Journal of Clinical Immunology最新文献

{"title":"Successful Haematopoietic Stem Cell Transplantation for LRBA Deficiency with Fludarabine, Treosulfan, and Thiotepa-Based Conditioning","authors":"Bella Shadur, Adeeb NasserEddin, Irina Zaidman, Yael Dinur Schejter, Ehud Even-Or, Yackov Berkun, Isabelle Meyts, Hatem Hmedat, Ashraf Sulaiman, Stuart G. Tangye, Polina Stepensky","doi":"10.1007/s10875-024-01770-1","DOIUrl":"https://doi.org/10.1007/s10875-024-01770-1","url":null,"abstract":"<p>LRBA deficiency is an inborn error of immunity defined by autoimmunity, lymphoproliferation, recurrent infections, cytopenia, and inflammatory bowel disease. Despite recent advances in managing this disease with targeted biologic therapy, haematopoietic stem cell transplant (HSCT) remains the only cure. However, great variability exists between protocols used to transplant patients with LRBA deficiency. We describe a cohort of seven patients with LRBA deficiency who underwent HSCT using a myeloablative, reduced toxicity regime of fludarabine, treosulfan, and thiotepa at two transplantation centres from 2016 to 2019. Data were collected both retrospectively and prospectively, measuring time to engraftment, infectious complications, incidence of graft versus host disease, and post-transplantation chimerism. Six of seven patients survived transplantation, and four of six surviving patients achieving treatment-free survival. We thus recommend that HSCT with fludarabine, treosulfan, and thiotepa-based conditioning be considered in patients with LRBA deficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"21 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212568","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":"HSCT in a Patient with Cernunnos/XLF Deficiency and Omenn Syndrome","authors":"Marwa Chbihi, Léa Nabhan, Antoine Pinton, Philippe Drabent, Jean-Pierre de Villartay, Bénédicte Neven","doi":"10.1007/s10875-024-01765-y","DOIUrl":"https://doi.org/10.1007/s10875-024-01765-y","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"22 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212570","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":"Successful Long-Term Enzyme Replacement Therapy in a Patient with Delayed-Onset ADA Deficiency","authors":"Vasil Toskov, Pawan Bali, Michael S. Hershfield, Stephan Ehl, Carsten Speckmann","doi":"10.1007/s10875-024-01794-7","DOIUrl":"https://doi.org/10.1007/s10875-024-01794-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"48 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212573","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":"Abnormal Immune Profile in Individuals with Kabuki Syndrome","authors":"Margot Comel, Norma Saad, Debapratim Sil, Florence Apparailly, Marjolaine Willems, Farida Djouad, Jean-Christophe Andrau, Claire Lozano, David Genevieve","doi":"10.1007/s10875-024-01796-5","DOIUrl":"https://doi.org/10.1007/s10875-024-01796-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (<i>N</i> = 18) of individuals with Kabuki syndrome.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>All 18 individuals underwent genetic analysis: 15 had a variant in <i>KMT2D</i> and 3 a variant in <i>KDM6A</i>. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the <i>KMT2D</i> truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"28 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212572","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":"Hyperferritinemia Screening to Aid Identification and Differentiation of Patients with Hyperinflammatory Disorders","authors":"Hallie A. Carol, Adam S. Mayer, Michael S. Zhang, Vinh Dang, Jemy Varghese, Zachary Martinez, Corinne Schneider, Joy (Elizabeth) Baker, Paul Tsoukas, Edward M. Behrens, Randy Q. Cron, Caroline Diorio, Lauren A. Henderson, Grant Schulert, Pui Lee, Kate F. Kernan, Scott W. Canna","doi":"10.1007/s10875-024-01797-4","DOIUrl":"https://doi.org/10.1007/s10875-024-01797-4","url":null,"abstract":"<p>High ferritin is an important and sensitive biomarker for the various forms of hemophagocytic lymphohistiocytosis (HLH), a diverse and deadly group of cytokine storm syndromes. Early action to prevent immunopathology in HLH often includes empiric immunomodulation, which can complicate etiologic work-up and prevent collection of early/pre-treatment research samples. To address this, we instituted an alert system at UPMC Children’s Hospital where serum ferritin &gt; 1000 ng/mL triggered real-time chart review, assessment of whether the value reflected “inflammatory hyperferritnemia (IHF)”, and biobanking of remnant samples from consenting IHF patients. We extracted relevant clinical data; periodically measured serum total IL-18, IL-18 binding protein (IL-18BP), and CXCL9; retrospectively classified patients by etiology into infectious, rheumatic, or immune dysregulation; and subjected a subgroup of samples to a 96-analyte biomarker screen. 180 patients were identified, 30.5% of which had IHF. Maximum ferritin levels were significantly higher in patients with IHF than with either hemoglobinopathy or transplant, and highly elevated total IL-18 levels were distinctive to patients with Stills Disease and/or Macrophage Activation Syndrome (MAS). Multi-analyte analysis showed elevation in proteins associated with cytotoxic lymphocytes in all IHF samples when compared to healthy controls and depression of proteins such as ANGPT1 and VEGFR2 in samples from hyperferritinemic sepsis patients relative to non-sepsis controls. This real-time IFH screen proved feasible and efficient, validated prior observations about the specificity of IL-18, enabled early sample collection from a complex population, suggested a unique vascular biomarker signature in hyperferritinemic sepsis, and expanded our understanding of IHF heterogeneity.