Journal of Clinical Immunology最新文献

{"title":"A Novel Compound Heterozygous Mutation in the IL12RB1 Gene Causes Susceptibility To Mycobacterium Tilburgii Infection.","authors":"Mengqing Qian, Jingyu Zhou, Peidong Chen, Ning Jiang, Ting Wang, Xinchang Chen, Haoxin Xu, Feiran Zhou, Yixuan Yang, Xing Lin, Qingluan Yang, Lingyun Shao, Qiaoling Ruan, Wenhong Zhang","doi":"10.1007/s10875-025-01930-x","DOIUrl":"10.1007/s10875-025-01930-x","url":null,"abstract":"<p><p>Mendelian susceptibility to mycobacterial disease (MSMD) is a rare clinical syndrome that is characterized by selective vulnerability to intracellular pathogens. Deficiency in IL12RB1 is the most common type of MSMD but the heterogeneity of its clinical Manifestation Makes precise diagnosis difficult. Here, we report a previously healthy 29 year-old woman who had suffered from disseminated infection with Mycobacterium tilburgii, which is a rare, unculturable environmental mycobacteria, for over 2 years. We used whole exome sequencing to detect a novel compound heterozygous variant in the IL12RB1 gene. Immunological analysis of the patient's peripheral lymphocytes showed a barely detectable level of IL-12Rβ1, a reduced population of follicular helper T (Tfh) cells and impaired production of IFN-γ in response to IL-12/IL-23 stimulation. Metagenomic next-generation sequencing was used to identify the causative pathogen and to analyze drug susceptibility. The infection was contained by a combination of anti-mycobacterial drugs and IFN-γ supplementary treatment. An RNA-seq analysis, using follow-up blood samples, revealed the limited success of these treatments over 6 months. Our findings support the screening for inherited immunological problems in patients with difficult-to-treat mycobacterial infections. The suboptimal response to prolonged anti-mycobacterial drugs and IFN-γ supplementation warrants the development of novel therapeutic strategies for MSMD patients.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"133"},"PeriodicalIF":5.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199683","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":"Malignancy and Autoimmune Susceptibility in Adult Patients with Human Inborn Errors of Immunity.","authors":"Alejandro Segura-Tudela, Celia Nieto-López, Francisco Javier Bermejo-Olivera, Luis A Andara, Javier Arroyo-Ródenas, Lucía Dueñas-Prieto, Ángel Alfocea-Molina, Estela Paz-Artal, Daniel Pleguezuelo, Oscar Cabrera-Marante, Luis M Allende","doi":"10.1007/s10875-025-01935-6","DOIUrl":"10.1007/s10875-025-01935-6","url":null,"abstract":"<p><p>Inborn errors of immunity (IEI) are a heterogeneous group of genetic disorders that disrupt the normal development and function of the immune system. These diseases not only increase susceptibility to infections but also significantly elevate the risk of developing malignancies and autoimmune diseases. The interplay between immune dysregulation, chronic inflammation, and altered cellular homeostasis in IEI can lead to aberrant cellular proliferation and self-reactive immune responses. Malignancy in IEI often arises due to the immune system's failure to effectively eliminate transformed cells, predisposing patients to lymphomas, leukemias and solid tumors. Autoimmune diseases in IEI can result from defective T-regulatory cell function, impaired central or peripheral tolerance mechanisms or B-cell dysregulation leading to autoantibody production. This work was a retrospective study of 173 adults with IEI suspicion who underwent genetic sequencing between 2005 and 2023. A significant increase of malignancies was observed in patients with a molecular diagnosis (w_MolDx) compared to those without (wo_MolDx). Notably, hematologic malignancies were predominant in the w_MolDx cohort, whereas solid tumors were more frequently observed in the wo_MolDx group. In contrast, the correlation between autoimmune diseases and molecular diagnosis was less evident when comparing w_MolDx and wo_MolDx patients. Understanding the complex relationship between IEI, malignancies and autoimmunity is crucial for optimizing patient management. Early diagnosis of IEI allows for timely interventions, including hematopoietic stem cell transplantation, gene therapy and targeted immunomodulatory therapies, which can mitigate the risk of both malignancies and autoimmune complications.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"136"},"PeriodicalIF":5.