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1دورية أكاديمية
المؤلفون: Türkan Patıroğlu, Hatice Eke Güngör, Julie Sawalle Belohradsky, Ekrem Ünal, Christoph Klein
المصدر: Turkish Journal of Hematology, Vol 30, Iss 2, Pp 232-233 (2013)
مصطلحات موضوعية: leucocyte function disorders, myeloperoxidase, neutrophil, Diseases of the blood and blood-forming organs, RC633-647.5
العلاقة: https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-88557Test; https://doaj.org/toc/1308-5263Test; https://doaj.org/article/4e8d0e1b74bf4feda8794d21619b833bTest
الإتاحة: https://doi.org/10.4274/Tjh.2012.0012Test
https://doaj.org/article/4e8d0e1b74bf4feda8794d21619b833bTest -
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المؤلفون: Taco W. Kuijpers, Jörg Klepper, Roel P. Gazendam, Martin Herbst, Andreas H. Groll, Denise Reimnitz, Bernd Belohradsky, Johannes G. Liese, Paul-Gerhardt Schlegel, Julie Sawalle-Belohradsky, Bodo Grimbacher, Ellen D. Renner
المساهمون: Landsteiner Laboratory, Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology
المصدر: Pediatric infectious disease journal, 34(9), 999-1002. Lippincott Williams and Wilkins
مصطلحات موضوعية: Microbiology (medical), medicine.medical_specialty, Antifungal Agents, Turkey, CARD9 Gene, media_common.quotation_subject, Mutation, Missense, Candida albicans, medicine, Humans, Medical history, Girl, media_common, Genetics, biology, business.industry, Homozygote, Candidiasis, medicine.disease, biology.organism_classification, Dermatology, Meningitis, Fungal, CARD Signaling Adaptor Proteins, stomatognathic diseases, Treatment Outcome, Infectious Diseases, Child, Preschool, Pediatrics, Perinatology and Child Health, Mutation (genetic algorithm), Oral thrush, Drug Therapy, Combination, Female, Headaches, medicine.symptom, business, Meningitis
الوصف: A 4-year-old Turkish girl of consanguineous parents was hospitalized for the evaluation of headaches and recurrent febrile episodes of unknown origin. Her medical history was unremarkable except for a few episodes of uncomplicated oral thrush. Meningitis was diagnosed, and Candida albicans was the only pathogen identified by polymerase chain reaction and culture. Despite systemic antifungal multidrug therapy, a prolonged course of 16 months of therapy was necessary to clear C. albicans from the cerebrospinal fluid. Molecular genetic analysis revealed a homozygous caspase recruitment domain 9 (CARD9) mutation (Q295X), which was reported to predispose to chronic mucocutaneous candidiasis. Immunologic workup excluded predisposing B-cell and T-cell defects. In addition, T cells producing interleukin-17 were repeatedly measured within the normal range. Analyses of neutrophils demonstrated normal nicotinamide adenine dinucleotide phosphate oxidase activity in response to various stimuli including Staphylococcus aureus and C. albicans. Additional neutrophilic functional testing, however, showed a decreased cytotoxicity to nonopsonized C. albicans, indicating an impaired killing mechanism against Candida spp. independent from the production of reactive oxygen species by the nicotinamide adenine dinucleotide phosphate oxidase system. Because this defect was only demonstrated in the absence of opsonins, it might especially predispose to chronic C. albicans infections in the central nervous system where opsonin concentrations are usually low. We, therefore, suggest that due to an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the central nervous system.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1036d3b95b6d1a33ca9691731bdf401eTest
https://doi.org/10.1097/inf.0000000000000736Test -
