Journal of Clinical Immunology最新文献

{"title":"De Novo Missense Variant c.170 C > A of ELANE in a Chinese Infant with Congenital Neutropenia: Case Report and Literature Review.","authors":"Xinying Chen, Xiaoxin Zhao, Bo Pan, Lianyu Wang, Wensi Xie, Wenwen Jiang, Jinghua Yang, Weixia Wu, Yanxin Li","doi":"10.1007/s10875-025-01905-y","DOIUrl":"10.1007/s10875-025-01905-y","url":null,"abstract":"<p><p>Congenital neutropenia (CN) is a rare hereditary blood disorder characterized by a significant reduction in neutrophils, making patients prone to recurrent and severe infections and even a risk of developing myelodysplastic syndrome or acute leukemia, often caused by the ELANE variants, and the complex relationship between ELANE variants and clinical phenotypes, as well as the natural course of the disease, remains unclear. We describe a case of CN in a Chinese infant caused by the De Novo missense variant c.170 C > A in the ELANE gene, presented with persistent neutropenia since the neonatal period, accompanied by recurrent infections. He did not receive G-CSF treatment due to the declination of his parents, but antibiotics were administered during infections or with high hsCRP levels. During the early neonatal stage, the patient consistently exhibited severe neutropenia (ANC < 0.5 × 10^9/L). Periodic fluctuations in neutrophil counts observed twice a week during particular months suggest a cyclical pattern. Until now, he still experiences varying degrees of neutropenia persistently, with ANC occasionally exceeding 1.0 × 10^9/L during infections. Multiple prediction scoring tools and models support the pathogenicity of this missense variant. This case highlights a rare pathogenic variant of ELANE, which, to our knowledge, is the first case of the variant c.170 C > A (p.Ala57Asp) of the intermediate phenotype of CN in mainland China and a rare variant globally, indicating phenotypic variability in ELANE-related neutropenia due to an Ala57 mutation. The clinical management of CN caused by ELANE variants poses a challenge for clinicians and deserves attention. Timely diagnosis, treatment, and extended follow-up are of paramount value.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"113"},"PeriodicalIF":7.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618135","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":"Evaluation of a Multiplex Electrochemiluminescence Assay for Detection of Anti-Pneumococcal Antibodies in the Diagnosis of Selective Polysaccharide Antibody Deficiency.","authors":"Nicolas Perrard, Aurore Collet, Sarah Stabler, Sandrine Poizot, Myriam Labalette, Gatien Durand, Frédéric Batteux, Floriane Mirgot, Benjamin Lopez, Sylvain Dubucquoi, Lucie Chevrier, Guillaume Lefèvre","doi":"10.1007/s10875-025-01911-0","DOIUrl":"10.1007/s10875-025-01911-0","url":null,"abstract":"<p><p>Streptococcus pneumoniae can be responsible for severe infections, especially in patients with primary antibody deficiencies like selective anti-polysaccharide antibodies deficiency (SPAD). The reference method recommaned by the World Health Organization for assessment of anti-pneumococcal capsular polysaccharides (PCPs) IgG antibodies is a standardized serotype-specific ELISA (WHO-SSA), but this manual method is time-consuming and limit the number of evaluated PCPs. We aim to evaluate the performance values of a multiplex assay based on electrochemiluminescence (ECL-plex). A panel of 164 sera from 82 patients sampled before and 4-8 weeks after immunization by the 23-valent pneumococcal polysaccharide vaccine (PPV23) were assessed by the reference WHO-SSA (7 to 13 serotypes) and by an 18-plex ECL assay (18 serotypes). All patients had normal serum Ig/subclasses levels and were classified as good (n = 43) or poor responders (n = 39, i.e. SPAD patients) according to the American Academy of Asthma, Allergy and Immunology's (AAAAI) current guidelines. We observed excellent correlations between the two methods for anti-PCPs titers against 7 serotypes (r = 0.88 [95% CI: 0.87-0.90], n = 124 sera) and 13 serotypes (r = 0.87 [0.87-0.89], n = 40 sera). Using the AAAAI's guidelines for interpretation, the test performance of the 18-plex ECL assay for SPAD diagnosis showed a sensitivity of 95% and specificity of 84%, positive and negative predictive values of 84% and 95%, respectively. The percentage of agreement was 89% between the SSA and the 18-plex ECL assay. The 18-plex ECL assay is a reliable, rapid, and simple method for evaluating anti-PCPs response and screening for SPAD diagnosis.