Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wegener's granulomatosis (WG) and microscopic polyangiitis are systemic autoimmune diseases characterized by the presence of ANCA in the sera of patients. Little is known about the aetiologic factors and genetic predisposition as well as the pathogenesis of these disease entities. A slightly decreased representation of HLA-DRB1*13 and HLA-DQB1*0603 individuals was observed in our cohort of ANCA-associated systemic vasculitis (AASV) patients compared with controls. In addition, HLA-DRB1*04 individuals were over-represented in a subgroup of patients with WG in end-stage renal disease as a result of renal vasculitis. In order to identify other genes relevant for these diseases, we investigated highly polymorphic markers in the vicinity of several immunorelevant genes, i.e. tumour necrosis factor (TNF)alpha, IL-2, IL-5 receptor alpha (IL-5RA), in a group of 102 patients with AASV and compared the representation with controls. Furthermore, functional polymorphisms were directly analysed in the promotor region of TNFalpha as well as in the coding region of the FcgammaIIRA genes. Polymorphisms of the TNFalpha promotor (TNF-308) as well as in the FcgammaIIRA gene were excluded as risk factors for the disease in our cohort. No major phenotype distribution differences were observed between patients and controls for the IL-2 and IL-5RA microsatellites. Most importantly, several haplotypes on chromosome 6p appeared strongly associated with proteinase 3 (PR3)-ANCA+ AASV. Thus, as in other autoimmune diseases, different predisposing factors play differential aetiopathogenic roles in various groups of AASV patients.
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PMID:Immunogenetic risk factors for anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis. 1044 78

Giant cell (temporal) arteritis (GCA) is the most common systemic vasculitis in Western countries. It involves large and medium-sized vessels with predisposition to the cranial arteries in the elderly. Cranial ischemic complications, in particular permanent visual loss, constitute the most feared aspects of this vasculitis. Although the use of corticosteroids and a higher physician awareness may have contributed to a decrease in the frequency of severe ischemic complications, permanent visual loss is still present in 7%-14% of patients. To investigate further the incidence, trends, and clinical spectrum of visual manifestations in patients with GCA, we examined the features of patients with biopsy-proven GCA diagnosed at the single reference hospital for a defined population in northwestern Spain during an 18-year period. Predictive factors for the development of any visual manifestation, not only permanent visual loss, were also examined. Between 1981 and 1998, 161 patients were diagnosed with biopsy-proven GCA. Visual ischemic complications were observed in 42 (26.1%), and irreversible blindness, mainly due to anterior ischemic optic neuropathy and frequently preceded by amaurosis fugax, was found in 24 (14.9%). Despite a progressive increase in the number of new cases diagnosed, there was not a significant change in the proportion of patients with visual manifestations during the study period (p = 0.37). Patients with visual ischemic complications had lower clinical and laboratory biologic markers of inflammation. Indeed, during the last years of the study, anemia was associated with a very low risk of visual complications. Also, HLA-DRB1*04-positive patients had visual manifestations more commonly. Patients with other ischemic complications developed irreversible blindness more frequently. The best predictors of any visual complication were HLA-DRB1*04 phenotype (odds ratio [OR] 7.47) and the absence of anemia at the time of admission (OR for patients with anemia = 0.07). The best predictors of irreversible blindness (permanent visual loss) were amaurosis fugax (OR 12.63) and cerebrovascular accidents (OR 26.51). The present study supports the claim that ocular ischemic complications are still frequent in biopsy-proven GCA patients from southern Europe. The presence of other ischemic complications constitutes an alarm for the development of irreversible blindness. In contrast, a higher inflammatory response may be a protective factor against the development of cranial ischemic events.
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PMID:Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients. 1103 76

