Journal of Clinical Immunology最新文献

{"title":"Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).","authors":"Qi Wu, Bijun Sun, Jia Hou, Xiaoying Hui, Chenghao Wang, Wenjie Wang, Wenjing Ying, Luyao Liu, Li Zhu, Ying Wang, Qifan Li, Meiping Yu, Weitao Zhou, Yao Chen, Bingbing Wu, Jinqiao Sun, Qinhua Zhou, Feng Qian, Xiaochuan Wang","doi":"10.1007/s10875-024-01812-8","DOIUrl":"10.1007/s10875-024-01812-8","url":null,"abstract":"<p><strong>Objective: </strong>FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis.</p><p><strong>Results: </strong>The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA⁺HLA-DR⁺, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment.</p><p><strong>Conclusions: </strong>We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"23"},"PeriodicalIF":7.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390935","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":"Granulomas in Common Variable Immunodeficiency Display Different Histopathological Features Compared to Other Granulomatous Diseases.","authors":"Astrid C van Stigt, Jan H von der Thüsen, Dana A M Mustafa, Thierry P P van den Bosch, Karishma A Lila, Disha Vadgama, Martin van Hagen, Virgil A S H Dalm, Willem A Dik, Hanna IJspeert","doi":"10.1007/s10875-024-01817-3","DOIUrl":"10.1007/s10875-024-01817-3","url":null,"abstract":"<p><p>Granulomatous disease affects up to 20% of patients with Common Variable Immunodeficiency (CVID). Granulomas are comprised of highly activated immune cells, and emerge in response to antigenic triggers. In CVID granulomas however, the underlying pathophysiology is unclear and the specific trigger remains unknown. Granuloma formation in CVID is often compared to sarcoidosis, although clinical context and prognosis differ, suggesting a different pathogenesis. The aim of this study was to investigate if the cellular organization and proteomics of granulomas in CVID is different from other granulomatous diseases. Therefore, tissue slides from formaldehyde fixed paraffin embedded biopsies obtained from patients with CVID, sarcoidosis, tuberculosis and foreign-material induced pseudo-sarcoidosis were stained with hematoxylin and eosin and assessed for histopathological characteristics. Targeted spatial protein analysis was performed, and immune fluorescent multiplex assays were used to analyze the cellular organization. Histological analysis revealed that CVID granulomas were smaller, less circumscribed, with fewer multinucleated giant cells and minimal fibrosis compared to the other granulomatous diseases. Spatial protein analysis showed that granulomas in all diseases expressed CD68, CD11c, CD44, CD127, and PD-L1. However in CVID, reduced expression of the fibrosis-related protein fibronectin, but enrichment of CD163, CD3 and FAPα inside CVID granulomas was observed. Immunofluorescence analysis conformed a different cellular organization in CVID granulomas with increased influx of neutrophils, macrophages, T and B lymphocytes. In conclusion, granulomas in CVID display a different histological and cellular organization with increased influx of myeloid and lymphoid cells, compared to sarcoidosis, tuberculosis and pseudo-sarcoidosis, indicating a distinct pathogenesis underlying granuloma formation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"22"},"PeriodicalIF":7.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380969","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":"First Brazilian Case Report of Unrelated Patients with Identical ISG15 Mutation.","authors":"Sarah Maria da Silva Napoleao, Ranieri Coelho Salgado, Janaira Fernandes Severo Ferreira, Mayra de Barros Dorna, Thais Costa Lima de Moura, Tábata Takahashi França, Lucila Akune Barreiros, Lillian Nunes Gomes, Antonio Condino-Neto","doi":"10.1007/s10875-024-01811-9","DOIUrl":"10.1007/s10875-024-01811-9","url":null,"abstract":"<p><strong>Background: </strong>ISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy.</p><p><strong>Objective: </strong>To characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant.</p><p><strong>Methods: </strong>We began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families.</p><p><strong>Results: </strong>A mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls.</p><p><strong>Conclusion: </strong>This study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine.</p><p><strong>Clinical implications: </strong>Reporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"21"},"PeriodicalIF":7.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371981","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":"MDA5 gain-of-function associated with a Glu794del mutation.","authors":"Callie Wong, Lukas Gerasimavicius, Yanick J Crow, Carolina Uggenti","doi":"10.1007/s10875-024-01813-7","DOIUrl":"10.1007/s10875-024-01813-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"20"},"PeriodicalIF":7.