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199746","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":"Diagnostic and Monitoring Strategies for VEXAS Syndrome: Evaluating Sanger Sequencing, NGS, and the SWIM-Score.","authors":"Lasse von Bornemann Fløe, Kirstine Overgaard Dyrmose, Camilla Darum Sørensen, Maja Nørgaard, Fie Kirstine Udby Pedersen, Johan Vad-Nielsen, Michael Knudsen, Mette Christiansen, Marie Bill, Mads Nyhuus Bendix Rasch, Ellen Margrethe Hauge, Anne Troldborg, Nicklas Heine Staunstrup, Jens Magnus Bernth Jensen","doi":"10.1007/s10875-025-01932-9","DOIUrl":"10.1007/s10875-025-01932-9","url":null,"abstract":"<p><p>VEXAS syndrome is an adult-onset autoinflammatory disorder caused by somatic UBA1 variants, but there are no standardized criteria for genetic testing or diagnostics. This study compared Sanger sequencing and next-generation sequencing (NGS) for detecting UBA1 variants in patients with suspected VEXAS, assessed the ability of Sanger sequencing to estimate variant allele fractions (VAFs), and evaluated the Maeda et al. scoring system for selecting patients for genetic testing in a primary cohort and a validation cohort. In the primary cohort of 104 patients, Sanger sequencing identified VEXAS variants in 12%, with no additional cases detected by NGS. Sanger sequencing accurately quantified VAFs ranging from 0.1 to 0.9. In a small longitudinal subset (n = 3), VAFs in blood correlated with CRP levels, increased over time despite various treatments, but decreased in two patients after initiation of Azacitidine treatment. The novel parameters, VAF in myeloid cells and VEXAS cell concentration, showed promise as exploratory markers for patient monitoring. The Maeda-score, requiring a threshold score of 2 for 100% sensitivity, exhibited low specificity-29% in the primary cohort and 41% in the validation cohort (n = 62, with 2 carrying VEXAS variants). In contrast, the simplified SWIM-score-based on Skin involvement, Weight loss, Inflammation, and Macrocytic anemia-achieved 100% sensitivity in both cohorts, with higher specificities of 47% and 65%, respectively. In conclusion, Sanger sequencing reliably detected UBA1 variants and quantified VAFs. Monitoring VAF and VEXAS cell concentration may track disease progression, and the SWIM-score demonstrated potential for accurately selecting patients for UBA1 testing.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"138"},"PeriodicalIF":5.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199687","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":"Malignancy in Adults with Inborn Errors of Immunity: A Retrospective Single-Center Study.","authors":"Reyhan Gumusburun, Onurcan Yıldırım, Metehan Karakoc, Kasım Okan, Sinem Inan, Ceyda Tunakan Dalgıc, Hatice Serpil Akten, Gulhan Bogatekin, Gokten Bulut, Meryem Demir, Hasibe Aytac, Asuman Camyar, Melih Ozısık, Derya Demir, Nur Soyer, Mehmet Soylu, Funda Elmas Uysal, Ayca Aykut, Asude Durmaz, Semiha Ozgul, Aytul Zerrin Sin, Omur Ardeniz","doi":"10.1007/s10875-025-01910-1","DOIUrl":"10.1007/s10875-025-01910-1","url":null,"abstract":"<p><strong>Purpose: </strong>Inborn Errors of Immunity (IEI) often lead to recurrent infections, immune dysregulation, and an increased risk of malignancies. Due to the heterogeneity in IEI presentations, personalized monitoring is essential for early detection of non-infectious complications. This study aims to document the characteristics and prevalence of malignancies in IEI patients.</p><p><strong>Methods: </strong>A retrospective review of 355 patients diagnosed with IEI at the Adult Allergy and Immunology Clinic of Ege University was conducted. Data on demographics, clinical presentations, laboratory results, and immunological and genetic profiles of patients with malignancies were analyzed.  