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المؤلفون: M. Pinarci, Bernhard Przybilla, L. F. Schimke-Marques, A. Schlesinger, Valerie Heinz, D. Kreilinger, B. E. Halm, Bianca Schaub, Annette Boos, Julie Sawalle-Belohradsky, Beate Hagl, Ellen D. Renner, Benedikt D. Spielberger, Andreas Wollenberg, N. Ballenberger, Bernd H. Belohradsky
المصدر: Allergy. 69:943-953
مصطلحات موضوعية: Adult, Male, STAT3 Transcription Factor, medicine.medical_specialty, Allergy, DNA Mutational Analysis, Immunology, Context (language use), Immunoglobulin E, Dermatitis, Atopic, Young Adult, Food allergy, medicine, Guanine Nucleotide Exchange Factors, Humans, Immunology and Allergy, Eosinophilia, Sensitization, Skin Tests, Asthma, biology, business.industry, T-Lymphocytes, Helper-Inducer, Atopic dermatitis, Middle Aged, Flow Cytometry, medicine.disease, Dermatology, medicine.anatomical_structure, biology.protein, Female, medicine.symptom, business, Job Syndrome
الوصف: Background Increased serum IgE levels are characteristic but not specific for allergic diseases. Particularly, severe atopic dermatitis (AD) overlaps with hyper-IgE syndromes (HIES) regarding eczema, eosinophilia, and increased serum IgE levels. HIES are primary immunodeficiencies due to monogenetic defects such as in the genes DOCK8 and STAT3. As it is not known to date why allergic manifestations are not present in all HIES entities, we assessed the specificity of serum IgE of AD and HIES patients in the context of clinical and immunological findings. Methods Clinical data, skin prick tests, specific IgE to aero- and food allergens, and T helper (Th) subpopulations were compared in AD and molecularly defined HIES patients. Results Total serum IgE levels were similarly increased in STAT3-HIES, DOCK8-HIES, and AD patients. The ratio of aeroallergen-specific IgE to total IgE was highest in AD, whereas DOCK8-HIES patients showed the highest specific serum IgE against food allergens. Overall, clinical allergy and skin prick test results complied with the specific IgE results. Th2-cell numbers were significantly increased in DOCK8-HIES and AD patients compared to STAT3-HIES patients and controls. AD patients showed significantly higher nTreg-cell counts compared to STAT3-HIES and control individuals. High Th17-cell counts were associated with asthma. Specific IgE values, skin prick test, and T-cell subsets of STAT3-HIES patients were comparable with those of healthy individuals except decreased Th17-cell counts. Conclusion Hyper-IgE syndromes and atopic dermatitis patients showed different sensitization pattern of serum IgE corresponding to the allergic disease manifestations and Th-cell subset data, suggesting a key role of DOCK8 in the development of food allergy.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95a5bcf3cf325c65420d85b05a6ab12eTest
https://doi.org/10.1111/all.12416Test -
4دورية أكاديمية
المؤلفون: Toubiana, Julie, Okada, Satoshi, Hiller, Julia, Oleastro, Matias, Gomez, Macarena Lagos, Becerra, Juan Carlos Aldave, Ouachãe chardin, Marie, Fouyssac, Fanny, Girisha, Katta Mohan, Etzioni, Amos, Van Montfrans, Joris, Camcioglu, Yildiz, Kerns, Leigh Ann, Belohradsky, Bernd, Blanche, Stephane, Bousfiha, Aziz, Rodriguez gallego, Carlos, Meyts, Isabelle, Kisand, Kai, Reichenbach, Janine, Renner, Ellen D. , Rosenzweig, Sergio, Grimbacher, Bodo, Van De Veerdonk, Frank L. , Traidl hoffmann, Claudia, Picard, Capucine, Marodi, Laszlo, Morio, Tomohiro, Kobayashi, Masao, Lilic, Desa, Milner, Joshua D. , Holland, Steven, Casanova, Jean Laurent, Puel, Anne, Cypowyj, Sophie, Caroline Thumerelle, Antoine Toulon, Jacinta Bustamante, Natalia Tahuil, Aicha Salhi, Sorina Boiu, Charu Chopra, Daniela Di Giovanni, Liliana Bezrodnik, JeannetteBoutros, Caroline Thomas, Gina Lacuesta, Sarah