Journal of Clinical Immunology最新文献

{"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":"https://doi.org/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":null,"pages":null},"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":"https://doi.org/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":null,"pages":null},"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":"https://doi.org/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":null,"pages":null},"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":"https://doi.org/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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"Levels of Natural Antibodies Before and After Immunoglobulin Replacement Treatment Affect the Clinical Phenotype in Common Variable Immunodeficiency.","authors":"Ioannis Sarrigeorgiou, Gerasimina Tsinti, Fani Kalala, Anastasios Germenis, Matthaios Speletas, Peggy Lymberi","doi":"10.1007/s10875-024-01805-7","DOIUrl":"10.1007/s10875-024-01805-7","url":null,"abstract":"<p><p>Natural antibodies (NAbs) occurring in individuals without prior exposure to specific antigens, provide direct first barrier protection against pathogens, and exert immunoregulation thus actively contributing to the maintenance of immune homeostasis, controlling inflammatory processes and preventing autoimmunity. Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by a compromised immune function that brings into focus the role of NAbs. Our aim was to explore whether NAb levels could serve as potential key indicators in CVID for monitoring disease progression and predicting outcomes. In this study, we analyzed a Hellenic cohort of 56 patients with CVID (31 newly diagnosed and 25 under immunoglobulin replacement therapy-IgRT) and 33 healthy controls, for total Ig levels and serum IgM and IgG NAb levels against five informative target-antigens of NAbs, namely, actin, DNA, carbonic anhydrase, F(ab΄)₂ fragments of human IgG and TriNitroPhenyl. In addition, follow-up pre- and post- IgRT samples were analyzed in ten (10) patients of our cohort. Results showed that Ig-treated patients exhibited significantly lower IgM NAb levels than untreated patients and healthy controls against all panel antigens. In the follow-up samples, pre-treatment IgM NAb levels negatively correlated with total serum IgM. This imbalance was only partially restored after IgRT, with a significant decrease in IgM NAb levels observed in nine out of ten patients. Moreover, post-treatment patients with recurrent infections presented significantly lower IgM NAb levels, a reduction also observed in patients with bronchiectasis independently of treatment status. On the contrary, post-treatment patients with enteropathy had significantly higher IgM NAb levels against all panel antigens, an increase also noted in patients with autoimmune diseases. Regarding IgG NAbs, replacement therapy restored levels to those of healthy controls. In conclusion, impaired NAb levels are found in CVID patients, particularly related to certain phenotypes. Moreover, the significant decrease in IgM NAb levels after IgRT suggests a potential association with disease course and complications. The results suggest that administration of human IgM NAbs may be an effective combinatorial treatment in selected patients. Further research is needed to understand the functional roles of NAbs in CVID and its complex clinical phenotypes.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288345","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":"Machine Learning of Laboratory Data in Predicting 30-Day Mortality for Adult Hemophagocytic Lymphohistiocytosis.","authors":"Jun Zhou, Mengxiao Xie, Ning Dong, Mingjun Xie, Jingping Liu, Min Wang, Yaman Wang, Hua-Guo Xu","doi":"10.1007/s10875-024-01806-6","DOIUrl":"https://doi.org/10.1007/s10875-024-01806-6","url":null,"abstract":"<p><strong>Background: </strong>Hemophagocytic Lymphohistiocytosis (HLH) carries a high mortality rate. Current existing risk-evaluation methodologies fall short and improved predictive methods are needed. This study aimed to forecast 30-day mortality in adult HLH patients using 11 distinct machine learning (ML) algorithms.</p><p><strong>Methods: </strong>A retrospective analysis on 431 adult HLH patients from January 2015 to September 2021 was conducted. Feature selection was executed using the least absolute shrinkage and selection operator. We employed 11 ML algorithms to create prediction models. The area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, F1 score, calibration curve and decision curve analysis were used to evaluate these models. We assessed feature importance using the SHapley Additive exPlanation (SHAP) approach.</p><p><strong>Results: </strong>Seven independent predictors emerged as the most valuable features. An AUC between 0.65 and 1.00 was noted among the eleven ML algorithms. The gradient boosting decision tree (GBDT) algorithms demonstrated the most optimal performance (1.00 in the training cohort and 0.80 in the validation cohort). By employing the SHAP method, we identified the variables that contributed to the model and their correlation with 30-day mortality. The AUC of the GBDT algorithms was the highest when using the top 4 (ferritin, UREA, age and thrombin time (TT)) features, reaching 0.99 in the training cohort and 0.83 in the validation cohort. Additionally, we developed a web-based calculator to estimate the risk of 30-day mortality.