The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Arndt Borkhardt - One of the best experts on this subject based on the ideXlab platform.
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interleukin 2 inducible t cell kinase deficiency new patients new insight
Frontiers in Immunology, 2018Co-Authors: Sujal Ghosh, Ingo Drexler, Sanil Bhatia, Heiko Adler, Andrew R. Gennery, Arndt BorkhardtAbstract:Patients with primary immunodeficiency can be prone to severe Epstein-Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the Interleukin-2 inducible T-cell kinase (ITK) gene experience Hodgkin and Non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis and Dysgammaglobulinemia. In this review we give an update on further reported patients. We believe that current clinical data advocate early definitive treatment by hematopoietic stem cell transplantation, as transplant outcome in primary immunodeficiency disorders in general has gradually improved in recent years. Furthermore, we summarize experimental data in the murine model to provide further insight of pathophysiology in ITK deficiency.
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Interleukin-2-Inducible T-Cell Kinase Deficiency—New Patients, New Insight?
Frontiers Media S.A., 2018Co-Authors: Sujal Ghosh, Ingo Drexler, Sanil Bhatia, Heiko Adler, Andrew R. Gennery, Arndt BorkhardtAbstract:Patients with primary immunodeficiency can be prone to severe Epstein–Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the interleukin-2-inducible T-cell kinase (ITK) gene experience Hodgkin and non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis, and Dysgammaglobulinemia. In this review, we give an update on further reported patients. We believe that current clinical data advocate early definitive treatment by hematopoietic stem cell transplantation, as transplant outcome in primary immunodeficiency disorders in general has gradually improved in recent years. Furthermore, we summarize experimental data in the murine model to provide further insight of pathophysiology in ITK deficiency
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Interleukin-2-Inducible T-Cell Kinase (ITK) Deficiency - Clinical and Molecular Aspects
Journal of Clinical Immunology, 2014Co-Authors: Sujal Ghosh, Kirsten Bienemann, Kaan Boztug, Arndt BorkhardtAbstract:In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma, lymphoproliferative disease (LPD), lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis (HLH) and Dysgammaglobulinemia. Several newly discovered primary immunodeficiencies ( STK4, CD27, MAGT1, CORO1A ) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase ( ITK ) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model.
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KEY REVIEWARTICLE Interleukin-2-Inducible T-Cell Kinase (ITK) Deficiency- Clinical and Molecular Aspects
2014Co-Authors: Sujal Ghosh, Kirsten Bienemann, Kaan Boztug, Arndt BorkhardtAbstract:Abstract In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysreg-ulation manifesting as fatal mononucleosis, lymphoma, lym-phoproliferative disease (LPD), lymphomatoid granulomato-sis, hemophagocytic lymphohistiocytosis (HLH) and Dysgammaglobulinemia. Several newly discovered primary immunodeficiencies (STK4, CD27, MAGT1, CORO1A) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase (ITK) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model
Bodo Grimbacher - One of the best experts on this subject based on the ideXlab platform.
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Linkage of autosomal-dominant common variable immunodeficiency to chromosome 4q
EUR J HUM GENET, 2006Co-Authors: Bodo GrimbacherAbstract:The phenotype of common variable immunodeficiency (CVID) is characterized by recurrent infections owing to hypogammaglobulinemia, with deficiency in immunoglobulin (Ig) G and at least one of IgA or IgM. Family studies have shown a genetic association between CVID and selective IgA deficiency (IgAD), the latter being a milder disorder compatible with normal health. Approximately 20-25% of CVID cases are familial, if one includes families with at least one case of CVID and one of IgAD. Nijenhuis et al described a five-generation family with six cases of CVID, five cases of IgAD, and three cases of Dysgammaglobulinemia. We conducted a genome-wide scan on this family seeking genetic linkage. One interval on chromosome 4q gives a peak multipoint LOD score of 2.70 using a strict model that treats only the CVID patients and one obligate carrier with Dysgammaglobulinemia as affected. Extending the definition of likely affected to include IgAD boosts the peak multipoint LOD score to 3.38. The linkage interval spans at least from D4S2361 to D4S1572. We extended our study to a collection of 32 families with at least one CVID case and a second case of either CVID or IgAD. We used the same dominant penetrance model and genotyped and analyzed nine markers on 4q. The 32 families have a peak multipoint LOD score under heterogeneity of 0.96 between markers D4S423 and D4S1572 within the suggested linkage interval of the first family, and an estimated proportion of linked families (a) of 0.32, supporting the existence of a disease-causing gene for autosomal-dominant CVID/IgAD on chromosome 4q.
