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Blau Syndrome (blau + syndrome)
Selected AbstractsGranulomatous rosacea and Crohn's disease in a patient homozygous for the Crohn-associated NOD2/CARD15 polymorphism R702WEXPERIMENTAL DERMATOLOGY, Issue 12 2008M. A. M. Van Steensel Abstract:, NOD2/CARD15 belongs to the N-terminal caspase recruitment domain family of proteins involved in regulating NF-kB activation in response to inflammatory stimuli transduced through Toll-like receptors. Mutations and polymorphisms in the NOD2/CARD15 gene reduce antibacterial responses and are associated with granulomatous inflammatory conditions such as Blau syndrome and early-onset sarcoidosis. The polymorphism R702W (arginine to tryptophan) is strongly associated with susceptibility to Crohn's disease in Caucasian populations. Skin abnormalities (other than cutaneous manifestations of Crohn's disease) have not been previously associated with R702W. We report on a female patient homozygous for R702W who developed granulomatous rosacea at the age of 12 years old. From the occurrence in the context of Crohn associated with R702W, we speculate that granulomatous rosacea may be an entity distinct from other forms of rosacea, which are associated with increased production of antibacterial proteins such as cathelicidin. [source] Autoinflammatory syndromes with a dermatological perspectiveTHE JOURNAL OF DERMATOLOGY, Issue 9 2007Nobuo KANAZAWA ABSTRACT The term autoinflammatory syndromes describes a distinct group of systemic inflammatory diseases apparently different from infectious, autoimmune, allergic and immunodeficient ones. Originally, it was almost synonymous with clinically defined hereditary periodic fever syndromes, including familial Mediterranean fever, hyper immunoglobulin D syndrome with periodic fever and tumor necrosis factor receptor-associated periodic syndrome. Similar but distinct periodic fever syndromes accompanied by urticarial rash, familial cold autoinflammatory syndrome, Muckle,Wells syndrome and chronic infantile neurological cutaneous articular syndrome, have all been reportedly associated with CIAS1 mutations and are collectively called cryopyrin-associated periodic syndromes. Consequently, the concept of autoinflammatory syndromes has been spread to contain other systemic inflammatory diseases: rare hereditary diseases with or without periodic fevers, such as pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome, Blau syndrome and chronic recurrent multifocal osteomyelitis, and the more common collagen disease-like diseases, such as Behcet's disease, Crohn's disease, sarcoidosis and psoriatic arthritis. These diseases are all caused by or associated with mutations of genes regulating innate immunity and have common clinical features accompanied with activation of neutrophils and/or monocytes/macrophages. In this review, major autoinflammatory syndromes are summarized and the pathophysiology of related skin disorders is discussed in association with dysregulated innate immune signaling. [source] Nucleotide-binding oligomerization domain 2 and Toll-like receptor 2 function independently in a murine model of arthritis triggered by intraarticular peptidoglycanARTHRITIS & RHEUMATISM, Issue 4 2010Holly L. Rosenzweig Objective Blau syndrome is an autoinflammatory disease resulting from mutations in the NOD2 gene, wherein granulomatous arthritis, uveitis, and dermatitis develop. The mechanisms by which aberrant NOD2 causes joint inflammation are poorly understood. Indeed, very few studies have addressed the function of nucleotide-binding oligomerization domain 2 (NOD-2) in the joint. This study was undertaken to investigate NOD-2 function in an experimental model of arthritis and to explore the potential interplay between Toll-like receptor 2 (TLR-2) and NOD-2 in joint inflammation. Methods Mice deficient in TLR-2, myeloid differentiation factor 88 (MyD88), or NOD-2 and their wild-type controls were given an intraarticular injection of muramyl dipeptide (MDP), peptidoglycan (PG; a metabolite of which is MDP), or palmitoyl-3-cysteine-serine-lysine-4 (Pam3CSK4), a synthetic TLR-2 agonist. Joint inflammation was assessed by near-infrared fluorescence imaging and histologic analysis. Results Locally administered PG resulted in joint inflammation, which was markedly reduced in mice deficient in either TLR-2 or the TLR signaling mediator MyD88. In addition to TLR-2 signaling events, NOD-2 mediated joint inflammation, as evidenced by the fact that mice deficient in NOD-2 showed significantly reduced PG-induced arthritis. TLR-2 or MyD88 deficiency did not influence arthritis induced by the specific NOD-2 agonist MDP. In addition, NOD-2 deficiency did not alter the TLR-2,dependent joint inflammation elicited by the synthetic TLR-2 agonist Pam3CSK4. Conclusion Whereas NOD-2 and TLR-2 are both critical for the development of PG-induced arthritis, they appear to elicit inflammation independently of each other. Our findings indicate that NOD-2 plays an inflammatory role in arthritis. [source] Interleukin-1, suppression in Blau syndrome: Comment on the article by Martin et alARTHRITIS & RHEUMATISM, Issue 8 2009Junya Masumoto MD No abstract is available for this article. [source] The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activityARTHRITIS & RHEUMATISM, Issue 2 2009Tammy M. Martin Objective Blau syndrome is a rare, autosomal-dominant, autoinflammatory disorder characterized by granulomatous arthritis, uveitis, and dermatitis. Genetics studies have shown that the disease is caused by single nonsynonymous substitutions in NOD-2, a member of the NOD-like receptor or NACHT,leucine-rich repeat (NLR) family of intracellular proteins. Several NLRs function in the innate immune system as sensors of pathogen components and participate in immune-mediated cellular responses via the caspase 1 inflammasome. Mutations in a gene related to NOD-2, NLRP3, are responsible for excess caspase 1,dependent interleukin-1, (IL-1,) in cryopyrinopathies such as Muckle-Wells