RESULTS: A total of 40 patients with neoplasia (F/M: 18/22; median age: 51.58 years, range: 18-91) were evaluated. The median ages at IEI symptom onset, diagnosis, and neoplasm diagnosis were 16.5, 45, and 39.5 years, respectively. Malignancy was diagnosed in 60% of patients before IEI, with referrals for low immunoglobulin levels and/or severe infections, and for a genetic profile suggestive of immunodeficiency. The prevalence of malignancy in the overall cohort was 10.42% (37/355), while it was significantly higher in the common variable immunodeficiency (CVID) subgroup, reaching 20.44% (28/137). Lymphoma was the most common malignancy at 45.9%, primarily non-Hodgkin lymphoma (NHL) at 40.5%, with diffuse large B-cell lymphoma (DLBCL) as a key subtype; carcinomas were the second most common at 35.1%. Hematologic malignancies were significantly more frequent among patients with CVID (90.5%), whereas non-hematologic malignancies predominated in the non-CVID group (77.8%) (p = 0.024). Lymphoproliferation was more common in hematologic malignancies (85.7%) compared to non-hematologic malignancies (25.0%) (p < 0.001). Genetic variants were identified in 61% of cases, with 37% classified as pathogenic or likely pathogenic, including variants in TNFRSF13B/TACI, CCDC40, PLCG2, ATM, CARD11, CHEK2, CNV, COPB1, HPS5, LYST, MAPK8IP1, NBS1, NF1, NFKBIA, PI4KA, POLE, SPI1, and TAP2.</p><p><strong>Conclusions: </strong>Findings confirm that NHL, particularly DLBCL, is the most prevalent malignancy in this cohort. Given the link between malignancies and underlying IEI, immunologic evaluation is recommended, particularly for NHL patients. The observed predominance of hematologic malignancies among CVID patients and the association with lymphoproliferation further emphasize the need for heightened malignancy surveillance and early immunologic workup in this subgroup. Further research on biomarkers for malignancy prediction in IEI is warranted.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"128"},"PeriodicalIF":5.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137757","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":"Common Variable Immunodeficiency Disorder: A Decade of Insights from a Cohort of 150 Patients in India and the Use of Machine Learning Algorithms to Predict Severity.","authors":"Umair Ahmed Bargir, Priyanka Setia, Mukesh Desai, Chandrakala S, Aparna Dalvi, Shweta Shinde, Maya Gupta, Neha Jodhawat, Amrutha Jose, Mayuri Goriwale, Reetika Malik Yadav, Disha Vedpathak, Lavina Temkar, Snehal Shabrish, Gouri Hule, Vijaya Gowri, Prasad Taur, Amita Athavale, Farah Jijina, Shobna Bhatia, Akash Shukla, Manas Kalra, Meena Sivasankaran, Sarath Balaji, Punit Jain, Sujata Sharma, Harikrishnan Gangadharan, Gaurav Narula, Ratna Sharma, Pranoti Kini, Mamta Mangalani, Abhishek Zanwar, Himanshi Chaudhary, Narendra Kumar Chaudhary, Ujjawal Khurana, Ashish Bavdekar, Girish Subramaniam, Revathi Raj, Subhaprakash Saniyal, Nitin Shah, Tehsin Petiwala, Prawin Kumar, Venkatesh Pai, Sagar Bhattad, Abhinav Sengupta, Manish Soneja, Dayanand Upase, Abhijeet Ganapule, Indrani Talukdar, Manisha Madkaikar","doi":"10.1007/s10875-025-01897-9","DOIUrl":"https://doi.org/10.1007/s10875-025-01897-9","url":null,"abstract":"<p><p>Common Variable Immunodeficiency (CVID) is a heterogeneous disorder characterized by impaired antibody production and recurrent infections. In this study we investigated the clinical and immunological features of CVID in Indian patients and develops a machine learning model for predicting disease severity. We retrospectively analyzed 150 patients diagnosed with CVID over a decade at a tertiary care center in India. The median age of diagnosis was 18 years, with a male predominance (62%). The majority of patients (66.6%) had a severe phenotype, with recurrent respiratory tract infections being the most common clinical manifestation (84.2%). Gastrointestinal complications were observed in 45% of patients, while autoimmune manifestations were seen in 21%. All patients exhibited hypogammaglobulinemia. IgA levels varied, with 7.8% normal and 14.5% undetectable. IgM levels were decreased in 85.5% of patients. B-cell analysis revealed 64.4% had reduced class-switched memory B cells, with 21.7% showing very low levels. Nine adult patients presented with late-onset combined immunodeficiency. Genetic testing, performed on 52 patients, identified underlying monogenic causes in 29 pediatric and 15 adult patients. LRBA deficiency was the most common genetic defect, found in seven pediatric and three adult patients. We developed a novel machine learning-based severity prediction model for CVID patients, utilizing readily available lymphocyte subsets, class-switched memory B cell counts, and serum immunoglobulin levels to provide an accessible and robust tool for predicting disease severity using Ameratunga's clinical severity score. Random Forest outperformed other models across all metrics, achieving an accuracy of 0.853 (95% CI: 0.840-0.866). Feature importance analysis across all models identified Th-Tc ratio, CD19, and IgM levels as the most influential predictors for severity prediction. Our study highlights the diverse clinical and immunological features of CVID in Indian patients, emphasizing the need for early diagnosis and individualized management strategies. The machine learning model developed using commonly available immune parameters provide a robust tool for predicting disease severity, potentially guiding treatment strategies to improve patient outcomes.