Journal of Clinical Immunology最新文献

{"title":"A Novel Phosphoglucomutase-3 Gene Variant Causing Milder Phenotype in Two Families.","authors":"Betul Gemici Karaaslan, Mehdi Benamar, Selami Ulas, Sezin Aydemir, Gozde Yesil, Alper Gezdirici, Aysun Ayaz Sari, Serdar Nepesov, Haluk Cokugras, Yildiz Camcioglu, Akif Ayaz, Cigdem Aydogmus, Louis-Marie Charbonnier, Talal Chatila, Ayca Kiykim","doi":"10.1007/s10875-026-02012-2","DOIUrl":"10.1007/s10875-026-02012-2","url":null,"abstract":"<p><p>BACKGROUND: Phosphoglucomutase 3 deficiency (PGM3 deficiency) is a rare congenital disorder of glycosylation classically associated with severe immunodeficiency, skeletal abnormalities, and neurodevelopmental impairment. However, emerging evidence suggests that PGM3 deficiency may also present with attenuated or milder clinical phenotypes. In this study, we describe patients with a novel PGM3 variant exhibiting a less severe immunological and clinical presentation, thereby expanding the known phenotypic spectrum of PGM3 deficiency. METHODS: Demographic-data and Wechsler Intelligence Scale for Children profiles were evaluated alongside laboratory data, including complete blood cell counts, lymphocyte subsets, serum immunoglobulin levels, vaccine antibody titers, and lymphocyte cytokine profiles. Whole exome sequencing was conducted, and phospho-flow assays were utilized for the analysis of p-STATs. RESULTS: Five patients with a mild form of PGM3 deficiency were described, exhibiting a Hyper-IgE Syndrome phenotype without severe skeletal dysplasia or dysmorphism, with the exception of one patient displaying very mild skeletal dysplasia and three patients exhibiting mild to moderate intellectual disability. All patients demonstrated an increase in Natural Killer T cells and a decrease in B cells, alongside an increase in activated CD4 + T cells (CD45RO+), a decrease in naïve CD4 + and CD8 + T cells (CD45RA+ CCR7+), and an increase in TEMRA CD8 + T cells (CD45RA+CCR7–). Functional analysis of all patients revealed impaired PGM3 function, as evidenced by decreased surface expression of gp130 and p-STAT3. CONCLUSION: Defective glycosylation in PGM3 deficiency leads to reduced gp130 expression and attenuated gp130-dependent STAT3 phosphorylation. The resulting cellular features partially overlap with those observed in STAT3 loss-of-function and gp130 deficiency, supporting a shared signaling mechanism while remaining clinically distinct. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574258","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":"Optical Genome Mapping for the Identification of Complex Structural Variants in Hereditary Angioedema.","authors":"Laura Batlle-Masó, Kornelia Neveling, Johana Gil-Serrano, Eveline Kamping, Amber den Ouden, Raoul Timmermans, Aina Bruch-Tàrrega, Aina Aguiló-Cucurull, Janire Perurena-Prieto, Paula Fernández-Álvarez, Marloes Steehouwer, Alexander Hoischen, Mar Guilarte, Roger Colobran","doi":"10.1007/s10875-026-02015-z","DOIUrl":"10.1007/s10875-026-02015-z","url":null,"abstract":"<p><p>PURPOSE: Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is caused by heterozygous pathogenic variants in the SERPING1 gene. Structural variants (SVs) account for 10–15% of cases, and while many can be identified using conventional diagnostic approaches such as multiplex ligation-dependent probe amplification (MLPA), some remain difficult to detect. This study aims to assess the utility of optical genome mapping (OGM) for the detection of both typically described and atypical structural variants in HAE-C1INH. METHODS: MLPA, OGM, long-read whole-genome sequencing (LR-WGS), Sanger sequencing and cDNA analysis. RESULTS: First, we assessed whether OGM could detect common SVs in HAE-C1INH affecting the SERPING1 coding region. We tested a family previously diagnosed by MLPA with a large heterozygous deletion encompassing exons 1–2 of SERPING1. OGM successfully identified this deletion in both affected members. Next, we analyzed a three-generation HAE-C1INH family with no genetic findings after Sanger sequencing and MLPA. OGM revealed a 3.8 kb insertion in SERPING1, which was further characterized using LR-WGS as a SINE-VNTR-Alu (SVA) mobile element inserted in intron 7, demonstrating the complementary role of LR-WGS in precisely defining the nature and location of SVs detected by OGM. Finally, we demonstrated that the allele carrying the SVA insertion was absent in cDNA resulting in SERPING1 functional haploinsufficiency in this family. CONCLUSION: OGM is a reliable and robust technique for detecting SVs affecting both coding and non-coding regions in HAE-C1INH. Using OGM, we report the first case of HAE-C1INH caused by the insertion of an SVA mobile element. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529367","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":"Allogeneic Hematopoietic Cell Transplantation for Congenital Athymia: A Nationwide Retrospective Study in Japan.","authors":"Tsubasa Nishinosono, Hideki Muramatsu, Manabu Wakamatsu, Motoshi Sonoda, Katsuhide Eguchi, Koji Kawaguchi, Takeshi Yamamoto, Takahiro Kudo, Michiko Kajiwara, Masataka Ishimura, Yoshiyuki Takahashi","doi":"10.1007/s10875-026-02008-y","DOIUrl":"10.1007/s10875-026-02008-y","url":null,"abstract":"<p><strong>Purpose: </strong>Congenital athymia is a life-threatening condition characterized by thymic absence and profound T-cell immunodeficiency. Thymus implantation is the definitive treatment, but its availability is limited. This study aimed to evaluate the outcomes of hematopoietic cell transplantation (HCT) as an alternative therapy.</p><p><strong>Methods: </strong>A nationwide, multicenter, retrospective study analyzed nine patients who underwent allogeneic HCT between 2000 and 2024 in Japan. Overall survival (OS) was estimated using the Kaplan-Meier method, and the cumulative incidence of immunodeficiency-related mortality was assessed using Gray's test.</p><p><strong>Results: </strong>Among the nine patients, eight (89%) received umbilical cord blood, and one (11%) received related peripheral blood. Seven patients (78%) underwent transplantation without conditioning. Engraftment with T-cell recovery was achieved in six patients (67%), with a median CD4⁺ T-cell count of 0.352 × 10⁹/L (range, 0.216-1.578 × 10⁹/L) at the last follow-up. Acute graft-versus-host disease (GVHD) occurred in five patients (56%), all with Grade I-II skin involvement. No chronic GVHD was observed. The one-year OS rate was 66.7% (95% confidence interval: 28.2%-87.8%). Overall, six patients (67%) died: three early deaths within the first month from infections, and three late deaths beyond 1 year from congenital comorbidities. HCT before six months of age was associated with significantly lower immunodeficiency-related mortality (p = 0.02).</p><p><strong>Conclusion: </strong>HCT can allow immune reconstitution in congenital athymia, although long-term survival is affected by comorbidities. Early diagnosis and timely intervention are crucial in managing this condition. HCT can be a restricted alternative therapy for patients ineligible for thymus implantation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574180","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":"Mechanistic Insights Into Immune Cell Dysregulation Mediated by Novel Heterozygous Variants in CARD11 and MALT1.","authors":"Rui Li, Xiaochen Sun, Wei Bao, Haolan Yu, YuQing Dan, Chunmei Wu, Yan Ma, Hanlin Yin, Wanyi Lin, Liangjing Lu, Qiong Fu, Chenghua Yang","doi":"10.1007/s10875-026-02011-3","DOIUrl":"10.1007/s10875-026-02011-3","url":null,"abstract":"<p><p>Dysregulation of the CARD11-BCL10-MALT1 (CBM) complex is associated with a group of inborn errors of immunity termed “CBM-opathies,” which encompass a spectrum of clinical manifestations including combined immunodeficiency, autoimmune inflammation, atopic disorders, and lymphoproliferation. In this study, we identified novel compound heterozygous variants in the CBM complex in a patient with a family history of immune dysfunction. The patient inherited the variants CARD11 p.K215N and MALT1 p.K543R/p.M732T from asymptomatic carrier parents. Phenotypically, the patient exhibited a developmental arrest of B lymphocytes at the transitional/naïve B cell stage, accompanied by activation of virus-response pathways. Impaired development of T follicular helper cells was linked to defective germinal center formation and agammaglobulinemia. Furthermore, the patient showed expansion of T peripheral helper cells and a deficiency in regulatory T cells, both associated with autoimmunity and colitis. In vitro studies confirmed an imbalance in Tph/Tfh cell