Jannier, Anne-Sophie Korganow, Catherine Paillard, David Boutboul, M ́elanie Bu ́e, Aude Marie-Cardine, Sophie Bayart, Mélanie Migaud, Laurence Weiss, Marina Karmochkine, Juan-Miguel Garcia-Martinez, Jean-Louis Stephan, Philippe Bensaid, Guy-Patrick Jeannoel, Torsten Witte, Ulrich Baumann, Thomas Harrer, Carmen Navarrete, Antony Terance Benjamin, Davide Firinu, Claudio Pignata, Paolo Picco, David Mendoza, Saul Oswaldo Lugo Reyes, Carlos Torres Lozano, MargaritaOrtega-Cisneros, Mariana Cortina, Mehrnaz Mesdaghi, MohammadNabavi, Teresa Español, Maia Teresa Martinez- Saavedra, Nima Rezaei, Samaneh Zoghi, Malgorzata Pac, Vincent Barlogis, Gabriel Revon-Rivire, Yishai Haimi-Cohen, Ronen Spiegel, Dan Miron, Jabir Bouchaib, Lizbeth Blancas-Galicia, Beata Toth, Barbara Drexel, Pierre Simon Roherlich, Olivier Lesens, Miriam Hoernes, Elizabeth Drewe, Mario Abinum, Julie Sawalle-Belohradsky, Gerhard Kindle, Mark Depner, Lili Milani, Tiit Nikopensius, Maido Remm, Ulvi Gerst Talas, Mark Tucker, Mary Willis, Stephanie Leonard, Hilaire Meuwissen, Ronald M. Ferdman, Mark Wallace, Mukesh M. Desai, Prasad Taur, Raffaele Badolato, Beata Soltesz, Christina Schnopp, Annette F. Jansson, Deniz Ayvaz, Nadejda Shabashova, Liudmyla Chernyshova, Anastasia Bondarenko, Despina Moshous, Benedicte Neven, Chahinez Boubidi, Fatima Ailal, Giuliana Giardino, Stefano Del Giacco, Marie-Elisabeth Bougnoux, Kohsuke Imai, Teppei Okawa, Yoko Mizoguchi, Yusuke Ozaki, Masato Takeuchi, Akira Hayakawa, Birgit Logering, Kristian Reich, Timo Buhl, Kilian Eyerich, Martin Schaller, Peter D. Arkwright, Andrew R. Gennery, Andrew J. Cant, Adilia Warris, Stefanie Henriet, Najla Mekki, Ridha Barbouche, Imen BenMustapha, Christine Bodemer, Michel Polak, EmmanuelGrimprel, Pierre-R ́egis Burgel, Alain Fischer, Olivier Hermine, Marianne Debr ́e, Dilara Kocacyk, Fatima Dhalla, Smita Y. Patel, Leen Moens, Filomeen Haerynck, Melissa Dullaers, Levi Hoste, Ozden Sanal, Sara Sebnem Kilic, Joachim Roesler, Fanny Lanternier, Olivier Lortholary, Claire Fieschi, Joseph A. Church, Chaim Roifman, Araya Yuenyongviwat, Part Peterson, Stéphanie Boisson-Dupuis, Laurent Abel, Beatriz E. Marciano, Mihai G. Netea
المساهمون: Toubiana, Okada, Julie, Hiller, Satoshi, Oleastro, Julia, Gomez, Matia, Becerra, Macarena Lago, Ouachãe chardin, Juan Carlos Aldave, Fouyssac, Marie, Girisha, Fanny, Etzioni, Katta Mohan, Van Montfrans, Amo, Camcioglu, Jori, Kerns, Yildiz, Belohradsky, Leigh Ann, Blanche, Bernd, Bousfiha, Stephane, Rodriguez gallego, Aziz, Meyts, Carlo, Kisand, Isabelle, Reichenbach, Kai, Renner, Janine, Rosenzweig, Ellen D., Grimbacher, Sergio, Van De Veerdonk, Bodo, Traidl hoffmann, Frank L., Picard, Claudia, Marodi, Capucine, Morio, Laszlo, Kobayashi, Tomohiro, Lilic, Masao, Milner, Desa, Holland, Joshua D., Casanova, Steven, Puel, Jean Laurent, Cypowyj, Anne, Sophie, Thumerelle, Caroline, Toulon, Antoine, Bustamante, Jacinta, Tahuil, Natalia, Salhi, Aicha, Boiu, Sorina, Chopra, Charu, Di Giovanni, Daniela, Bezrodnik, Liliana, Jeannetteboutros, Thomas, Caroline, Lacuesta, Gina, Jannier, Sarah, Korganow, Anne-Sophie, Paillard, Catherine, Boutboul, David, Bu ́e, M ́elanie, Marie-Cardine, Aude, Bayart, Sophie, Migaud, Mélanie, Weiss, Laurence, Karmochkine, Marina, Garcia-Martinez, Juan-Miguel, Stephan, Jean-Loui, Bensaid, Philippe, Jeannoel, Guy-Patrick, Witte, Torsten, Baumann, Ulrich, Harrer, Thoma, Navarrete, Carmen, Terance Benjamin, Antony, Firinu, Davide, Pignata, Claudio, Picco, Paolo, Mendoza, David, Oswaldo Lugo Reyes, Saul, Torres Lozano, Carlo, MargaritaOrtega-Cisneros, Cortina, Mariana, Mesdaghi, Mehrnaz, Mohammadnabavi, Español, Teresa, Teresa Martinez- Saavedra, Maia, Rezaei, Nima, Zoghi, Samaneh, Pac, Malgorzata, Barlogis, Vincent, Revon-Rivire, Gabriel, Haimi-Cohen, Yishai, Spiegel, Ronen, Miron, Dan, Bouchaib, Jabir, Blancas-Galicia, Lizbeth, Toth, Beata, Drexel, Barbara, Simon Roherlich, Pierre, Lesens, Olivier, Hoernes, Miriam, Drewe, Elizabeth, Abinum, Mario, Sawalle-Belohradsky, Julie, Kindle, Gerhard, Depner, Mark, Milani, Lili