syndrome. Furthermore, functional studies demonstrate that caspase 1,mediated release of IL-1, also involves NOD-2. The aim of this study was to test the hypothesis that IL-1, may mediate the inflammation seen in patients with Blau syndrome. Methods IL-1, release was measured in peripheral blood mononuclear cells cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15) mutation. Results We observed no evidence for increased IL-1, production in cells obtained from subjects with Blau syndrome compared with healthy control subjects. Furthermore, we presented 2 cases of Blau syndrome in which recombinant human IL-1 receptor antagonist (anakinra) was ineffective treatment. Conclusion Taken together, these data suggest that in contrast to related IL-1,,dependent autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL-1, or other IL-1 activity. [source] Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosisARTHRITIS & RHEUMATISM, Issue 1 2009Ikuo Okafuji Objective Blau syndrome and its sporadic counterpart, early-onset sarcoidosis (EOS), share a phenotype featuring the symptom triad of skin rash, arthritis, and uveitis. This systemic inflammatory granulomatosis is associated with mutations in the NOD2 gene. The aim of this study was to describe the clinical manifestations of Blau syndrome/EOS in Japanese patients and to determine whether the NOD2 genotype and its associated basal NF-,B activity predict the Blau syndrome/EOS clinical phenotype. Methods Twenty Japanese patients with Blau syndrome/EOS and NOD2 mutations were recruited. Mutated NOD2 was categorized based on its basal NF-,B activity, which was defined as the ratio of NF-,B activity without a NOD2 ligand, muramyldipeptide, to NF-,B activity with muramyldipeptide. Results All 9 mutations, including E383G, a novel mutation that was identified in 20 patients with Blau syndrome/EOS, were detected in the centrally located NOD region and were associated with ligand-independent NF-,B activation. The median age of the patients at disease onset was 14 months, although in 2 patients in Blau syndrome families (with mutations R334W and E383G, respectively) the age at onset was 5 years or older. Most patients with Blau syndrome/EOS had the triad of skin, joint, and ocular symptoms, the onset of which was in this order. Clinical manifestations varied even among familial cases and patients with the same mutations. There was no clear relationship between the clinical phenotype and basal NF-,B activity due to mutated NOD2. However, when attention was focused on the 2 most frequent mutations, R334W and R334Q, R334W tended to cause more obvious visual impairment. Conclusion NOD2 genotyping may help predict disease progression in patients with Blau syndrome/EOS. [source] Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15ARTHRITIS & RHEUMATISM, Issue 4 2007Mara L. Becker This is the first report of a CARD15 mutation,positive patient with Blau syndrome who exhibited interstitial lung disease, a feature historically considered absent from Blau syndrome, while typical of the adult form of sarcoidosis. This case illustrates the continued evolution of the phenotype of a disease initially conceived as a familial inflammatory granulomatous disease limited to the triad of synovitis, dermatitis, and uveitis. [source] CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathyARTHRITIS & RHEUMATISM, Issue 11 2002Xiaoju Wang Objective To analyze the CARD15 gene in families with heritable multi-organ granulomatoses, including the original Blau syndrome kindred as well as other families with related granulomatous conditions. Methods Linkage mapping was performed in 10 families. Observed recombination events were used to exclude regions centromeric or telomeric to 16q12.1, and the Blau gene critical region was refined to <3 cM, corresponding to a physical distance of 3.5 megabasepairs. Based on its known biochemical function, CARD15 was analyzed as a positional candidate for the Blau syndrome susceptibility gene, by direct DNA sequencing. Results These studies resulted in the identification, in 5 of the families, of 2 sequence variants at position 334 of the gene product (R334W and R334Q). Affected family members from the original Blau syndrome kindred were heterozygous for the R334W missense mutation; mutations at the same position were also observed in several unrelated Blau syndrome families, some of whose phenotypes included large-vessel arteritis and cranial neuropathy. The missense mutations segregated with the disease phenotype in the families, and were not seen in 208 control alleles. Conclusion These findings demonstrate that CARD15 is an important susceptibility gene for Blau syndrome and for other familial granulomatoses that display phenotypic traits beyond those of classic Blau syndrome. [source] 4252: An introduction to autoinflammatory syndromesACTA OPHTHALMOLOGICA, Issue 2010B BODAGHI To define the spectrum and pathophysiology of autoinflammatory syndromes. This term has been proposed to describe a new group of diseases characterized by attacks of seemingly unprovoked inflammation in the absence of pathogens, without significant levels of autoantibodies and autoreactive T cells. Hereditary periodic fever syndrome, Crohn's disease, Blau syndrome, Chronic infantile neurologic cutaneous and articular syndrome and Muckle-Wells syndrome are examples of autoinflammatory conditions characterized by recurrent attacks of inflammation without any association with auto-antigens. The study of autoinflammatory diseases has progressed from genetics to definition of the functional defects. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been established yet, this hypothesis remains highly plausible. Mutations in genes encoding the tumour necrosis factor (TNF) receptor and pyrin superfamilies of molecules may induce persistence of leukocytes that would ordinarily undergo apoptosis with further amplification of inflammatory stimuli. The use of biologics may control some of these conditions. [source] | ||||||||||