425 results match your criteria Lymphoproliferative Syndrome X-linked


Fatal SARS in X-Linked Lymphoproliferative Disease Type 1: A Case Report.

Front Pediatr 2022 14;10:794110. Epub 2022 Apr 14.

Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.

X-linked lymphoproliferative disease (XLP1) is an inborn error of immunity (IEI) with severe immune dysregulation caused by a mutation in the gene resulting in the absence or dysfunction of signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). The severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (CoV), a highly pathogenic CoV, has been shown to only cause mild diseases in Asian children. We report on a 5-year-old Nepalese boy with agammaglobulinemia and probable SARS who died of diffuse alveolar damage 22 days after admission amid the SARS outbreak. Read More

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Case Report: Atypical Manifestations Associated With FOXP3 Mutations. The "Fil Rouge" of Treg Between IPEX Features and Other Clinical Entities?

Front Immunol 2022 11;13:854749. Epub 2022 Apr 11.

Unitá Operativa (UO) of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Introduction: The Forkhead box protein P3 (FOXP3) is a transcription factor central to the function of regulatory T cells (Treg). Mutations in the gene lead to a systemic disease called immune dysregulation, polyendocrinopathy, and enteropathy, an X-linked syndrome (IPEX) characterized by the triad of early-onset intractable diarrhea, type 1 diabetes, and eczema. An atypical presentation of IPEX has been reported. Read More

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Case Report: Novel Splicing Variant in in a Patient With X-Linked Lymphoproliferative Syndrome Type 1.

Front Pediatr 2022 23;10:812590. Epub 2022 Mar 23.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

X-linked lymphoproliferative disease type 1 (XLP1), an X-linked recessive genetic disorder, is associated with primary immunodeficiency. Patients with XLP1 are susceptible to Epstein-Barr virus (EBV) infection. gene is known as the causative gene. Read More

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Preemptive hematopoietic cell transplantation for asymptomatic patients with X-linked lymphoproliferative syndrome type 1.

Clin Immunol 2022 04 30;237:108993. Epub 2022 Mar 30.

Deparment of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address:

Few reports have examined whether prophylactic allogeneic hematopoietic cell transplantation (HCT) for X-linked lymphoproliferative syndrome type 1 (XLP1) improves the prognosis. We compared the prognosis of symptomatic probands and affected siblings in the same family. Twenty-two cases (10 probands and 12 affected siblings) in Japan, the United Kingdom, and the United States were analyzed. Read More

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Rheumatologic diseases in patients with inborn errors of immunity in the USIDNET registry.

Clin Rheumatol 2022 Jan 31. Epub 2022 Jan 31.

Department of Pediatrics, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.

There is a gap in clinical knowledge regarding associations between specific inborn errors of immunity (IEIs) and rheumatologic diseases. This study reports the frequency of rheumatologic conditions in a large cohort of patients with IEI using the USIDNET (United States Immunodeficiency Network) registry. We used the USIDNET registry to conduct the analysis. Read More

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January 2022

Exon skipping caused by a complex structural variation in SH2D1A resulted in X-linked lymphoproliferative syndrome type 1.

Mol Genet Genomic Med 2022 03 29;10(3):e1873. Epub 2022 Jan 29.

Department of Neurology, Hunan Children 's Hospital, Changsha, P.R. China.

Background: X-linked lymphoproliferative syndrome type 1 (XLP1) is a rare primary immunodeficiency disorder characterized by severe immune dysregulation often after viral infection. It is caused by hemizygous mutations in the X-linked SH2D1A gene. People with XLP1 have complex and variable phenotype manifestations as EBV-driven severe or fulminant mononucleosis, hemophagocytic lymphohistiocytosis (EBV-HLH), dysgammaglobulinemia, and B-cell lymphoma. Read More

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Diagnosis of HLH: two siblings, two distinct genetic causes.

Clin Exp Immunol 2022 Apr;207(2):205-207

Immunology Laboratory, Great Ormond Street Hospital, London, UK.

This report highlights case of two siblings who developed haemophagocytic lymphohystiocytosis due to distinct genetic abnormalities. Though their presentation was clinically similar, the cases demonstrate that a shared genetic diagnosis among siblings cannot be assumed. Read More

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Identification of Germline Non-coding Deletions in XIAP Gene Causing XIAP Deficiency Reveals a Key Promoter Sequence.

J Clin Immunol 2022 04 9;42(3):559-571. Epub 2022 Jan 9.

Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Imagine Institute, Paris, France.

Purpose: X-linked inhibitor of apoptosis protein (XIAP) deficiency, also known as the X-linked lymphoproliferative syndrome of type 2 (XLP-2), is a rare immunodeficiency characterized by recurrent hemophagocytic lymphohistiocytosis, splenomegaly, and inflammatory bowel disease. Variants in XIAP including missense, non-sense, frameshift, and deletions of coding exons have been reported to cause XIAP deficiency. We studied three young boys with immunodeficiency displaying XLP-2-like clinical features. Read More

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Paneth cell dysfunction and the intestinal microbiome in XIAP deficiency.