مصطلحات موضوعية: Adolescent, Adult, Aged, Candidiasis, Chronic mucocutaneou, Child, preschool, Cohort studie, Female, Genetic predisposition to disease, Heterozygote, Human, Infant, Male, Middle aged, Phenotype, STAT1 transcription factor, Young adult, Genetic association studie, Mutation, Biochemistry, Immunology, Hematology, Cell biology
الوصف: Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guérin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/27114460; info:eu-repo/semantics/altIdentifier/wos/WOS:000378337700009; volume:127; issue:25; firstpage:3154; lastpage:3164; numberofpages:11; journal:BLOOD; http://hdl.handle.net/11584/225549Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84977482520; http://www.bloodjournal.org/content/bloodjournal/127/25/3154.full.pdfTest
الإتاحة: https://doi.org/10.1182/blood-2015-11-679902Test
http://hdl.handle.net/11584/225549Test
http://www.bloodjournal.org/content/bloodjournal/127/25/3154.full.pdfTest -
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المؤلفون: Carolyn Henderson, Bernd H. Belohradsky, Amy P. Hsu, Annette Boos, Anne Langenbeck, Beate Hagl, King F. Kwong, Pamela Welch, Julie Sawalle-Belohradsky, Lisa Boris, Ellen D. Renner, Steven M. Holland, Kenneth N. Olivier, Joie Davis, Alexandra F. Freeman, Beatriz E. Marciano
المصدر: Journal of Clinical Immunology. 33:896-902
مصطلحات موضوعية: Adult, Lung Diseases, Male, STAT3 Transcription Factor, medicine.medical_specialty, Adolescent, Immunology, Bronchopleural fistula, Young Adult, Parenchyma, medicine, Humans, Immunology and Allergy, Child, Lung, Retrospective Studies, Wound Healing, Bronchiectasis, business.industry, Medical record, Retrospective cohort study, Middle Aged, medicine.disease, Surgery, medicine.anatomical_structure, Child, Preschool, Mutation, Primary immunodeficiency, Female, business, Complication, Job Syndrome
الوصف: Autosomal dominant hyper-IgE syndrome (AD-HIES) due to heterozygous STAT3 mutation is a primary immunodeficiency characterized by eczema, elevated serum IgE, recurrent infections, and connective tissue and skeletal findings. Healing of pneumonias is often abnormal with formation of pneumatoceles and bronchiectasis. We aimed to explore whether healing after lung surgery is also aberrant. We retrospectively analyzed the medical records of 32 patients with AD-HIES who received lung surgery for the management of pulmonary infections from 1960 to 2011. We collected information including patient demographics, STAT3 mutation status, clinical history, surgical and medical procedures performed, complications, related medical treatments, and outcomes. More than 50 % of lung surgeries had associated complications, with the majority being prolonged bronchopleural fistulae. These fistulae often led to empyemas that necessitated additional interventions including prolonged antibiotics, prolonged thoracostomy tube drainage and re-operations. Lung surgery in AD-HIES patients is associated with high complication rates. STAT3 mutations likely lead to abnormalities in tissue remodelling that are further exacerbated by infection.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf493785d8b3db9e6d003bac99c8995aTest
https://doi.org/10.1007/s10875-013-9890-5Test -
