Genomes and Genes
Hal M Hoffman
Affiliation: University of California
- Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studiesHal M Hoffman
Division of Rheumatology and Allergy Immunology, University of California at San Diego, La Jolla, CA 92093 0635, USA
Arthritis Rheum 58:2443-52. 2008....
- Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonistHal M Hoffman
Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, La Jolla, CA 92093 0635, USA
Lancet 364:1779-85. 2004..The genetic basis of this disease has been elucidated. Cryopyrin, the protein that is altered in FCAS, is one of the adaptor proteins that activate caspase 1, resulting in release of interleukin 1...
- An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injuryAlana A Shigeoka
Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA
J Immunol 185:6277-85. 2010..We conclude that Nlrp3 contributes to renal IRI by a direct effect on renal tubular epithelium and that this effect is independent of inflammasome-induced proinflammatory cytokine production...
- Monocytes from familial cold autoinflammatory syndrome patients are activated by mild hypothermiaSanna Rosengren
Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, La Jolla, CA 92093 0635, USA
J Allergy Clin Immunol 119:991-6. 2007..CIAS1, the gene that codes for cryopyrin, is mutated in FCAS. Treatment with anakinra (IL-1 receptor antagonist) prevents symptoms, indicating a crucial role for IL-1 in this disease...
- NLRP3 inflammasome activation is required for fibrosis development in NAFLDAlexander Wree
Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, MC 0715, La Jolla, CA, 92037 0715, USA
J Mol Med (Berl) 92:1069-82. 2014..Patients with severe NAFLD exhibit increased levels of NLRP3 inflammasome components and levels of pro-IL1β mRNA correlate with the expression of COL1A1...
- Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension studyHal M Hoffman
University of California San Diego, La Jolla, USA
Clin Ther 34:2091-103. 2012..The interleukin-1 inhibitor rilonacept has been shown to be well-tolerated and effective in preventing CAPS symptoms in 2 pivotal studies...
- Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse modelsMatthew D McGeough
Department of Pediatrics, University of California at San Diego, La Jolla, CA 92093, USA
J Immunol 189:2707-11. 2012..Taken together, our results indicate that IL-6 is a reliable marker of inflammation, with no direct role in inflammasome-mediated disease...
- Recurrent febrile syndromes: what a rheumatologist needs to knowHal M Hoffman
University of California at San Diego, La Jolla, CA 92093, USA
Nat Rev Rheumatol 5:249-56. 2009..NSAIDs, colchicine and corticosteroids have roles in the treatment of some of these disorders, but biologic drugs that target interleukin-1beta are emerging as consistently effective therapies...
- Mutations of complement factor I and potential mechanisms of neuroinflammation in acute hemorrhagic leukoencephalitisLori Broderick
Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, 9500 Gilman Dr MC 0635, La Jolla, CA 92093, USA
J Clin Immunol 33:162-71. 2013....
- ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6Marina Miller
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 109:16648-53. 2012..These studies provide evidence of the inducible nature of ORMDL3 ER expression in particular in bronchial epithelial cells and suggest an ER UPR pathway through which ORMDL3 may be linked to asthma...
- MDP-induced interleukin-1beta processing requires Nod2 and CIAS1/NALP3Qilin Pan
Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
J Leukoc Biol 82:177-83. 2007..Together, our data provide a new understanding of this important pathway of IL-1beta production and allow for further studies of the role of these proteins within the broader context of inflammatory disease...
- Identification of EpCAM as the gene for congenital tufting enteropathyMamata Sivagnanam
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, La Jolla, California, USA
Gastroenterology 135:429-37. 2008..The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE...
- Successful treatment of renal amyloidosis due to familial cold autoinflammatory syndrome using an interleukin 1 receptor antagonistBrian D Thornton
Division of Nephrology, University of California Davis Medical Center, La Jolla, CA, USA
Am J Kidney Dis 49:477-81. 2007..Use of specific anticytokine therapy may be a new paradigm in the treatment of patients with renal amyloidosis caused by systemic inflammatory diseases...
- Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activityHal M Hoffman
University of California at San Diego, La Jolla, CA 92093 0635, USA
Curr Med Res Opin 24:2531-43. 2008..Development of an instrument for characterization of symptom patterns and severity in patients with cryopyrin-associated periodic syndromes (CAPS)...