</p><p><strong>Conclusions: </strong>With GBDT algorithms applied to laboratory data, accurate prediction of 30-day mortality is achievable. Integrating these algorithms into clinical practice could potentially improve 30-day outcomes.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288346","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":"Correction to: A Novel Case of IFNAR1 Deficiency Identified a Common Canonical Splice Site Variant in DOCK8 in Western Polynesia: The Importance of Validating Variants of Unknown Significance in Under-Represented Ancestries.","authors":"Aimee Huynh, Paul E Gray, Anna Sullivan, Joseph Mackie, Antoine Guerin, Geetha Rao, Karrnan Pathmanandavel, Erika Della Mina, Georgina Hollway, Matthew Hobbs, Karen Enthoven, Patrick O'Young, Sam McManus, Luke H Wainwright, Megan Higgins, Fallon Noon, Melanie Wong, Paul Bastard, Qian Zhang, Jean-Laurent Casanova, Kuang-Chih Hsiao, Alberto Pinzon-Charry, Cindy S Ma, Stuart G Tangye","doi":"10.1007/s10875-024-01801-x","DOIUrl":"10.1007/s10875-024-01801-x","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288331","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":"Uniparental Disomy of Chromosome 4: A Case of Whole Chromosome UPD Presenting with LRBA Deficiency","authors":"Bilgesu Ak, Erhan Parıltay, Reyhan Gümüşburun, Ceyda Tunakan Dalgıç, Ayça Aykut, Asude Durmaz, Haluk Akın, Ömür Ardeniz, Bernice Lo","doi":"10.1007/s10875-024-01803-9","DOIUrl":"https://doi.org/10.1007/s10875-024-01803-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Lipopolysaccharide-responsive beige-like anchor protein (<i>LRBA</i>) encodes a widely expressed cytosolic protein that participates in polarized vesicle trafficking. Homozygous loss-of-function <i>LRBA</i> mutations can lead to immune deficiency due to the lack of immune regulation, classified as a part of Tregopathies. We present a case of a 49-year-old female, with polyarthralgia in metacarpophalangeal and proximal interphalangeal joints bilaterally, and morning stiffness, leading to the diagnosis of rheumatoid arthritis treated with pulse steroid therapy. She had experienced sepsis and in-depth scrutiny revealed panhypogammaglobulinemia. After being referred to the immunology clinic, she was followed under the diagnosis of common variable immunodeficiency (CVID)-like inborn errors of immunity (IEI).</p><h3 data-test=\"abstract-sub-heading\">Methods and Results</h3><p>Physical examination and diagnostic follow-up revealed massive splenomegaly accompanied by portal hypertension, and ulcerations in the colon. She also presented with periodic hematuria and dysuria. Cystoscopic biopsy revealed mast cell-derived interstitial cystitis which has not been previously reported in LRBA deficiency in the literature to our knowledge. A multi-gene next-generation sequencing panel performed for immune deficiencies (264 genes and 524 amplicons), resulted in the identification of an apparently homozygous <i>LRBA</i> mutation (p.Arg722His) in the Beige and Chediak-Higashi (BEACH) domain. The SNP array showed copy neutral absence of heterozygosity of the entire chromosome 4, which is consistent with uniparental isodisomy of chromosome 4.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In conclusion, this case study underscores the critical role of LRBA in immune regulation and highlights the clinical heterogeneity associated with LRBA deficiency. The patient’s presentation with severe immune dysregulation, including massive splenomegaly, portal hypertension, and the novel finding of mast cell-derived interstitial cystitis, expands the clinical spectrum of <i>LRBA</i> mutations. The identification of an apparently homozygous <i>LRBA</i> mutation via next-generation sequencing further emphasizes the importance of genetic analysis in diagnosing monogenic defects manifested as CVID-like phenotype. This is the first reported case of LRBA deficiency due to whole chromosome UPD to our knowledge. Future research should focus on elucidating the full range of clinical manifestations and developing targeted therapies for patients with LRBA deficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258145","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":"Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey","authors":"Hayrunnisa Bekis Bozkurt, Feyza Bayram Catak, Ali Sahin, Ezgi Yalcin Gungoren, Betul Gemici Karaarslan, Nalan Yakici, Melek Yorgun Altunbas, Mehmet Cihangir Catak, Salim Can, Razin Amirov, Selcen Bozkurt, Necmiye Ozturk, Sevgi Bilgic Eltan, Nurhan Kasap, Fatma Bal Cetinkaya, Fazil Orhan, Mustafa Arga, Ozlem Cavkaytar, Ayca Kiykim, Elif Karakoc-Aydiner, Ahmet Ozen, Safa Baris","doi":"10.1007/s10875-024-01791-w","DOIUrl":"https://doi.org/10.1007/s10875-024-01791-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic <i>FOXP3</i> variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cT_FH) cells, and T-cell proliferation were analyzed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the T_H2-like skewing accompanied by reduced T_H17-like responses was observed in cT_FH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269228","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}