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"26 1","pages":""},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212569","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":"Severe Extrahematopoietic Manifestations in Complete STAT1 LOF after Successful Allogeneic HCT.","authors":"Friederike Frieß, Michael Flaig, Michael H Albert, Christoph Klein, Fabian Hauck","doi":"10.1007/s10875-024-01789-4","DOIUrl":"10.1007/s10875-024-01789-4","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"189"},"PeriodicalIF":7.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Clinical Phenotype with CD79A Mutation and Refractory Helicobacter Bilis Infection.","authors":"Archan Sil, Suprit Basu, Kanika Arora, Raju Khubchandani, Amit Rawat, Deepti Suri","doi":"10.1007/s10875-024-01792-9","DOIUrl":"10.1007/s10875-024-01792-9","url":null,"abstract":"<p><p>Autosomal recessive agammaglobulinemia is a severe primary antibody deficiency disorder typically presenting in infancy. We present a rare case of an 8-year-old boy with AR agammaglobulinemia due to a homozygous splice site variant (c.499-1G > A) in the CD79A gene. Despite monthly intravenous immunoglobulin replacement and prophylactic antibiotics, he developed refractory Helicobacter bilis leg ulcers. Helicobacter species are known for extracellular colonization and are challenging to culture, necessitating molecular diagnostics for identification. The patient required prolonged treatment with intravenous meropenem followed by oral metronidazole and doxycycline for resolution of the ulcers over two years. The patient also exhibited persistent asymptomatic thrombocytopenia, an atypical finding in CD79A mutation cases. This case underscores the importance of genetic diagnosis and targeted antimicrobial therapy in managing rare infections associated with primary immunodeficiencies like autosomal recessive agammaglobulinemia due to CD79A mutation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"187"},"PeriodicalIF":7.2,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107943","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":"Novel EXTL3 Variants Causing Neuro-Immuno-Skeletal Dysplasia.","authors":"Sarah S Mehta, Marita Bosticardo, Luigi D Notarangelo, Maleewan Kitcharoensakkul","doi":"10.1007/s10875-024-01784-9","DOIUrl":"10.1007/s10875-024-01784-9","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"188"},"PeriodicalIF":7.2,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107944","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":"Racial Disparities in the Diagnosis of Inborn Errors of Immunity.","authors":"Patrick O'Connell, O'Jay Stewart, Dusan Bogunovic","doi":"10.1007/s10875-024-01790-x","DOIUrl":"10.1007/s10875-024-01790-x","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"186"},"PeriodicalIF":7.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107945","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":"Hereditary C1q Deficiency is Associated with Type 1 Interferon-Pathway Activation and a High Risk of Central Nervous System Inflammation.","authors":"Clément Triaille, Neha Mohan Rao, Gillian I Rice, Luis Seabra, Fraser J H Sutherland, Vincent Bondet, Darragh Duffy, Andrew R Gennery, Benjamin Fournier, Brigitte Bader-Meunier, Christopher Troedson, Gavin Cleary, Helena Buso, Jacqueline Dalby-Payne, Prajakta Ranade, Katrien Jansen, Lien De Somer, Marie-Louise Frémond, Pallavi Pimpale Chavan, Melanie Wong, Russell C Dale, Carine Wouters, Pierre Quartier, Raju Khubchandani, Yanick J Crow","doi":"10.1007/s10875-024-01788-5","DOIUrl":"10.1007/s10875-024-01788-5","url":null,"abstract":"<p><p>Hereditary C1q deficiency (C1QDef) is a rare monogenic disorder leading to defective complement pathway activation and systemic lupus erythematosus (SLE)-like manifestations. The link between impairment of the complement cascade and autoimmunity remains incompletely understood. Here, we assessed type 1 interferon pathway activation in patients with C1QDef. Twelve patients with genetically confirmed C1QDef were recruited through an international collaboration. Clinical, biological and radiological data were collected retrospectively. The expression of a standardized panel of interferon stimulated genes (ISGs) in peripheral blood was measured, and the level of interferon alpha (IFNα) protein in cerebrospinal fluid (CSF) determined using SIMOA technology. Central nervous system (encompassing basal ganglia calcification, encephalitis, vasculitis, chronic pachymeningitis), mucocutaneous and renal involvement were present, respectively, in 10, 11 and 2 of 12 patients, and severe infections recorded in 2/12 patients. Elevated ISG expression was observed in all patients tested (n = 10/10), and serum and CSF IFNα elevated in 2/2 patients. Three patients were treated with Janus-kinase inhibitors (JAKi), with variable outcome; one displaying an apparently favourable response in respect of cutaneous and neurological features, and two others experiencing persistent disease despite JAKi therapy. To our knowledge, we report the largest original series of genetically confirmed C1QDef yet described. Additionally, we present a review of all previously described genetically confirmed cases of C1QDef. Overall, individuals with C1QDef demonstrate many characteristics of recognized monogenic interferonopathies: particularly, cutaneous involvement (malar rash, acral vasculitic/papular rash, chilblains), SLE-like disease, basal ganglia calcification, increased expression of ISGs in peripheral blood, and elevated levels of CSF IFNα.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 8","pages":"185"},"PeriodicalIF":7.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080503","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}