- Hereditary immunologic disorders caused by pyrin and cryopyrinHal M Hoffman
Division of Rheumatology, Allergy, and Immunology, University of California at San Diego Medical School, 9500 Gilman Drive, La Jolla, CA 92093 0635, USA
Curr Allergy Asthma Rep 7:323-30. 2007..These advances have also resulted in direct improvement in diagnosis and therapy for autoinflammatory disorders such as the cryopyrinopathies and familial Mediterranean fever and have implications for more common inflammatory diseases...
- Recurrent fever syndromes in patients after recovery from Kawasaki syndromeLori Broderick
Department of Pediatrics, University of California San Diego and Rady Children s Hospital, San Diego, California, USA
Pediatrics 127:e489-93. 2011..We propose that these 2 syndromes exist within a family of febrile disorders related to innate immune dysregulation...
- NLRP3 mediates osteolysis through inflammation-dependent and -independent mechanismsChao Qu
Division of Bone and Mineral Diseases and Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri, USA and Division of Allergy, Immunology, and Rheumatology, University of California, San Diego, La Jolla, California, USA
FASEB J 29:1269-79. 2015..Thus, NLRP3 inflammasome activation is not restricted to the production of proinflammatory mediators but also leads to cytokine-autonomous responses...
- Familial atypical cold urticaria: description of a new hereditary diseaseChhavi Gandhi
Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla, CA, USA
J Allergy Clin Immunol 124:1245-50. 2009..We describe 3 unrelated families (A, B, and C) with lifelong atypical cold urticaria distinguished from ACU and familial cold autoinflammatory syndrome...
- Inflammasome and IL-1beta-mediated disordersHal M Hoffman
Division of Allergy and Immunology, University of California at San Diego and Rady Children s Hospital of San Diego, La Jolla, CA 92093, USA
Curr Allergy Asthma Rep 10:229-35. 2010..However, many other diseases are likely to be mediated by the inflammasome and interleukin-1beta, providing additional targets in the future...
- Therapy of autoinflammatory syndromesHal M Hoffman
Department of Pediatrics and Medicine, Division of Allergy, Immunology, and Rheumatology, University of California at San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093 0635, USA
J Allergy Clin Immunol 124:1129-38; quiz 1139-40. 2009..This article reviews the general approach to the therapy of autoinflammatory diseases, focusing on current approved therapies and novel approaches that might be used in the future...
- Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS)Hal M Hoffman
University of California at San Diego, Division of Rheumatology and Allergy Immunology, Mail Code 0635, 9500 Gilman Drive, La Jolla, CA 92093 0635, USA
Expert Opin Biol Ther 9:519-31. 2009..Until recently, there was no effective treatment for CAPS, but identification of the genetic basis of CAPS highlighted the pathogenic role of IL-1beta...
- Definition of IFN-γ-related pathways critical for chemically-induced systemic autoimmunityK Michael Pollard
Department of Molecular and Experimental Medicine, MEM125, Scripps Research Institute, La Jolla, CA 92037, USA
J Autoimmun 39:323-31. 2012..These findings have implications for the therapeutic targeting of IFN-γ pathways in systemic autoimmunity...
- Interleukin 1 receptor signaling regulates DUBA expression and facilitates Toll-like receptor 9-driven antiinflammatory cytokine productionJose M Gonzalez-Navajas
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
J Exp Med 207:2799-807. 2010..Our data identifies a new molecular pathway by which IL-1 signaling attenuates TLR9-mediated proinflammatory responses...
- Structural, expression, and evolutionary analysis of mouse CIAS1Justin P Anderson
Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
Gene 338:25-34. 2004..We also detected significant expression in mouse eye and skin tissue, which is consistent with symptoms observed in human Cryopyrin-associated diseases...
- NF-κB Restricts Inflammasome Activation via Elimination of Damaged MitochondriaZhenyu Zhong
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Department of Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Cell 164:896-910. 2016....
- The role of the inflammasome in patients with autoinflammatory diseasesHal M Hoffman
Division of Pediatric Allergy, Immunology, and Rheumatology, University of California at San Diego, and Rady Children s Hospital of San Diego, La Jolla, Calif Electronic address
J Allergy Clin Immunol 138:3-14. 2016..This review will focus on understanding the molecular basis of inflammasomes, recognizing the distinguishing features of the classic autoinflammatory disorders, and appreciating the treatment modalities available. ..
- A group A Streptococcus ADP-ribosyltransferase toxin stimulates a protective interleukin 1β-dependent macrophage immune responseAnn E Lin
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA
MBio 6:e00133. 2015..Thus, SpyA triggers caspase-1-dependent inflammatory cell death in macrophages, revealing a toxin-triggered IL-1β-dependent innate immune response pathway critical in defense against invasive bacterial infection...