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المؤلفون: Janet Chou, Emily M. Mace, Kathleen E. Sullivan, Michael H. Albert, Linda Monaco-Shawver, Raif S. Geha, Alexandra F. Freeman, Waleed Al-Herz, William Bernal, Pinaki P. Banerjee, Valerie Heinz, Melissa C. Mizesko, Jordan S. Orange, Ellen D. Renner, Troy R. Torgerson, Steven M. Holland, Imelda C. Hanson, Julie Sawalle-Belohradsky, Bernd H. Belohradsky
المصدر: Journal of Allergy and Clinical Immunology. 131:840-848
مصطلحات موضوعية: Adult, Male, Adolescent, Wiskott–Aldrich syndrome, Immunology, Cell, macromolecular substances, Biology, Filamentous actin, Article, Interleukin 21, medicine, Guanine Nucleotide Exchange Factors, Humans, Immunology and Allergy, Child, Lymphokine-activated killer cell, Immunologic Deficiency Syndromes, Infant, medicine.disease, Actins, Killer Cells, Natural, medicine.anatomical_structure, Lytic cycle, Child, Preschool, Female, Dock8, K562 Cells, DOCK8 Deficiency
الوصف: Background Dedicator of cytokinesis 8 (DOCK8) mutations are responsible for a rare primary combined immunodeficiency syndrome associated with severe cutaneous viral infections, increased IgE levels, autoimmunity, and malignancy. Natural killer (NK) cells are essential for tumor surveillance and defense against virally infected cells. NK cell function relies on Wiskott-Aldrich syndrome protein for filamentous actin (F-actin) accumulation at the lytic NK cell immunologic synapse. DOCK8 activates cell division cycle 42, which, together with Wiskott-Aldrich syndrome protein, coordinates F-actin reorganization. Although abnormalities in T- and B-cell function have been described in DOCK8-deficient patients, the role of NK cells in this disease is unclear. Objectives We sought to understand the role of DOCK8 in NK cell function to determine whether NK cell abnormalities explain the pathogenesis of the clinical syndrome of DOCK8 deficiency. Methods A cohort of DOCK8-deficient patients was assembled, and patients' NK cells, as well as NK cell lines with stably reduced DOCK8 expression, were studied. NK cell cytotoxicity, F-actin content, and lytic immunologic synapse formation were measured. Results DOCK8-deficient patients' NK cells and DOCK8 knockdown cell lines all had decreased NK cell cytotoxicity, which could not be restored after IL-2 stimulation. Importantly, DOCK8 deficiency impaired F-actin accumulation at the lytic immunologic synapse without affecting overall NK cell F-actin content. Conclusions DOCK8 deficiency results in severely impaired NK cell function because of an inability to form a mature lytic immunologic synapse through targeted synaptic F-actin accumulation. This defect might underlie and explain important attributes of the DOCK8 deficiency clinical syndrome, including the unusual susceptibility to viral infection and malignancy.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::804c29dc74e3a92d970e454a354ea309Test
https://doi.org/10.1016/j.jaci.2012.12.1568Test -
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المؤلفون: Michael H. Albert, Georg Mann, Susanne Matthes-Martin, Alexandra Rümmele-Waibel, Ellen D. Renner, René Geyeregger, Bernd Ausserer, Christina Peters, Julie Sawalle-Belohradsky, Bernd H. Belohradsky, Anita Lawitschka, Cäcilia Karitnig-Weiß, Karoly Lakatos, Heidrun Boztug, Ernst Horcher
المصدر: Pediatric Hematology and Oncology. 29:585-594
مصطلحات موضوعية: Transplantation Conditioning, medicine.medical_treatment, DNA Mutational Analysis, Hematopoietic stem cell transplantation, medicine, Guanine Nucleotide Exchange Factors, Humans, Transplantation, Homologous, Eosinophilia, Pneumonitis, business.industry, Hematopoietic Stem Cell Transplantation, Immunologic Deficiency Syndromes, Hematology, medicine.disease, Pedigree, Transplantation, Regimen, surgical procedures, operative, Oncology, Child, Preschool, Mutation, Pediatrics, Perinatology and Child Health, Immunology, Eczematous dermatitis, Female, medicine.symptom, business, DOCK8 Deficiency, Aspergilloma