Sci Immunol 2021 Nov 5;6(65):eabm0293. Epub 2021 Nov 5.

Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.

New data suggest how epithelial dysfunction and intestinal dysbiosis contribute to inflammatory bowel disease in patients and in models of XIAP deficiency (see the related Research Articles by Strigli . and Wahida .). Read More

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November 2021

XIAP restrains TNF-driven intestinal inflammation and dysbiosis by promoting innate immune responses of Paneth and dendritic cells.

Sci Immunol 2021 Nov 5;6(65):eabf7235. Epub 2021 Nov 5.

Cell Death and Inflammation Unit, VIB-Center for Inflammation Research (IRC), VIB, Ghent, Belgium.

Deficiency in X-linked inhibitor of apoptosis protein (XIAP) is the cause for X-linked lymphoproliferative syndrome 2 (XLP2). About one-third of these patients suffer from severe and therapy-refractory inflammatory bowel disease (IBD), but the exact cause of this pathogenesis remains undefined. Here, we used XIAP-deficient mice to characterize the mechanisms underlying intestinal inflammation. Read More

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November 2021

Molecular Genetics Diversity of Primary Hemophagocytic Lymphohistiocytosis among Polish Pediatric Patients.

Arch Immunol Ther Exp (Warsz) 2021 Oct 22;69(1):31. Epub 2021 Oct 22.

Department of Pediatrics, Hematology and Oncology, Medical University of Warsaw, Żwirki i Wigury 63A, 02-091, Warsaw, Poland.

Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of life-threatening inflammation caused by an excessive, prolonged and ineffective immune response. An increasing number of HLH cases is recognized in Poland, but the genetic causes of familial HLH (FHL) have not been reported. We investigated the molecular genetics and associated outcomes of pediatric patients who met HLH criteria. Read More

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October 2021

Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD.

J Clin Immunol 2022 01 29;42(1):36-45. Epub 2021 Sep 29.

Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.

X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Read More

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January 2022

X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children-A Case Report.

Front Pediatr 2021 3;9:691024. Epub 2021 Aug 3.

Division of Immunology, University Children's Hospital Zurich, Zurich, Switzerland.

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called (MIS-C) or (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Read More

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Hematopoietic Cell Transplantation Rescues Inflammatory Bowel Disease and Dysbiosis of Gut Microbiota in XIAP Deficiency.

J Allergy Clin Immunol Pract 2021 10 8;9(10):3767-3780. Epub 2021 Jul 8.

Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address:

Background: X-linked inhibitor of apoptosis protein (XIAP) deficiency is an infrequent inborn error of immunity that is often associated with refractory inflammatory bowel disease (IBD). The natural course of XIAP deficiency is typically associated with poor prognosis, and hematopoietic cell transplantation (HCT) is the only curative treatment.

Objective: To study (1) the effect of HCT on patients with XIAP deficiency undergoing HCT, (2) the status of XIAP deficiency-associated IBD after HCT, and (3) the gut microbiota of XIAP deficiency-associated IBD before and after HCT. Read More

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October 2021

Haemophagocytic lymphohistiocytosis and Epstein-Barr virus: a complex relationship with diverse origins, expression and outcomes.

Br J Haematol 2022 01 24;196(1):31-44. Epub 2021 Jun 24.

Department of Paediatrics, Baylor College of Medicine, Houston, TX, USA.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus with rare but severe potential for lymphoproliferative complications. EBV is associated with a variety of presentations of haemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening hyperinflammatory syndrome that can occur in patients with genetic defects associated with dysregulation of the immune response (familial HLH) or arise in patients with underlying infection or malignancy (non-familial or secondary HLH). Read More

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January 2022

Successful Salvage Haploidentical Bone Marrow Transplantation in a Child With Hemophagocytic Lymphohistiocytosis, When the Previously Matched Unrelated Donor Tested Positive for SARS-CoV-2 on the Day of Stem Cells Collection.

Transplant Proc 2021 Oct 27;53(8):2498-2501. Epub 2021 Apr 27.

Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland. Electronic address:

The coronavirus disease 2019 pandemic has made us adjust our standards and cope with unpredictable circumstances affecting the whole world, including the medical field. A 2-year-old boy diagnosed with X-linked lymphoproliferative disease type 2 with concomitant positive polymerase chain reaction test for Epstein-Barr virus-DNA was admitted to our transplant ward. His treatment scheme had to be modified at the last moment because of a donor disqualification due to a positive polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 just before the apheresis. Read More

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October 2021

Infection-induced inflammation from specific inborn errors of immunity to COVID-19.

FEBS J 2021 09 20;288(17):5021-5041. Epub 2021 May 20.