differentiation. Single-cell RNA sequencing further revealed a deficiency in B cell development and an enriched population of pro-inflammatory CD3dimCD4−CD8−CD247+ T cells, functionally enriched in the MAPK signaling pathway. Mechanistically, the MALT1 K543R and M732T variants attenuated MALT1’s enzymatic activity and compromised its protein stability, while the CARD11K215N variant disrupted CARD11-mediated promotion of BCL10 filament formation. We demonstrated that these three variants act synergistically to impair NF-κB activation. Specifically, CARD11K215N cooperates with the co-pathogenic MALT1M732T and the modifier variant MALT1K543R to destabilize the functional integrity of the CBM complex, thereby driving the patient’s phenotype. In summary, our study provides new insights into the pathogenesis of autoimmune inflammatory disorders within the spectrum of CBM-opathies and reveals a potential role for the CBM complex in regulating the balance between T peripheral helper and T follicular helper cells.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Pathogenic Variant in TRAC Gene Associated with SCID Phenotype: Expanding the Genetic and Clinical Spectrum.","authors":"Mehmet Ali Karaselek, Mehmet Yavuz Ozbey, Vedat Uygun, Serkan Kuccukturk, Necdet Karabey, Ugur Tokdemir, Gokhan Ozel, Zeynep Dilruba Demircioglu, Serhat Yildirim, Ali Sahin, Tugce Duran, Abdullah Akkus, Selman Yildirim, Sukru Guner, İsmail Reisli, Sevgi Keles","doi":"10.1007/s10875-026-02003-3","DOIUrl":"10.1007/s10875-026-02003-3","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic variants in the T-cell receptor alpha constant (TRAC) gene have been primarily associated with combined immunodeficiency (CID). To date, only five patients from three unrelated families harboring the same TRAC variant with a CID phenotype, and three patients carrying a distinct variant with severe combined immunodeficiency (SCID), have been described. We report a previously unreported homozygous TRAC variant causing a premature stop codon in three siblings with classical SCID phenotype.</p><p><strong>Methods: </strong>Comprehensive immunological and molecular analyses were performed, including lymphocyte immunophenotyping, proliferation assays, qPCR for T helper (Th) subset-related gene expression, and cytokine secretion profiling. In silico analyses included conservation assessment, structural modeling using ChimeraX, and protein stability prediction via PremPS to evaluate the variant's structural and functional consequences.</p><p><strong>Results: </strong>All three siblings exhibited recurrent infections, refractory diarrhea, and elevated liver enzymes, accompanied by profound T-cell lymphopenia with preserved B-cell numbers. Whole-exome sequencing revealed a homozygous TRAC variant in the affected siblings and heterozygous carriage in their parents. The variant alters a highly conserved residue, disrupting hydrogen bonding and likely destabilizing the protein structure. Functional assays demonstrated a marked reduction in recent thymic emigrants (RTEs) cell ratio absence of TCRαβ⁺ T cells, skewed Th polarization, and elevated proinflammatory cytokine levelsfindings consistent with a SCID phenotype.</p><p><strong>Conclusion: </strong>These findings expand the clinical and molecular spectrum of TRAC-related immunodeficiency and support its inclusion among genes primarily associated with SCID. The results further emphasize that specific mutation sites within immune-related genes critically influence disease severity and phenotype variability.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512539","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":"Enhancing Clinical Workflow Efficiency in Flow Cytometry Reporting with LLMs.","authors":"Thomas E Tavolara, Jake Meyer, Christopher Garcia, Attila Kumanovics, Patrick Vanderboom","doi":"10.1007/s10875-026-02006-0","DOIUrl":"10.1007/s10875-026-02006-0","url":null,"abstract":"<p><p>BACKGROUND: Accurate interpretation of clinical test results is essential for diagnosing and managing complex immunological disorders. We explored the potential of large language models (LLMs) to automate interpretative reports for immunodeficiency and immune competence assessment via quantitative lymphocyte profiling and B-cell subset phenotyping (QLP/BSP). METHODS: An LLM was fine-tuned