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linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity
Human Genetics, 2003Co-Authors: D U Braig, Erikoliver Glocker, Ulrich Salzer, Klaus Warnatz, H H Peter, Alejandro A Schaffer, Bodo GrimbacherAbstract:Common variable immunodeficiency (CVID, OMIM 240500) and selective immunoglobulin A deficiency (IgAD) are the most frequent primary immunodeficiencies in humans. Of the cases with CVID/IgAD, 20%–25% are familial, but the only previous claims of linkage or association are to the HLA region on chromosome 6p. We report the results of a genome-wide scan in three multiplex families with CVID, IgAD, and Dysgammaglobulinemia, where affection is inherited in an autosomal dominant pattern. Two of the families are consistent with linkage to the telomeric region of chromosome 5p, whereas the third is consistent with linkage to the HLA region. Using a locus heterogeneity model and a conservative penetrance model, we obtained a LOD score of 3.35 for the 5p region. We sequenced the exons of one promising candidate gene within this region (PDCD6, also known as ALG-2) but found no causative mutation.
Sujal Ghosh - One of the best experts on this subject based on the ideXlab platform.
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interleukin 2 inducible t cell kinase deficiency new patients new insight
Frontiers in Immunology, 2018Co-Authors: Sujal Ghosh, Ingo Drexler, Sanil Bhatia, Heiko Adler, Andrew R. Gennery, Arndt BorkhardtAbstract:Patients with primary immunodeficiency can be prone to severe Epstein-Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the Interleukin-2 inducible T-cell kinase (ITK) gene experience Hodgkin and Non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis and Dysgammaglobulinemia. In this review we give an update on further reported patients. We believe that current clinical data advocate early definitive treatment by hematopoietic stem cell transplantation, as transplant outcome in primary immunodeficiency disorders in general has gradually improved in recent years. Furthermore, we summarize experimental data in the murine model to provide further insight of pathophysiology in ITK deficiency.
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Interleukin-2-Inducible T-Cell Kinase Deficiency—New Patients, New Insight?
Frontiers Media S.A., 2018Co-Authors: Sujal Ghosh, Ingo Drexler, Sanil Bhatia, Heiko Adler, Andrew R. Gennery, Arndt BorkhardtAbstract:Patients with primary immunodeficiency can be prone to severe Epstein–Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the interleukin-2-inducible T-cell kinase (ITK) gene experience Hodgkin and non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis, and Dysgammaglobulinemia. In this review, we give an update on further reported patients. We believe that current clinical data advocate early definitive treatment by hematopoietic stem cell transplantation, as transplant outcome in primary immunodeficiency disorders in general has gradually improved in recent years. Furthermore, we summarize experimental data in the murine model to provide further insight of pathophysiology in ITK deficiency
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Interleukin-2-Inducible T-Cell Kinase (ITK) Deficiency - Clinical and Molecular Aspects
Journal of Clinical Immunology, 2014Co-Authors: Sujal Ghosh, Kirsten Bienemann, Kaan Boztug, Arndt BorkhardtAbstract:In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysregulation manifesting as fatal mononucleosis, lymphoma, lymphoproliferative disease (LPD), lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis (HLH) and Dysgammaglobulinemia. Several newly discovered primary immunodeficiencies ( STK4, CD27, MAGT1, CORO1A ) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase ( ITK ) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model.
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KEY REVIEWARTICLE Interleukin-2-Inducible T-Cell Kinase (ITK) Deficiency- Clinical and Molecular Aspects
2014Co-Authors: Sujal Ghosh, Kirsten Bienemann, Kaan Boztug, Arndt BorkhardtAbstract:Abstract In patients with underlying immunodeficiency, Epstein-Barr virus (EBV) may lead to severe immune dysreg-ulation manifesting as fatal mononucleosis, lymphoma, lym-phoproliferative disease (LPD), lymphomatoid granulomato-sis, hemophagocytic lymphohistiocytosis (HLH) and Dysgammaglobulinemia. Several newly discovered primary immunodeficiencies (STK4, CD27, MAGT1, CORO1A) have been described in recent years; our group and collaborators were able to reveal the pathogenicity of mutations in the Interleukin-2-inducible T-cell Kinase (ITK) in a cohort of nine patients with most patients presenting with massive EBV B-cell lymphoproliferation. This review summarizes the clinical and immunological findings in these patients. Moreover, we describe the functional consequences of the mutations and draw comparisons with the extensively investigated function of ITK in vitro and in the murine model
Laurence Becker - One of the best experts on this subject based on the ideXlab platform.