The objective of this study was to examine HLA-DRB1 and HLA-DQB1 genotypes in patients with severe extra-articular rheumatoid arthritis (ExRA) and to compare them with the genotypes of rheumatoid arthritis (RA) patients without extra-articular manifestations. Patients with severe ExRA were recruited from a large research database of patients with RA, from two cohorts of prevalent RA cases, and from a regional multicenter early RA cohort. Cases with ExRA manifestations (n = 159) were classified according to predefined criteria. Controls (n = 178) with RA but no ExRA were selected from the same sources. Cases and controls were matched for duration of RA and for clinical center. PCR based HLA-DRB1 and HLA-DQB1 genotyping was performed using the Biotest SSP kit, with additional sequencing in order to distinguish DRB1*04 subtypes. Associations between alleles and disease phenotypes were tested using multiple simulations of random distributions of alleles. There was no difference in global distribution of HLA-DRB1 and HLA-DQB1 alleles between patients with ExRA and controls. DRB1*0401 (P = 0.003) and 0401/0401 homozygosity (P = 0.002) were more frequent in Felty's syndrome than in controls. The presence of two HLA-DRB1*04 alleles encoding the shared epitope (SE) was associated with ExRA (overall odds ratio 1.79, 95% confidence interval 1.04-3.08) and with rheumatoid vasculitis (odds ratio 2.44, 95% confidence interval 1.22-4.89). In this large sample of patients with ExRA, Felty's syndrome was the only manifestation that was clearly associated with HLA-DRB1*0401. Other ExRA manifestations were not associated with individual alleles but with DRB1*04 SE double dose genotypes. This confirms that SE genes contribute to RA disease severity and ExRA. Other genetic and environmental factors may have a more specific impact on individual ExRA manifestations.
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PMID:The impact of HLA-DRB1 genes on extra-articular disease manifestations in rheumatoid arthritis. 1654 68

Important steps forwards have been taken during recent years towards the understanding of the genetic basis of autoimmunity. The increasing number of study cohorts is allowing better characterization of the genetic component of most autoimmune diseases. However, the molecular mechanisms leading to some less common diseases remain poorly understood. GCA, an antigen-driven systemic vasculitis affecting medium and large blood vessels of elderly people, represents one of these cases. However, although underpowered to detect low to moderate effect sizes and without replication steps, many genetic studies on this disease have been published in the past decade. These reports clearly point to genes located in the MHC region, in particular HLA-DRB1*04 alleles, and other key members of the immune and inflammatory response (including cytokines, adhesion molecules and regulators of innate immunity), as crucial players in the development and progression of GCA. Considering that no literature review has been published so far about the genetic component of this vasculitis, we aimed to summarize here the current knowledge on the genetics underlying GCA predisposition and severity.
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PMID:Genetic component of giant cell arteritis. 2384 9

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disorder, belonging to the small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, defined as an eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium-sized vessels, associated with asthma and eosinophilia. EGPA pathogenesis is not well known: HLA-DRB1*04 and *07, HLA-DRB4 and IL10.2 haplotype of the IL-10 promoter gene are the most studied genetic determinants. Among the acquired pathogenetic factors, the exposure to different allergens, infections, vaccinations, drugs, and silica exposure have been involved. Eosinophils are the most characteristic cells in EGPA and different studies have demonstrated their role as effector and immunoregulatory cells. EGPA is considered as a disease with a prevalent activation of the Th-2 cellular-mediated inflammatory response and also humoral immunity plays an important role. A link between B and T inflammatory responses may explain different disease features. EGPA typically develops into three sequential phases: the allergic phase, distinguished by the occurrence of asthma, allergic rhinitis, and sinusitis, the eosinophilic phase, in which the main pathological finding is the eosinophilic organ infiltrations (e.g., lungs, heart, and gastrointestinal system), and the vasculitic phase, characterized by purpura, peripheral neuropathy, and constitutional symptoms. ANCA (especially pANCA anti-myeloperoxidase) are present in 40-60% of the patients. An elevation of IgG4 is frequently found. Corticosteroids and cyclophosphamide are classically used for remission induction, while azathioprine and methotrexate are the therapeutic options for remission maintenance. B-cell depletion with rituximab has shown promising results for remission induction.
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PMID:Eosinophilic granulomatosis with polyangiitis: an overview. 2540 30