الوصف: Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db6fae439964f186d7f93b4b8c1a66c2Test
https://doi.org/10.3109/08880018.2012.714844Test -
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المؤلفون: Monika Senn-Rauh, Cäcilia Karitnig-Weiss, Annette Boos, Josef Frank, Annette Jansson, V. Wahn, Ellen D. Renner, Michael H. Albert, Julie Sawalle-Belohradsky, Manfred Hönig, Horst von Bernuth, Beate Hagl, Valerie Heinz, Thomas Magg, Anne Schlesinger, Andreas Wollenberg, C. Pache, Benedikt D. Spielberger, Bernd H. Belohradsky, Klaus Schwarz, Tim Niehues, Gregor Dückers
المصدر: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 27(2)
مصطلحات موضوعية: 0301 basic medicine, Male, STAT3 Transcription Factor, T-Lymphocytes, Immunology, Immunoglobulin E, medicine.disease_cause, Lymphocyte Activation, Dermatitis, Atopic, Diagnosis, Differential, 03 medical and health sciences, medicine, Immunology and Allergy, Guanine Nucleotide Exchange Factors, Humans, Cells, Cultured, B-Lymphocytes, biology, business.industry, Infant, Atopic dermatitis, Immune dysregulation, medicine.disease, 030104 developmental biology, Job Syndrome, Child, Preschool, Pediatrics, Perinatology and Child Health, Mutation, biology.protein, Primary immunodeficiency, Cytokines, Female, Dock8, Differential diagnosis, Cell activation, business, Immunologic Memory
الوصف: BackgroundHyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by elevated serum IgE, eczema, and recurrent infections. Despite the availability of confirmatory molecular diagnosis of several distinct HIES entities, the differentiation of HIES particularly from severe forms of atopic dermatitis remains a challenge. The two most common forms of HIES are caused by mutations in the genes STAT3 and DOCK8. MethodsHere, we assess the clinical and immunologic phenotype of DOCK8- and STAT3-HIES patients including the cell activation, proliferation, and cytokine release after stimulation. ResultsExisting HIES scoring systems are helpful to identify HIES patients. However, those scores may fail in infants and young children due to the age-related lack of clinical symptoms. Furthermore, our long-term observations showed a striking variation of laboratory results over time in the individual patient. Reduced memory B-cell counts in concert with low specific antibody production are the most consistent findings likely contributing to the high susceptibility to bacterial and fungal infection. In DOCK8-HIES, T-cell lymphopenia and low IFN-gamma secretion after stimulation were common, likely promoting viral infections. In contrast to STAT3-HIES, DOCK8-HIES patients showed more severe inflammation with regard to allergic manifestations, elevated activation markers (HLA-DR, CD69, CD86, and CD154), and significantly increased inflammatory cytokines (IL1-beta, IL4, IL6, and IFN-gamma). ConclusionDifferentiating HIES from other diseases such as atopic dermatitis early in life is essential for patients because treatment modalities differ. To expedite the diagnosis process, we propose here a diagnostic workflow.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::955d1201cb8535d13d9adc51f3cf1e05Test
https://pubmed.ncbi.nlm.nih.gov/26592211Test -
9