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"127"},"PeriodicalIF":5.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956147","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":"To The Editor a Novel Mutation in MALT1 Deficiency.","authors":"Hulya Kose","doi":"10.1007/s10875-025-01924-9","DOIUrl":"https://doi.org/10.1007/s10875-025-01924-9","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"126"},"PeriodicalIF":5.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956165","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":"Self-reported Clinical Outcomes and Quality of Life in Agammaglobulinemia: the Importance of an Early Diagnosis.","authors":"Maartje Blom, Annelotte J Duintjer, Mahnaz Jamee, Melanie de Gier, Markéta Bloomfield, Adam Klocperk, Pavlina Kralickova, Neslihan E Karaca, Oksana Boyarchuk, Peter Čižnár, Miloš Jeseňák, Svetlana Sharapova, Ekaterina Skopovets, Luis I Gonzalez-Granado, Serena Palmeri, Stefano Volpi, Andrea Martin Nalda, Sonia Rodriguez Tello, Pere Soler-Palacín, Hassan Abolhassani, Federica Pulvirenti, Bianca Cinicola, Uwe Wintergerst, Godelieve J de Bree, J Merlijn van den Berg, Helen L Leavis, Clementien Vermont, Virgil A S H Dalm, Koen van Aerde, Stefanie Henriet, Hetty Jolink, Judith Potjewijd, Arjan Lankester, Chandoshi Rhea Mukherjee, Dagmar Berghuis, Małgorzata Pac, Benjamin M J Shillitoe, Andrew R Gennery, Mirjam van der Burg","doi":"10.1007/s10875-025-01904-z","DOIUrl":"10.1007/s10875-025-01904-z","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with (X-linked) agammaglobulinemia (XLA) suffer from severe, recurrent infections potentially leading to life-threatening complications such as sepsis, meningoencephalitis and chronic lung disease. Early diagnosis and timely treatment can prevent infections and secondary complications, emphasizing a role for early detection of XLA via newborn screening (NBS). Our international multicenter survey study aimed to evaluate self-reported outcomes and parental perspectives in XLA patients to determine whether an early diagnosis is associated with better quality of life (QoL).</p><p><strong>Methods: </strong>QoL-questionnaires included the PedsQL for children and SF-36, CVID_QOL, PADQOL-16 for adults. A new questionnaire was specifically developed for parents about an early diagnosis of XLA.</p><p><strong>Results: </strong>In total, 88 adult and 65 pediatric XLA patients, and 69 parents from 14 countries completed the survey. Patients with an early diagnosis reported less severe, recurrent infections and less hospitalization (p < 0.05). QoL was significantly lower in multiple health domains for pediatric and adult patients with a late diagnosis compared to the general population. Patients with an early diagnosis reported similar QoL outcomes compared to the general population. Parents showed immense support for NBS for XLA stating that an early diagnosis prevents emotional insecurity, health damage, unnecessary diagnostics and allows early access to medical care and informed family planning.</p><p><strong>Conclusion: </strong>Our study has shown supportive evidence to pursue an early diagnosis of XLA from both a self-reported clinical, health related QoL and parental perspective. The main plea from patients and parents is to achieve an early diagnosis for XLA and severe B-lymphocyte deficiencies with NBS.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"125"},"PeriodicalIF":5.