtained via personal interviews with patients or their guardians, as well as from their medical records. This allowed us to gather clinical and genetic details, treatment history, and the outcomes of their PIDs. We evaluated antimycobacterial outcomes and analyzed the impact of HSCT and IFN-γ therapy on the risk of death. RESULTS: Out of 422 patients with BCG-induced diseases, 109 patients with confirmed PID were included in the analysis. Of these, 88.1% had developed distant or disseminated BCG infection, and the median duration of illness documented in the study was 57 months (IQR 31–79). The three most common PIDs in this cohort were MSMD (47/109, 43.1%), CGD (28/109, 25.7%), and CID (19/109 or 17.4%). The estimated five-year and ten-year survival rates were 80.3% (95%CI, 72.1%-88.5%) and 69.3% (95%CI, 56.8%-81.8%). Patients who received hematopoietic stem cell transplantation therapy (HSCT) had a significantly higher success rate with antimycobacterial treatment (75.8% vs. 0%). The survival benefit of HSCT varies across immunodeficiency types but is clearly beneficial for CID (p < 0.001). IFN-γ therapy presented no significant effect on the survival of CGD and MSMD. The initial STRONGkids nutritional score (HR = 2.27 per point, 95%CI 1.65–3.13) and gender (HR for male = 4.89, CI 1.36–17.57) are significant predictors of survival. Mutations in 6 genes (IL12RB1, CYBB, IFNGR1, IL2RG, STAT1, and RAG1) account for 66% of BCG-associated immunodeficiency mutations. CONCLUSIONS: PID complicated by BCG infection may cause persistent and severe conditions. Patients with severe nutritional risk in the early stages of infection have a higher risk of death and should prioritize HSCT. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306350","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":"Fatal Systemic Granulomatous Disease Associated with Vaccine-Derived Rubella Virus in AIOLOS-Associated Immunodeficiency.","authors":"Linda Zhou, Hye Sun Kuehn, Dayna Gager, Agustin A Gil Silva, Ludmila M Perelygina, LiJuan Hao, Min-Hsin Chen, Julie E Niemela, Jennifer L Stoddard, Matthew Helm, Karolyn Wanat, Kathleen Sullivan, Galen Foulke, Thomas H Leung, Sergio D Rosenzweig, Misha Rosenbach","doi":"10.1007/s10875-026-01990-7","DOIUrl":"10.1007/s10875-026-01990-7","url":null,"abstract":"<p><p>We present a case of disseminated granulomatous disease associated with live attenuated vaccine-derived rubella virus (VDRV) in an immunodeficient patient who subsequently developed fatal multi-organ failure, including neurological deficits, with VDRV detected in the cerebrospinal fluid. Posthumous genetic analysis found a heterozygous missense mutation in IKZF3, a gene where haploinsufficiency is linked to immunodeficiency and immune dysregulation. Functional studies demonstrated that this mutation decreases AIOLOS protein stability and half-life, and family members carrying the same mutation exhibited decreased AIOLOS levels. This report underscores the importance of considering persistent rubella virus (RuV) infection in patients with cutaneous granulomatous lesions and highlights the need for comprehensive evaluation to uncover potential underlying immunodeficiencies, which could inform and optimize individualized treatment strategies.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288995","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":"TFRC Germline Variants and Inborn Error of Immunity: Mechanistic Insights into Iron-Immune Crosstalk.","authors":"Amal H Aljohani","doi":"10.1007/s10875-026-01999-y","DOIUrl":"10.1007/s10875-026-01999-y","url":null,"abstract":"<p><p>Mutations in TFRC, which encodes transferrin receptor 1 (TfR1/CD71), have emerged as a rare but significant cause of inborn error of immunity (IEI). TfR1 is a crucial membrane glycoprotein responsible for receptor-mediated iron uptake, playing fundamental roles in erythropoiesis and immune function, and linking impaired iron homeostasis to profound immune dysfunction. Notably, TFRC deficiency provides a biologically instructive human model demonstrating that iron uptake via TfR1 is a non-redundant metabolic and signaling checkpoint required for antigen receptor–driven immune activation, clonal expansion, and immune homeostasis. This review summarizes the molecular mechanisms of TfR1, including its interactions with transferrin, and explores how pathogenic TFRC mutations impair iron uptake, affect immune cells, lymphocyte activation, and clonal diversity. We also examine TfR1 in the context of immunodeficiency, linking its roles in iron metabolism and immune regulation to clinical outcomes. By integrating current knowledge on TfR1 biology, molecular mechanisms with patients’ clinical presentation, observations, variants, and therapeutic approaches, this review highlights knowledge gaps and unresolved questions, providing a framework for future research toward elucidating TfR1 mechanisms, improving patient diagnosis, and ultimately enabling the development of targeted therapies for TfR1-mediated immunodeficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227074","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}