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"112"},"PeriodicalIF":7.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600616","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":"Somatic Mosaic NLRC4 Variants in Autoinflammatory Diseases: Functional Characterization and Correlation of Mosaicism Levels with Disease Age of Onset and Severity.","authors":"Farah Diab, Camille Louvrier, Marc Fabre, Christine Lin, Mira Rabbaa, Eman Assrawi, Aphrodite Daskalopoulou, Rahma Mani, Florence Dastot Le Moal, William Piterboth, Marie Legendre, Serge Amselem, Sonia Athina Karabina, Irina Giurgea","doi":"10.1007/s10875-025-01907-w","DOIUrl":"10.1007/s10875-025-01907-w","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"111"},"PeriodicalIF":7.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584072","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":"Successful Treatment of Skin Dyskeratosis Due To NLRP1 Mutation Using Baricitinib.","authors":"Gokce Vatansever, Zuhal Karali, Yasin Karali, Hasibe Artac, Sara Sebnem Kilic","doi":"10.1007/s10875-025-01909-8","DOIUrl":"10.1007/s10875-025-01909-8","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"110"},"PeriodicalIF":7.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567439","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":"Clinicopathological and Immunogenetic Characterization in 8 Patients with Familial Hemophagocytic Lymphohistiocytosis Type 2: A Study from North India with Literature Review.","authors":"Saniya Sharma, Suprit Basu, Taru Goyal, Madhubala Sharma, Prabal Barman, Gurjit Kaur, Jitendra K Shandilya, Pandiarajan Vignesh, Rakesh Kumar Pilania, Ankur Kumar Jindal, Manpreet Dhaliwal, Prateek Bhatia, Sreejesh Sreedharanunni, Pulkit Rastogi, Nabhajit Mallik, Prashant Sharma, Anupriya Kaur, Deepti Suri, Amit Rawat, Surjit Singh","doi":"10.1007/s10875-025-01895-x","DOIUrl":"10.1007/s10875-025-01895-x","url":null,"abstract":"<p><p>Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) is the commonest cause of familial hemophagocytic lymphohistiocytosis (FHLH). In this retrospective study, we analyzed 8 patients with a genetic diagnosis of FHL2 and then examined their clinicopathological and perforin flow cytometry results (< 10% expression). The atypical clinical features in our cohort included tuberculosis, lymphoreticular malignancy, and necrotizing enterocolitis in 3 patients. A disease-causing variant was identified in the PRF1 gene in all eight patients, comprising missense (n = 6), null (n = 1), and in-frame deletion (n = 1). Five patients had homozygous exon 3 disease-causing variants, two had homozygous exon 2 disease-causing variants, and one had compound heterozygous disease-causing variants in exon 2 and exon 3. After an extensive literature search, the mutations present in our North Indian cohort, including c.1284G > A, c.895C > T, c.853_855del, c.203G > A, and c.757G > A, are reported for the first time from India. Clinical and immunological phenotypes of c.1284G > A and c.203G > A variants have not been published in the literature. Hemophagocytosis was evident in bone marrow in 6 cases. Hyperferritinemia was absent in 3 cases, including c.148G > A, c. 895C > T, and c.1349C > T homozygous variants. Neurological involvement, lymphoreticular malignancy, and necrotizing enterocolitis were seen in 2, 1, and 1 cases, respectively. Infections were present in 4 cases. Five children succumbed to HLH, and three are alive and planned for a hematopoietic stem cell transplant. FHL2 should be suspected in children with HLH irrespective of the age of onset, atypical clinical phenotype, family history, ferritin and fibrinogen levels, and infections. Flow cytometry-based perforin assay helps in rapid diagnosis of FHL2.