using parameter-efficient techniques on a dataset consisting of immunophenotyping test results and corresponding interpretive reports. Model performance was compared against a retrieval-based method and expert pathologist reports. A novel automated evaluation framework assessed both the accuracy of cell population comments and the clinical relevance of generated interpretations. A custom application was built to simulate clinical workflows and measure the impact on pathologist efficiency and accuracy. RESULTS: Fine-tuned LLMs achieved accuracy comparable to expert pathologists in identifying and commenting on abnormal cell type counts and frequencies, in comparison the retrieval-based method exhibited substantial error rates. There was no significant difference between the rate at which abnormalities for cell subtypes were commented on between the LLMs and pathologists. More importantly, LLMs significantly reduced the time required for a single pathologist to finalize reports with a mean reduction in time of 29%. CONCLUSION: Our results suggest that LLMs hold promise for enhancing efficiency and consistency in the clinical laboratory setting. By automating aspects of interpretive reporting, LLMs can potentially reduce pathologist workload and improve the turnaround time for critical diagnostic information, while requiring expert pathologist oversight. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512544","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":"GATA2 Deficiency Syndrome: A Case Series and Literature Review.","authors":"Zhangtong Dong, Jian Lai, Jianguo Li, Yumo Du, Lin Lin, Rui Chen, Mogang Gong, Yongxun Zhuansun","doi":"10.1007/s10875-026-02013-1","DOIUrl":"10.1007/s10875-026-02013-1","url":null,"abstract":"<p><p>GATA2 functions as a critical zinc finger transcription factor and plays indispensable roles in hematopoiesis, immune regulation, and lymphatic vascular development. GATA2 deficiency underlies a diverse phenotypic spectrum, encompassing primary lymphedema, myelodysplasia, acute myeloid leukemia, immune dysfunction, and sensorineural deafness. This report describes three sporadic cases of GATA2 deficiency syndrome and summarizes their clinical features in the context of previously published literature. All three patients carried germline pathogenic GATA2 variants: NM_001145661.1 c.818dupG (p. Pro274Thrfs; case 1) and NM_032638.5 c.1084 C > T (p. Arg362*; cases 2 and 3). The clinical presentations included recurrent pulmonary infections, leukopenia, and thrombocytopenia (case 1) and congenital neurogenic deafness (cases 2 and 3).</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504132","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":"Excluded GM-specific IgG Subclass Genes in Health and Disease - Inborn Errors of Immunity.","authors":"Vivi-Anne Oxelius","doi":"10.1007/s10875-026-02001-5","DOIUrl":"10.1007/s10875-026-02001-5","url":null,"abstract":"<p><p>PURPOSE: IgG subclass genes from chromosome 14q32.3 are assessed serologically by GM allotypes, genetic markers of the Fc part of the immunoglobulin constant heavy G chains, (IGHG(Fcγ)(GM) genes. Alternative GM allotypes of IgG3, IgG1 and IgG2, respectively, define 6 unique, precise GM-specific IgG subclass genes, inherited the Mendelian way with allelic exclusion, and linkage disequilibrium of IgG3-IgG1. Increased number of homozygous GM-specific IgG subclass genotypes with total loss of alternative IgG subclass molecules, inborn errors of immunity (IEI), are found in severe immunological diseases. METHODS: A novel ELISA using GM-specific myeloma proteins and GM-specific monoclonals, identifies 6 alternative GM-specific IgG subclass genes and molecules IgG3*b & IgG3*g, IgG1*f & IgG1*a and IgG2*n & IgG2*-n, with different structures and functions. 4 different IgG3-IgG1-IgG2 haplotypes encode 10 individual IGHG diplotypes from 10 innate lymphoid combined B cells in 587 healthy. RESULTS: The alternative GM-specific IgG subclass genes have different structures and functions and respond differently in immunotherapy to antigen stimulation with virus, bacteria and allergens. In this report we focus on excluded GM-IgG subclass genes, inborn errors of immunity (IEI) dominating in severe immunological diseases, severe infections, primary immunodeficiencies (PIDs), JCA, asthma, diabetes type 1 and malignancy. By intravenous immunoglobulins (IVIG) the excluded IgG subclass molecules are supplied and may prevent primary virus attacks and exacerbations in autoimmune disorders. IgG subclass genes orchestrate additional immune factors of inflammation. CONCLUSION: Excluded GM-specific IgG subclass genes, IEI explore diagnosis, pathogenesis, prognosis and different phenotypes in immunological diseases, with IVIG as treatment. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494059","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":"Posttransplant B cell Development and Function in Patients with B cell Positive SCID Caused by Pathogenic Variants in IL2RG and JAK3.","authors":"Eva-Maria Jacobsen, Abdallah Khazaleh, Kerstin Felgentreff, Ingrid Furlan, Katharina Wustrau, Mehtap Sirin, Holger Cario, Benjamin Mayer, Ulrich Pannicke, Klaus Schwarz, Klaus-Michael Debatin, Wilhelm Friedrich, Ansgar S Schulz, Manfred Hoenig","doi":"10.1007/s10875-026-02004-2","DOIUrl":"10.1007/s10875-026-02004-2","url":null,"abstract":"<p><p>Genetic defects in IL2RG or JAK3 can cause the phenotype of severe combined immunodeficiency (SCID) with absent T- and non-functional B-lymphocytes (T-B+ SCID). B cell function and the need for immunoglobulin replacement therapy after hematopoietic stem cell transplantation (HSCT) depends on the engraftment of donor B-lymphocytes. In a retrospective study we describe B-lymphocyte reconstitution after HSCT with the aim to identify B cell subpopulations as an early predictor for the maturation and function of B cells after HSCT. All patients included underwent HSCT in a single institution between 1980 and 2017. First, we studied B cell maturation in cryopreserved blood samples of 12 patients with B+ SCID (IL2RG-deficiency) after haploidentical HSCT presenting with mixed B cell chimerism. Recipient and donor B cell subpopulations were identified by HLA-staining using flow cytometry. In a consecutive step we compared B cell subpopulations irrespective of chimerism between patients with or without post-transplant B cell function. Samples for this study were obtained between day + 90 to + 250 after HSCT from 25 post-transplant long-term survivors with B-positive SCID (9 with genetic variants in JAK3, 16 in IL2RG), 9/25 were dependent and 16/25 independent of immunoglobulin (Ig) -substitution.We demonstrate that a proportion of less than 2% of donor B cells can be sufficient for posttransplant B cell function and that a proportion of more than 4.7% of switched memory (IgM-) B cells in the memory B cell population (CD19 + CD27+) between days + 90 and + 250 after HSCT correlates with normal B cell function and independence from immunoglobulin substitution.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494056","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":"Fostamatinib Dual Immunomodulation in Post-Haploidentical HSCT Autoimmune Cytopenia and Autoimmune Hepatitis: A Case Report and Review of Literature.","authors":"Antimo Tessitore, Debora Curci, Aurelio Sonzogni, Martina Franzin, Giulia Schillani, Anna Flamigni, Gilda Paternuosto, Natalia Maximova","doi":"10.1007/s10875-026-02005-1","DOIUrl":"10.1007/s10875-026-02005-1","url":null,"abstract":"<p><p>PURPOSE: To describe the effectiveness and safety of fostamatinib off-label use in a pediatric patient with autoimmune cytopenia and autoimmune hepatitis following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We report the detailed changes in clinical, histopathological, and cytokine profiling in a pediatric HSCT recipient during treatment with fostamatinib. RESULTS: Fostamatinib administration was well-tolerated with no adverse events observed, leading to sustained hematological recovery and a significant improvement in liver enzyme levels. Histological features confirmed the complete remission of autoimmune hepatitis. Cytokine profiling demonstrated substantial normalization of pro-inflammatory markers, downregulated at onset. CONCLUSION: Fostamatinib demonstrated a dual benefit in resolving autoimmune cytopenia and immune-mediated liver inflammation, supporting its potential as a therapeutic option for immune dysregulation following allogeneic HSCT. </p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494088","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}