Research Topics
Genomes and Genes
| Daniel L KastnerSummaryAffiliation: National Institutes of Health Country: USA Publications
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Detail Information
Publications
Autoinflammatory disease reloaded: a clinical perspectiveDaniel L Kastner
Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Cell 140:784-90. 2010..Recent advances offer new opportunities for therapeutic intervention and suggest that the definition of what constitutes an autoinflammatory disease should be reassessed...- The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragmentJae Jin Chae
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892 1820, USA
Blood 112:1794-803. 2008..Our data support a new pyrin/caspase-1 pathway for NF-kappaB activation... - Familial Mediterranean fever with a single MEFV mutation: where is the second hit?Matthew G Booty
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892 1820, USA
Arthritis Rheum 60:1851-61. 2009..The purpose of this study was to perform an extensive search for a second MEFV mutation in 46 patients diagnosed clinically as having FMF and carrying only 1 high-penetrance FMF mutation... 
De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseasesIvona Aksentijevich
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA
Arthritis Rheum 46:3340-8. 2002....- Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1β activation and severe autoinflammation in miceJae Jin Chae
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 34:755-68. 2011..Thus, our data provide evidence for an ASC-dependent NLRP3-independent inflammasome in which gain-of-function pyrin mutations cause autoinflammatory disease... - Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS)Ariel C Bulua
Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutesof Health, Bethesda, MD 20892, USA
J Exp Med 208:519-33. 2011..These findings suggest that mitochondrial ROS may be a novel therapeutic target for TRAPS and other inflammatory diseases... - Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathwayNitza G Shoham
Genetics and Genomics Branch and Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 100:13501-6. 2003.... 
The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMPGeun Shik Lee
Inflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 492:123-7. 2012..Taken together, these findings indicate that Ca(2+) and cAMP are two key molecular regulators of the NLRP3 inflammasome that have critical roles in the molecular pathogenesis of CAPS...- The chromosome 7q region association with rheumatoid arthritis in females in a British population is not replicated in a North American case-control seriesBenjamin D Korman
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892 1849, USA
Arthritis Rheum 60:47-52. 2009..We sought to replicate this finding and to better characterize susceptibility alleles in the region in a North American population... - The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta productionJae Jin Chae
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 103:9982-7. 2006..Our data support a direct, ASC-independent effect of pyrin on IL-1beta activation and suggest heightened IL-1 responsiveness as one factor selecting for pyrin mutations... - Advances in the understanding of familial Mediterranean fever and possibilities for targeted therapyJae J Chae
Laboratory of Clinical Investigation, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, Genetics and Genomics Branch, Bethesda, MD 20892 1849, USA
Br J Haematol 146:467-78. 2009..In addition to the regulatory role of pyrin for caspase-1, the cleavage of pyrin provides an important clue not only in understanding the molecular pathogenesis of FMF but also in developing new therapeutic targets for FMF... - A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiencyQing Zhou
Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD 20892, USA
Am J Hum Genet 91:713-20. 2012..Our results highlight the utility of exome-sequencing technology in finding causal mutations in nuclear families with dominantly inherited traits otherwise intractable by linkage analysis... - Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne)Andrew P Demidowich
National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
Arthritis Rheum 64:2022-7. 2012..To describe the genotypes, phenotypes, immunophenotypes, and treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), a rare autoinflammatory disease, in 5 patients... - Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*)Seth L Masters
The National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Annu Rev Immunol 27:621-68. 2009..A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside... - STAT4: genetics, mechanisms, and implications for autoimmunityBenjamin D Korman
National Institute of Arthritis, Musculoskeletal, and Skin Diseases, 9 Memorial Drive, NIH Building 9, Room 1W108, Bethesda, MD 20892, USA
Curr Allergy Asthma Rep 8:398-403. 2008..In concert with the identification of other disease-associated loci, elucidating how the variant form of STAT4 modulates immune function should lead to an improved understanding of the pathophysiology of autoimmunity... - Recent advances in the molecular pathogenesis of hereditary recurrent feversSeth L Masters
The National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda 20892, Maryland, USA
Curr Opin Allergy Clin Immunol 6:428-33. 2006.... - Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndromeAnna Simon
Inflammatory Biology Section, Laboratory of Clinical Investigation and Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 107:9801-6. 2010.... - Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation studyAriel C Bulua
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA
Arthritis Rheum 64:908-13. 2012..To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS)... - The hereditary autoinflammatory syndromesPuja Chitkara
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Center Drive, Bethesda, MD, USA
Pediatr Infect Dis J 26:353-4. 2007 - A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndromeRaphaela Goldbach-Mansky
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA
Arthritis Rheum 58:2432-42. 2008..This pilot study was conducted to assess the safety and efficacy of rilonacept (IL-1 Trap), a long-acting IL-1 receptor fusion protein, in patients with FCAS... - An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonistIvona Aksentijevich