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"108"},"PeriodicalIF":7.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325921","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":"BK Virus-Specific T Cell Response Associated with HLA Genotypes, RhD Status, and CMV or EBV Serostatus in Healthy Donors for Optimized Cell Therapy.","authors":"Rut Mora-Buch, Maria Tomás-Marín, Helena Pasamar, Emma Enrich, Cleofé Peña-Gómez, Francesc Rudilla","doi":"10.1007/s10875-025-01901-2","DOIUrl":"10.1007/s10875-025-01901-2","url":null,"abstract":"<p><strong>Purpose: </strong>The increasing application of virus-specific T cell therapy for treating BK virus infections in immunocompromised patients highlights the necessity for rapid identification of compatible cell donors with optimal BK-specific T cell response. This study aims to characterize the BK virus-specific T cell response in relation to demographic factors, blood group, serological status, and HLA genotypes using samples from a cell donor registry.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells from cell donors were stimulated with peptide pools derived from VP1 and LTA proteins, and the IFN-γ production was analyzed using ELISpot and validated by flow cytometry.</p><p><strong>Results: </strong>Our findings provide an overview of the T cell response to BK virus proteins in healthy donors, revealing associations with demographic characteristics, RhD status, CMV or EBV serological status, and HLA alleles. Remarkably, RhD-negative, CMV-seronegative, and EBV-seronegative donors showed a major T cell response against BK virus proteins. Notably, certain HLA alleles were associated with either enhanced or diminished T cell response. Furthermore, our results suggest that HLA-B leader dimorphism, specifically the presence of threonine at position 2, influences the VP1-specific immune response, resulting in enhanced T cell activation.</p><p><strong>Conclusion: </strong>This study, beyond advancing our understanding of the relationship between donor characteristics and BK virus-specific T cell response, has significant implications for improving the selection of optimal cell donors for patient-specific adoptive therapy.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"109"},"PeriodicalIF":7.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333186","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":"NET Proteomic Profiling Reveals New Pathways Potentially Implicated in Dendritic Cell-Mediated Inflammation in DADA2 Patients.","authors":"Sara Signa, Martina Bartolucci, Martina Bonacini, Arinna Bertoni, Genny Del Zotto, Anna Corcione, Andrea Petretto, Silvia Della Bella, Roberta Bertelli, Dario Di Silvestre, Andrea Lomagno, Pierluigi Mauri, Roberta Caorsi, Maurizio Bruschi, Simone Balin, Paola Bocca, Stefano Volpi, Maria Grazia Catanoso, Alessia Cafaro, Gino Tripodi, Lorenzo Pellottieri, Domenico Mavilio, Antonella Insalaco, Stefania Croci, Carlo Salvarani, Marco Gattorno, Francesca Schena","doi":"10.1007/s10875-025-01888-w","DOIUrl":"10.1007/s10875-025-01888-w","url":null,"abstract":"<p><strong>Purpose: </strong>Adenosine deaminase 2 Deficiency (DADA2) is an autoinflammatory disease characterized by systemic vasculopathy, strokes and mild immunodeficiency. Recently NETosis has been implicated in the pathogenesis of Deficiency of Adenosine Deaminase 2. To deep investigate the possible effects of NETs on the immune system we characterized proteomic profile of NETs from DADA2 as compared to HD and Polyarteritis Nodosa (PAN) patients. To determine if NETs contain possibly immunogenic antigens we study functional aspects on Dendritic Cells after in vitro stimulation with NETs.</p><p><strong>Methods: </strong>Twenty-three DADA2 patients were enrolled. We analyzed NETosis by Imaging Flow Citometry. We evaluated NETs remnants and DNAse in the plasma samples by ELISA assay whereas DNAse activity by DNA digestion. We used quantitative proteomics approach and network analysis to identify NET proteins and pathways in 6 DADA2, 7 PAN and 7 HD. We analyzed circulating and monocyte-derived dendritic cells by flow cytometry.