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956178","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":"Expanding the Genetic and Clinical Spectrum of Hereditary Angioedema with Normal C1 Inhibitor: Novel Variants and Treatment Insights.","authors":"Haiqing Gao, Ying Zhao, Shengan Chen, Zhen Zhang, Fanping Yang, Zihua Chen, Lanting Wang, Jin Yang, Shan He, Chang Tang, Shenyuan Zheng, Chenggong Guan, Yu Xu, Lin Tang, Aiyuan Zhang, Marcus Maurer, Dylan Lee, Li Ma, Xiaoqun Luo","doi":"10.1007/s10875-025-01912-z","DOIUrl":"https://doi.org/10.1007/s10875-025-01912-z","url":null,"abstract":"<p><p>Hereditary angioedema with normal C1 inhibitor (HAE-nC1-INH) is a rare and genetically heterogeneous disorder with an incomplete molecular understanding. This study aimed to identify novel genetic variants associated with HAE-nC1-INH, characterize their clinical manifestations, and evaluate real-world treatment responses. Whole-exome sequencing of 27 HAE patients, including eight with HAE-nC1-INH, identified four previously unreported MYOF variants and additional pathogenic variants in KNG1 and HS3ST6, expanding the genetic spectrum of the disease. MYOF variants were associated with recurrent edema episodes, often with prolonged duration. The HS3ST6 variant was linked to refractory angioedema with non-resolving lower extremity involvement, highlighting atypical, persistent clinical phenotypes beyond the classical self-limiting presentation of HAE. Lanadelumab effectively reduced attack frequency in most patients; however, the variability in treatment response, particularly in MYOF and HS3ST6 carriers, highlights the need for individualized therapeutic approaches. These findings provide new insights into the genetic and clinical complexity of HAE-nC1-INH and emphasize the importance of genetic testing in refining diagnosis and optimizing treatment strategies, contributing to a more precise understanding of hereditary angioedema.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"124"},"PeriodicalIF":5.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956091","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":"Antisynthetase Syndrome during anti-TNF-alpha Therapy: Report of Two Cases.","authors":"Alexandre-Raphael Wery, Helene Bugaut, Sarah Louis-Leonard, Yves Allenbach, Olivier Benveniste","doi":"10.1007/s10875-025-01925-8","DOIUrl":"https://doi.org/10.1007/s10875-025-01925-8","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"123"},"PeriodicalIF":5.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956106","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 Immunodeficiency Profile of Lymphocytes in the Patient with Moesin Gene Mutation During Different Infection.","authors":"Qian Liu, Ai Zhang, Yuxin Bai, Xinpu Yang, Xinglou Liu, Lu Yang, Yanqin Ying, Xiaoping Luo, Feng Fang, Chaohong Liu","doi":"10.1007/s10875-025-01899-7","DOIUrl":"10.1007/s10875-025-01899-7","url":null,"abstract":"<p><strong>Purpose: </strong>The Ezrin-Radixin-Moesin (ERM) family member moesin (MSN) plays a crucial role in reversibly linking F-actin to the cell membrane. Patients carrying MSN gene mutations consistently exhibit immunodeficiencies. However, due to the scarce number of reported cases worldwide, the mechanism by which MSN mutation leads to immune function defects remains unclear. This study aims to profile the immunological features in MSN mutant patients elaborately.</p><p><strong>Methods: </strong>In this article, we present a case study of a patient with c.511 C > T, p.Arg171Trp (p.R171W) mutation on the MSN gene. We analyzed abnormalities in peripheral immune cell subsets by quantitative analysis, morphological examination, and functional molecule assessment during various infection states. Using total internal reflection fluorescence microscopy (TIRFm), we visualized BCR clusters and F-actin dynamics in B cells, revealing valuable insights into B cell activation and the link between F-actin aggregation and BCR signaling in MSN mutant patients.</p><p><strong>Results: </strong>The results suggest that the MSN c.511 C > T, p.Arg171Trp (p.R171W) mutation affects the proliferation, differentiation, metabolism, and adhesion functions in peripheral immune cells, as well as the maturation process in bone marrow cells. Additionally, we elucidate the impact of MSN mutation on B cell and T cell metabolism and propose a potential diagnostic indicator for patients with MSN gene mutations.</p><p><strong>Conclusion: </strong>Our findings support the diagnosis of primary immunodeficiency and provide detailed insights into changes occurring in immune cells, especially B cells. Overall, our study adds to the diagnosis and pathogenesis of X-linked moesin-associated immunodeficiency (X-MAID).</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"122"},"PeriodicalIF":5.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816755","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}