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361635","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 SAMD9 Variant Causing MIRAGE Syndrome Treated with Subcutaneous Immunoglobulin.","authors":"Christopher T Peek, Manuel Silva-Carmona, Alison A Bertuch, Sarah K Nicholas, Tiphanie P Vogel","doi":"10.1007/s10875-024-01808-4","DOIUrl":"10.1007/s10875-024-01808-4","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"19"},"PeriodicalIF":7.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336435","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":"Health Care Utilisation in a Cohort of Patients with Primary and Secondary Antibody Deficiency in the United Kingdom.","authors":"Benjamin Dimbleby, Will Greenway, Siobhan O Burns, Alex G Richter, Adrian M Shields","doi":"10.1007/s10875-024-01809-3","DOIUrl":"10.1007/s10875-024-01809-3","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the frequency of hospital attendances, emergency care attendances and geographical influences on service interaction in cohorts of patients with primary and secondary antibody deficiency, to inform future service planning and delivery.</p><p><strong>Methods: </strong>The COVID-19 in Antibody Deficiency (COV-AD) study was a United Kingdom study that enrolled 525 participants between April 2021 and September 2022. Data on health care utilisation was extracted from a screening cohort of participants at one participating site (Birmingham, UK). Hospital attendance (i.e. all outpatient and inpatient care episodes, including hospital-based IVIG treatment) and emergency care attendance patterns were analysed. Geographical differences in travel times to hospitals and associated costs were considered for all participants at all recruiting sites.</p><p><strong>Results: </strong>Individuals with antibody deficiency had a median of 7 hospital attendances per year. A diagnosis of secondary antibody deficiency, and antibody deficiency severe enough to require treatment with immunoglobulin replacement were associated with an increased frequency of hospital attendance. 12.7% of the cohort attended the Emergency Department at least once in the preceding twelve months. Individuals with secondary antibody deficiency were at greater risk of requiring emergency care over the preceding one-year and five-year periods. Individuals receiving subcutaneous immunoglobulin lived further from their local immunology centre and were more likely to engage with the COV-AD research study remotely, via dried blood spots sampling.</p><p><strong>Conclusion: </strong>This study highlights the utilisation of emergency and secondary care usage amongst patient with immunodeficiency and may inform service adaptation and development to better accommodate patient needs and circumstances.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"18"},"PeriodicalIF":7.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347685","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":"Characteristics of Endemic Mycoses Talaromyces marneffei Infection Associated with Inborn Errors of Immunity.","authors":"Shubin Xing, Zhenzhen Zhang, Cong Liu, Wenjing Zhang, Zhiyong Zhang, Xuemei Tang, Yongwen Chen, Wuyang He, Xiaodong Zhao, Yunfei An","doi":"10.1007/s10875-024-01798-3","DOIUrl":"10.1007/s10875-024-01798-3","url":null,"abstract":"<p><strong>Background: </strong>Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children.</p><p><strong>Objective: </strong>We conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies.</p><p><strong>Methods: </strong>A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected.</p><p><strong>Results: </strong>Fifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals.</p><p><strong>Conclusions: </strong>The XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"17"},"PeriodicalIF":7.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347684","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":"Investigation of Transcription Factor and Cytokine Gene Expression Levels in Helper T Cell Subsets Among Turkish Patients Diagnosed with ICF2 (Novel ZBTB24 gene Variant) and ICF3 (CDCA7 Variant) Syndrome.","authors":"Tugce Duran, Mehmet Ali Karaselek, Serkan Kuccukturk, Yahya Gul, Ali Sahin, Sukru Nail Guner, Sevgi Keles, Ismail Reisli","doi":"10.1007/s10875-024-01807-5","DOIUrl":"10.1007/s10875-024-01807-5","url":null,"abstract":"<p><p>Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF), is a rare disease with autosomal recessive inheritance. ICF syndrome. It has been reported that ICF syndrome is caused by mutations in the DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) genes. As a result of literature research, there are no studies on transcription factor and cytokine expressions of helper T cell subsets in ICF syndrome. In the study; Th1 (TBET, STAT1, STAT4), Th2 (GATA3, STAT6), Th17 (RORgt, STAT3), Treg (FoxP3, STAT5) transcription factors and the major cytokines of these cells (Th1; IFNG, Th2; IL4, Th17; IL17A-21-22, Treg; IL10, TGFβ) expressions