المؤلفون: Bernd H. Belohradsky, Miriam Hoernes, Sophie Cypowyj, Janine Reichenbach, Saleh Al-Muhsen, Magali Audry, Joachim Roesler, Amos Etzioni, Francisco Espinosa Rosales, Matías Oleastro, Luyan Liu, Tatiana Kochetkov, Viktor P. Chernyshov, Olivier Lortholary, Cécile Masson, Julie Toubiana, Stéphane Blanche, Caroline Thumerelle, Reinhard Seger, Dan Engelhard, Beáta Tóth, Yuval Itan, Lizbeth Blancas-Galicia, Patrick Nitschke, Gizi Wildbaum, Ludmyla Chernyshova, Avinash Abhyankar, Jérome Flatot, Ellen D. Renner, Ileana Maria Madrigal Beas, Xiao-Fei Kong, Maya Chrabieh, Antoine Toulon, Capucine Picard, Masao Kobayashi, László Maródi, J. Hiller, Alexandra Y. Kreins, Christine Bodemer, Julie Sawalle-Belohradsky, Alexandre Bolze, Claudia Traidl-Hoffmann, Stéphanie Boisson-Dupuis, Jean-Laurent Casanova, Anastasia Bondarenko, Alain Fischer, Emmanuelle Jouanguy, Laurent Abel, Theresia Kusuma, Nathan Karin, Rosa María Cortés Grimaldo, Pierre-Régis Burgel, Alessandro Borghesi, Annette Jansson, Anne Puel, Mélanie Bué, Jacinta Bustamante, Kilian Eyerich, Mélanie Migaud, Carlos Torres Lozano, Stefanie Eyerich, Barbara Drexel, Sara Sebnem Kilic, Klaus Magdorf, Satoshi Okada, Vera Gulácsy
المساهمون: Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı., Kılıç, Sara Şebnem, University of Zurich, Puel, A
المصدر: The Journal of Experimental Medicine
J. Exp. Med. 208, 1635-1648 (2011)مصطلحات موضوعية: Male, Models, Molecular, medicine.medical_treatment, T-Lymphocytes, Job Syndrome, Mucocutaneous Candidiasis, Mutation, Fluorescent Antibody Technique, Interleukin 6, Electrophoretic Mobility Shift Assay, Receptor, Interferon alpha-beta, Gene, Interleukin 22, 0302 clinical medicine, Hyper-ige syndrome, Interleukin 17, Gain of function mutation, T lymphocyte, Immunology and Allergy, Disease, Chronic mucocutaneous candidiasis, Sequencing-based discovery, hyper-ige syndrome, sequencing-based discovery, cd4(+) t-cells, th17 cells, inborn-errors, ifn-gamma, th17-associated cytokines, deficiency, disease, il-27, Phosphorylation, Child, Dominance (genetics), Priority journal, Allele, 0303 health sciences, Heterozygosity, Candidiasis, Chronic Mucocutaneous, Interleukin-17, Flow Cytometry, 3. Good health, Pedigree, Cytokine, STAT1 Transcription Factor, 2723 Immunology and Allergy, Deficiency, Mucocutaneous candidiasis, Female, Cd4(+) t-cells, Inborn-errors, Human, Il-27, Interleukin 17F, Clinical article, Immunology, Immunoblotting, Molecular Sequence Data, Research & experimental medicine, 610 Medicine & health, Enzyme-Linked Immunosorbent Assay, Biology, Chronic disease, Article, 03 medical and health sciences, Interferon-gamma, Germline mutation, Immunity, STAT1 protein, Stat 1 gene, medicine, Autosomal dominant disorder, Humans, Th17-associated cytokines, ddc:610, Th17 cells, Medicine, research & experimental, Germ-Line Mutation, 030304 developmental biology, 2403 Immunology, Base Sequence, Interleukins, Infant, Heterozygote advantage, Sequence Analysis, DNA, medicine.disease, Interleukin 21, 10036 Medical Clinic, Interferons, Ifn-gamma, Sequence Alignment, 030215 immunology
الوصف: Whole-exome sequencing reveals activating STAT1 mutations in some patients with autosomal dominant chronic mucocutaneous candidiasis disease.
Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.وصف الملف: application/pdf; LiuL,_2011.pdf - application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f22afce4bf3f7b792989039cf399f52Test
http://europepmc.org/articles/PMC3149226Test -
10
المؤلفون: Ellen D. Renner, Philip Bufler, Michael H. Albert, Andreas Wollenberg, Valerie Heinz, Oliver Ehrt, Beate Hagl, Jens Neumann, Martin Ries, Julie Sawalle-Belohradsky, Cihan Papan
المصدر: Journal of Allergy and Clinical Immunology. 133:1456-1458
مصطلحات موضوعية: business.industry, Immunology, Immunology and Allergy, Medicine, business, Virology, Dedicator of cytokinesis 8
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::263cc4a8304509fd607e9739695b2f4aTest
https://doi.org/10.1016/j.jaci.2014.02.008Test