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

Inborn errors of immunity (IEIs) are a group of genetically defined disorders leading to defective immunity. Some IEIs have been linked to mutations of immune receptors or signaling molecules, resulting in defective signaling of respective cascades essential for combating specific pathogens. However, it remains incompletely understood why in selected IEIs, such as X-linked lymphoproliferative syndrome type 2 (XLP-2), hypo-immune response to specific pathogens results in persistent inflammation. Read More

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September 2021

Preimplantation Genetic Testing for a Chinese Family With X-Linked Lymphoproliferative Syndrome Type 1.

Front Genet 2020 4;11:550507. Epub 2020 Nov 4.

The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency disorder. We performed experiments based on two strategies of preimplantation genetic testing (PGT) for a family with XLP caused by a mutation in (c.191G > A). Read More

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November 2020

T cell gene therapy to treat immunodeficiency.

Br J Haematol 2021 02 10;192(3):433-443. Epub 2020 Sep 10.

Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK.

The application of therapeutic T cells for a number of conditions has been developed over the past few decades with notable successes including donor lymphocyte infusions, virus-specific T cells and more recently CAR-T cell therapy. Primary immunodeficiencies are monogenetic disorders leading to abnormal development or function of the immune system. Haematopoietic stem cell transplantation and, in specific candidate diseases, haematopoietic stem cell gene therapy has been the only definitive treatment option so far. Read More

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February 2021

[Lymphoproliferative disorders and inborn errors of immunity].

Rinsho Ketsueki 2020 ;61(9):1365-1372

Department of Pediatrics, Hiroshima University Institute of Biomedical and Health Sciences.

Lymphoproliferative disease (LPD) is a comprehensive concept covering diseases ranging from transient lymphadenopathy to lymphoma. LPD is frequently associated with Epstein-Barr virus (EBV) infections and tends to occur in patients with inborn errors of immunity (IEI) and in patients after organ transplantation. Most patients with severe combined immunodeficiency or X-linked lymphoproliferative disease develop LPD. Read More

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January 2021

Epstein-Barr virus-associated lymphocytic cholangitis in a child with X-linked lymphoproliferative syndrome.

Scand J Immunol 2021 Feb 23;93(2):e12975. Epub 2020 Sep 23.

Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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February 2021

Hemophagocytic lymphohistiocytosis secondary to X-linked lymphoproliferative syndrome type 2.

Med Clin (Barc) 2021 08 18;157(4):207-208. Epub 2020 Aug 18.

Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, España.

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A novel pathogenic SH2D1A mutation for X-linked lymphoproliferative syndrome type 1.

Clin Immunol 2020 10 10;219:108569. Epub 2020 Aug 10.

Division of Allergy Immunology and Dermatology, Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada.

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October 2020

Expanding clinical spectrum of female X-linked lymphoproliferative syndrome 2.

Pediatr Blood Cancer 2021 02 19;68(2):e28592. Epub 2020 Jul 19.

Division of Hematology/Oncology and Blood and Marrow Transplant Program, Children's Hospital of Michigan, Carman and Ann Adams Department of Pediatrics, Barbara Ann Karmanos Cancer Center, Central Michigan University College of Medicine, Detroit, Michigan.

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February 2021

[Clinical study of haploidentical hematopoietic stem cell transplantation on 15 cases of adult-onset primary hemophagocytic lymphohistiocytosis].

Zhonghua Xue Ye Xue Za Zhi 2020 Jun;41(6):511-516

Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

This study was designed to evaluate the efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for adult-onset primary hemophagocytic lymphohistiocytosis (HLH) . A retrospective study was carried out to analyze the clinical data of 15 adult patients with primary HLH who received haplo-HSCT from January 2013 to October 2019 in Beijing Friendship Hospital, Capital Medical University, Beijing, China. Among the 15 patients included in the study, ten were males and five were females, with a median age of 21 years old (18-52) . Read More

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Haploidentical Hematopoietic Stem Cell Transplantation for XIAP Deficiency: a Single-Center Report.

J Clin Immunol 2020 08 5;40(6):893-900. Epub 2020 Jul 5.

Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, P.R., China.

Purpose: X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in the XIAP/BIRC4 gene is a rare inherited primary immunodeficiency also known as X-linked lymphoproliferative syndrome type 2 (XLP2). Hematopoietic stem cell transplantation (HSCT) is currently the only curative strategy available. However, few studies of haploidentical HSCT have been published regarding the outcomes in patients with this syndrome. Read More

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Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease.

Cell Death Dis 2020 06 8;11(6):430. Epub 2020 Jun 8.

Department of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, V Uvalu 84, Prague, Czech Republic.

X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2-dependent NFκB and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and severe primary immunodeficiency known as X-linked lymphoproliferative syndrome type 2 (XLP-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and inflammatory bowel disease (IBD), usually with very early onset. Here, we present a novel XIAP mutation identified in a patient with atypical adult-onset IBD complicated by relapsing HLH, splenomegaly and sarcoid-like disease. Read More

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