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
N Engl J Med 360:2426-37. 2009..We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone... - Lighting the fires within: the cell biology of autoinflammatory diseasesHeiyoung Park
Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS, National Institutes of Health NIH, Bethesda, Maryland, USA
Nat Rev Immunol 12:570-80. 2012.... - Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunitySusannah D Brydges
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 30:875-87. 2009..These data suggest that CAPS are true inflammasome-mediated diseases and provide insight for more common inflammatory disorders... - Autoinflammation: the prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnessesRaphaela Goldbach-Mansky
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Allergy Clin Immunol 124:1141-9; quiz 1150-1. 2009.... - Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndromeKazuki Takada
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Arthritis Rheum 48:2645-51. 2003..CONCLUSION: Our favorable experience with etanercept for the treatment of HIDS suggests that further investigation of this therapy is warranted... - Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1Yohei Kirino
1 Inflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA 2 Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan 3
Nat Genet 45:202-7. 2013.... - Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletionsMichael J Ombrello
Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
N Engl J Med 366:330-8. 2012..Mendelian analysis of disorders of immune regulation can provide insight into molecular pathways associated with host defense and immune tolerance... - Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosisJae Jin Chae
Inflammatory Biology Section, Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA
Mol Cell 11:591-604. 2003..These data support a critical role for pyrin in the innate immune response, possibly by acting on ASC, and suggest a biologic basis for the selection of hypomorphic pyrin variants in man... - Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's diseaseElaine F Remmers
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA
Nat Genet 42:698-702. 2010..34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production... - Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibitionRaphaela Goldbach-Mansky
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
N Engl J Med 355:581-92. 2006..Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation... - The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin modelIvona Aksentijevich
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892 1820, USA
Arthritis Rheum 56:1273-85. 2007..This study was undertaken to investigate the structural effect of disease-causing mutations on cryopyrin, in order to gain better understanding of the impact of disease-associated mutations on protein function... - Monocytic fasciitis: a newly recognized clinical feature of tumor necrosis factor receptor dysfunctionKeith M Hull
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA
Arthritis Rheum 46:2189-94. 2002..These results suggest that the myalgia experienced by individuals with TRAPS is due to a monocytic fasciitis and not to myositis... - The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorderKeith M Hull
Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Medicine (Baltimore) 81:349-68. 2002..Our laboratories are currently undertaking both clinical and basic research studies to define the role of these mutations in more common inflammatory diseases... - Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS)Adrian A Lobito
Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda MD 20892, USA
Blood 108:1320-7. 2006..In contrast, the R92Q variant of TNFR1 behaved like the wild-type receptor in all of these assays. The inflammatory phenotype of TRAPS may be due to consequences of mutant TNFR1 protein misfolding and ER retention... - Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockadeSilvia Stojanov
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 108:7148-53. 2011..IL-1 inhibition may thus be beneficial for treatment of PFAPA attacks, with IP-10/CXCL10 serving as a potential biomarker... - Familial autoinflammatory diseases: genetics, pathogenesis and treatmentSilvia Stojanov
Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Curr Opin Rheumatol 17:586-99. 2005..This review elucidates how recent advances have impacted diagnosis, pathogenesis, and treatment... - Challenges and opportunities for systemic amyloidosis research. Summary of an advisory workshop sponsored by the NIH Office of Rare Diseases, Bethesda, Maryland, June 20, 2006Daniel G Wright
The Hematology Research Program, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA
Amyloid 14:103-12. 2007 - STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosusElaine F Remmers
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA
N Engl J Med 357:977-86. 2007..Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q... - The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestationsKeith M Hull
Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Curr Opin Rheumatol 15:61-9. 2003..Lastly, the authors discuss the broadening genetic and clinical spectrum of TRAPS, an autoinflammatory syndrome resulting from mutations in the 55-kDa receptor for tumor necrosis factor... - Human transthyretin intronic open reading frames are not independently expressed in vivo or part of functional transcriptsMiguel Luz Soares
Arthritis and Rheumatism Branch, Genetics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bldg 10, Rm 9N216, 9000 Rockville Pike, Bethesda, MD 20892, USA
Biochim Biophys Acta 1626:65-74. 2003..Neither ORF is productively expressed as part of a larger transcript, or as an independent polypeptide... - Characterization and analysis of the proximal Janus kinase 3 promoterMartin Aringer
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 170:6057-64. 2003..Thus, transcription factors that bind these sites, especially Ets family members, are likely to be important regulators of Jak3 expression...