- The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis mediaArwa Kurabi
School of Medicine, Department of Surgery, Division of Otolaryngology, University of California San Diego, La Jolla, CA, USA
Innate Immun 21:203-14. 2015..These data demonstrate an important role for the inflammasome and cytokine processing in the course and resolution of OM. ..
- From NAFLD to NASH to cirrhosis-new insights into disease mechanismsAlexander Wree
Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037 0715, USA
Nat Rev Gastroenterol Hepatol 10:627-36. 2013..These studies bring new insight into this complex disorder and have led to the development of novel therapeutic and diagnostic strategies that might enable a personalized approach in the management of this disease. ..
- Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353PHal M Hoffman
Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0635, USA
Hum Genet 112:209-16. 2003..We also report a comprehensive list of intragenic single nucleotide polymorphisms. The data provided here will assist others researching the 1q44 region and will aid clinicians in the diagnosis of FCAS...
- Autoinflammation: translating mechanism to therapyTaylor A Doherty
Division of Allergy, Immunology, and Rheumatology, University of California at San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093 0635, USA
J Leukoc Biol 90:37-47. 2011..Here, we review current treatment strategies of autoinflammatory diseases with a focus on IL-1 antagonism...
- Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activityGeorge Y Liu
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
J Exp Med 202:209-15. 2005..Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy...
- The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathyRalph Knoll
Institute of Molecular Medicine, Department of Medicine, University of California at San Diego, La Jolla 92093, USA
Cell 111:943-55. 2002..We propose that a Z disc MLP/T-cap complex is a key component of the in vivo cardiomyocyte stretch sensor machinery, and that defects in the complex can lead to human DCM and associated heart failure...
- 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...
- A large kindred with familial cold autoinflammatory syndromeReid F Johnstone
Allergy Immunology Section, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia, USA
Ann Allergy Asthma Immunol 90:233-7. 2003..Recently, mutations responsible for FCAS were identified in a novel gene (CIAS1), making it possible to confirm the diagnosis in most patients...
- The spectrum of acquired and familial cold-induced urticaria/urticaria-like syndromesAlan A Wanderer
University of Colorado Health Sciences Center, Denver, USA
Immunol Allergy Clin North Am 24:259-86, vii. 2004..FCAS has become an important investigative syndrome, as it represents a reproducible in vivo model of chronic inflammation...
- Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASCStephen B Willingham
Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Cell Host Microbe 2:147-59. 2007..While similar proteins mediate pathogen-induced cell death in plants, this report identifies cryopyrin as an important host regulator of programmed pathogen-induced necrosis in animals, a process we term pyronecrosis...
- CATERPILLERs, pyrin and hereditary immunological disordersJenny P Y Ting
Department of Microbiology Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA
Nat Rev Immunol 6:183-95. 2006..Most importantly, they are genetically linked to several human immunological disorders...
- A severe case of chronic infantile neurologic, cutaneous, articular syndrome treated with biologic agentsTomoyo Matsubara
Department of Pediatrics, Yamaguchi University School of Medicine, 1 1 1 Minamikogushi, Ube, Yamaguchi 755 8505, Japan
Arthritis Rheum 54:2314-20. 2006..Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder...
- Anakinra prevents symptoms of familial cold autoinflammatory syndrome and Raynaud's diseaseSamy K Metyas
Division of Rheumatology, University of Southern California, Los Angeles, California 90033, USA
J Rheumatol 33:2085-7. 2006..Our report supports increasing evidence that anakinra plays an important role in the treatment of select chronic inflammatory diseases...
- Response to IL-1-receptor antagonist in a child with familial cold autoinflammatory syndromeTurlough Bolger
Department of Dermatology, Our Lady s Children s Hospital, Crumlin, Dublin, Ireland
Pediatr Dermatol 24:85-9. 2007....
- IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patientsJeffrey H Stack
Vertex Pharmaceuticals, San Diego, CA 92121, USA
J Immunol 175:2630-4. 2005..These results further link mutations in cryopyrin with abnormal caspase-1 activation, and support the clinical testing of caspase-1 inhibitors such as VX-765 in autoinflammatory disorders...
- Genomic-based therapy: targeting interleukin-1 for autoinflammatory diseasesHal M Hoffman
Arthritis Rheum 50:345-9. 2004
- The infevers autoinflammatory mutation online registry: update with new genes and functionsFlorian Milhavet
Institut de Genetique Humaine, CNRS UPR1142, Montpellier, France
Hum Mutat 29:803-8. 2008....