</p><p><strong>Results: </strong>Neutrophils from DADA2 patients show a significant increased suicidal NETosis. DNAse enzymes were not normal in the level or activity. By proteomic analysis we identified 1356 proteins among which a hundred of proteins were significantly up or down-modulated in DADA2 NETs as compared to normal and disease control NETs in resting condition and after stimulation with PMA, Adenosine and TNFα. DADA2 NETs are significantly more efficient than normal NETs in stimulating patients' monocyte-derived dendritic cells.</p><p><strong>Conclusion: </strong>We identified different pathways significantly modulated in DADA2 NETs versus PAN/HD NETs. This peculiar protein profile could contribute in activating inflammatory pathways in Dendritic cells in DADA2.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"106"},"PeriodicalIF":7.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302208","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":"Correction to: Newborn Screening Followed By Early Treatment is Essential to Improve Survival in SCID.","authors":"Gabriela Assunção Goebel, Luciana Araújo Oliveira Cunha, Fernanda Gontijo Minafra, Jorge Andrade Pinto","doi":"10.1007/s10875-025-01902-1","DOIUrl":"10.1007/s10875-025-01902-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"107"},"PeriodicalIF":7.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302207","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":"Safety and Efficacy of Intravenous Immune Globulin 10% (BIVIGAM^®) in Children with Primary Immune Deficiency.","authors":"Isaac Melamed, Jolan E Walter, Oral Alpan, Jennifer W Leiding","doi":"10.1007/s10875-025-01891-1","DOIUrl":"10.1007/s10875-025-01891-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"105"},"PeriodicalIF":7.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266392","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":"Unresolved Issues in Familial Mediterranean Fever: Is p.R202Q MEFV Variant Potentially Pathogenetic in Unleashing Inflammation?","authors":"Chiara Baggio, Francesca Oliviero, Paola Galozzi, Irina Guidea, Andrea Doria, Roberta Ramonda, Sara Bindoli, Paolo Sfriso","doi":"10.1007/s10875-025-01898-8","DOIUrl":"10.1007/s10875-025-01898-8","url":null,"abstract":"<p><p>Familial Mediterranean Fever (FMF) is caused by mutations in the MEFV gene, which encodes for pyrin. Although genetic testing is commonly employed for FMF diagnosis, the interpretation of genetic results is often challenging. Therefore, we aimed to functionally characterise the p.R202Q MEFV alteration. Furthermore, we hypothesized that inflammation may affect genomic stability and neutrophilic (N) subsets. A cohort comprising patients with FMF (n = 4), p.R202Q variant (n = 18) and FMF-like (n = 8) were selected from the Outpatient Clinic for Autoinflammatory diseases of Padova University Hospital. Primary monocytes were incubated for 3 h in the presence of LPS or LPS + PKN1/2 inhibitor (UCN-01). Colchicine pretreatment was applied to assess its anti-inflammatory effect. Pro-inflammatory cytokines were measured by ELISA and leukocytes were examined using May-Grünwald-Giemsa staining on blood smears. We did not find significant differences in IL-1 and IL-18 levels in monocytes treated with LPS + UCN-01 between p.R202Q patients and healthy donors (HDs). The levels of IL-1β released from LPS-stimulated patients were higher in p.R202Q patients than in HDs. We found that immature and hypersegmented neutrophils were higher in p.R202Q patients than in HD. Nuclear abnormalities were higher in FMF and p.R202Q patients than in HD. Finally, we found a higher cell rate in leukocytes from p.R202Q patients than in HDs. The p.R202Q variant did not appear to affect pyrin function, albeit these patients presented cytological alterations similar to those observed in FMF patients. These changes may contribute to FMF pathophysiology by influencing inflammation progression.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"104"},"PeriodicalIF":7.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258179","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}