were aimed to be evaluated by qRT-PCR. Patients (ICF3: three patients; ICF2: two patients), six heterozygous individual and five healthy controls were included in the study. All patients had hypogammaglobulinemia. Except for the CD19 cells of P2 from patients diagnosed with ICF3, the CD3, CD4, CD8, and CD19 cells in the other ICF3 patients were normal. However, the rates of these cells were low in patients with ICF2 syndrome. Factors belonging to patients' Th1, Th17 and Treg cells were significantly lower than the control. Additionally, novel mutation was detected in ZBTB24 gene (c.1121-2 A > T). Our study is the first molecular study on Th cell subsets in patients with ICF syndrome and a new mutation that causes ICF2 syndrome has been identified.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"16"},"PeriodicalIF":7.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347686","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":"Biallelic PI4KA Mutations Disrupt B-Cell Metabolism and Cause B-Cell Lymphopenia and Hypogammaglobulinemia.","authors":"Francesco Saettini, Fabiola Guerra, Mario Mauri, Claire G Salter, Margaret P Adam, David Adams, Emma L Baple, Estibaliz Barredo, Sanil Bhatia, Arndt Borkhardt, Alfredo Brusco, Cristina Bugarin, Clizia Chinello, Andrew H Crosby, Precilla D'Souza, Vanna Denti, Grazia Fazio, Silvia Giuliani, Hye Sun Kuehn, Hassan Amel, Asha Elmi, Bernice Lo, Federica Malighetti, Giorgia Mandrile, Andrea Martín-Nalda, Heather C Mefford, Daniele Moratto, Fatemeh Emam Mousavi, Zoe Nelson, Luis González Gutiérrez-Solana, Ellen Macnamara, Vincent Michaud, Melanie O'Leary, Lisa Pagani, Lisa Pavinato, Patricia VVelez Santamaria, Laura Planas-Serra, Manuel Quadri, Miquel Raspall-Chaure, Stefano Rebellato, Sergio D Rosenzweig, Agathe Roubertie, Dirk Holzinger, Christin Deal, Catherine Walsh Vockley, Angela Maria Savino, Jennifer L Stoddard, Holm H Uhlig, Aurora Pujol, Fulvio Magni, Giuseppe Paglia, Gianni Cazzaniga, Rocco Piazza, Matteo Barberis, Andrea Biondi","doi":"10.1007/s10875-024-01793-8","DOIUrl":"10.1007/s10875-024-01793-8","url":null,"abstract":"<p><strong>Purpose: </strong>PI4KA-related disorder is a highly clinically variable condition characterized by neurological (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus) and gastrointestinal (inflammatory bowel disease and multiple intestinal atresia) manifestations. Although features consistent with immunodeficiency (autoimmunity/autoinflammation and recurrent infections) have been reported in a subset of patients, the burden of B-cell deficiency and hypogammaglobulinemia has not been extensively investigated. We sought to describe the clinical presentation and manifestations of patients with PI4KA-related disorder and to investigate the metabolic consequences of biallelic PI4KA variants in B cells.</p><p><strong>Methods: </strong>Clinical data from patients with PI4KA variants were obtained. Multi-omics analyses combining transcriptome, proteome, lipidome and metabolome analyses in conjunction with functional assays were performed in EBV-transformed B cells.</p><p><strong>Results: </strong>Clinical and laboratory data of 13 patients were collected. Recurrent infections (7/13), autoimmune/autoinflammatory manifestations (5/13), B-cell deficiency (8/13) and hypogammaglobulinemia (8/13) were frequently observed. Patients' B cells frequently showed increased transitional and decreased switched memory B-cell subsets. Pathway analyses based on differentially expressed transcripts and proteins confirmed the central role of PI4KA in B cell differentiation with altered B-cell receptor (BCR) complex and signalling. By altering lipids production and tricarboxylic acid cycle regulation, and causing increased endoplasmic reticulum stress, biallelic PI4KA mutations disrupt B cell metabolism inducing mitochondrial dysfunction. As a result, B cells show hyperactive PI3K/mTOR pathway, increased autophagy and deranged cytoskeleton organization.</p><p><strong>Conclusion: </strong>By altering lipid metabolism and TCA cycle, impairing mitochondrial activity, hyperactivating mTOR pathway and increasing autophagy, PI4KA-related disorder causes a syndromic inborn error of immunity presenting with B-cell deficiency and hypogammaglobulinemia.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"15"},"PeriodicalIF":7.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288329","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":"Concomitant Ultrarare Mutations in TLR3 and CTPS2 in a Patient with Severe and Recurrent Respiratory Infections in Early Life.","authors":"Salim Bougarn, Andrea Guennoun, Taushif Khan, Rafah Mackeh, Mehdi Adeli, Nico Marr","doi":"10.1007/s10875-024-01804-8","DOIUrl":"10.1007/s10875-024-01804-8","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"14"},"PeriodicalIF":7.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288330","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}