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Measles Inclusion-Body Encephalitis Caused by the Vaccine Strain of Measles Virus
2016Co-Authors: Ari Bitnun, Patrick Shannon, Andrew Durward, Paul A Rota, William J Bellini, Caroline Graham, Elaine Wang, Laurence Becker, Margaret Fearon, Martin PetricAbstract:We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and Dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses. Neurological abnormalities associated with measles range from nonspecific electroencephalographic changes and CSF pleocytosis at the time of acute uncomplicated measles to more serious manifestations such as postinfectious enceph
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measles inclusion body encephalitis caused by the vaccine strain of measles virus
Clinical Infectious Diseases, 1999Co-Authors: Ari Bitnun, Patrick Shannon, Andrew Durward, Paul A Rota, William J Bellini, Caroline Graham, Elaine Wang, E L Fordjones, Peter Cox, Laurence BeckerAbstract:We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and Dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses.
Klaus Warnatz - One of the best experts on this subject based on the ideXlab platform.
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Follicular Helper T Cells in DiGeorge Syndrome.
Frontiers in immunology, 2018Co-Authors: Adam Klocperk, Klaus Warnatz, Zuzana Parackova, Marketa Bloomfield, Michal Rataj, Jan Pokorný, Susanne Unger, Anna SedivaAbstract:DiGeorge syndrome is an immunodeficiency characterized by thymic dysplasia resulting in T cell lymphopenia. Most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, such as autoimmune thrombocytopenia. B cells in DiGeorge syndrome show impaired maturation, with low switched-memory B cells and a wide spectrum of antibody deficiencies or Dysgammaglobulinemia, presumably due to impaired germinal center responses. We set out to evaluate circulating follicular helper T cells (cTFHs) in DiGeorge syndrome, as markers of T-B interaction in the germinal centers in a cohort of 17 patients with partial DiGeorge and 21 healthy controls of similar age. cTFHs were characterized as CXCR5+CD45RA- CD4+ T cells using flow cytometry. We verify previous findings that the population of memory CD4+ T cells is relatively increased in diGeorge patients, corresponding to low naive T cells and impaired T cell production in the thymus. The population of CXCR5+ memory CD4+ T cells (cTFHs) was significantly expanded in patients with DiGeorge syndrome, but only healthy controls and not DiGeorge syndrome patients showed gradual increase of CXCR5 expression on cTFHs with age. We did not observe correlation between cTFHs and serum IgG levels or population of switched memory B cells. There was no difference in cTFH numbers between DiGeorge patients with/without thrombocytopenia and with/without allergy. Interestingly, we show strong decline of PD1 expression on cTFHs in the first 5 years of life in DiGeorge patients and healthy controls, and gradual increase of PD1 and ICOS expression on CD4- T cells in healthy controls later in life. Thus, here, we show that patients with DiGeorge syndrome have elevated numbers of cTFHs, which, however, do not correlate with autoimmunity, allergy, or production of immunoglobulins. This relative expansion of cTFH cells may be a result of impaired T cell development in patients with thymic dysplasia.
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linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity
Human Genetics, 2003Co-Authors: D U Braig, Erikoliver Glocker, Ulrich Salzer, Klaus Warnatz, H H Peter, Alejandro A Schaffer, Bodo GrimbacherAbstract:Common variable immunodeficiency (CVID, OMIM 240500) and selective immunoglobulin A deficiency (IgAD) are the most frequent primary immunodeficiencies in humans. Of the cases with CVID/IgAD, 20%–25% are familial, but the only previous claims of linkage or association are to the HLA region on chromosome 6p. We report the results of a genome-wide scan in three multiplex families with CVID, IgAD, and Dysgammaglobulinemia, where affection is inherited in an autosomal dominant pattern. Two of the families are consistent with linkage to the telomeric region of chromosome 5p, whereas the third is consistent with linkage to the HLA region. Using a locus heterogeneity model and a conservative penetrance model, we obtained a LOD score of 3.35 for the 5p region. We sequenced the exons of one promising candidate gene within this region (PDCD6, also known as ALG-2) but found no causative mutation.