Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting persons over 50 years of age. The inflammatory infiltrate, which is targeted at the aorta and its proximal branches, includes activated CD4+ helper T cells, histiocytes, and giant cells. To investigate whether the genetic polymorphism of the HLA-DRB1 genes contributes to the local accumulation of activated T cells, we have analyzed both HLA-DRB1 alleles in a cohort of 42 patients with biopsy-proven GCA. The majority of patients (60%) expressed the B1*0401 or B1*0404/8 variant of the HLA-DR4 haplotype, both of which also represent the major genetic factors underlying the disease association in RA. GCA patients negative for the disease-linked HLA-DR4 alleles were characterized by a nonrandom distribution of HLA-DRB1 alleles. Sequence comparison among the allelic products identified in the GCA cohort demonstrated heterogeneity for the sequence polymorphism of the third hypervariable region (HVR), but homology for the polymorphic residues within the HVR2 of the HLA-DRB1 gene. The GCA patients shared a sequence motif spanning amino acid positions 28-31 of the HLA-DR beta 1 chain. In the structural model for HLA-DR molecules, this sequence motif can be mapped to the antigen-binding site of the HLA complex, suggesting a crucial role of antigen selection and presentation in GCA. In contrast, the sequence polymorphism linked to RA has been mapped to the HVR3 of the HLA-DRB1 gene and translates into a distinct domain of the HLA-DR molecule, the alpha-helical loop surrounding the antigen-binding groove. A consecutive case series study demonstrated that GCA and RA rarely co-occurred, supporting the interpretation that distinct functional domains of the HLA-DR molecule are implicated in the pathomechanisms of these two autoimmune diseases.
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PMID:The HLA-DRB1 locus as a genetic component in giant cell arteritis. Mapping of a disease-linked sequence motif to the antigen binding site of the HLA-DR molecule. 146 92

We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls.
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PMID:HLA class II genes polymorphism in DR4 giant cell arteritis patients. 290 82

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr less than 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P less than 0.005). HLA-DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P less than 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.
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PMID:Polymyalgia rheumatica: a syndrome associated with HLA-DR4 antigen. 325 85

Giant cell arteritis developed in 2 brothers nearly simultaneously. They were positive for HLA-DR4 tissue antigen which has been associated with this disease. Both genetic and environmental factors may be important in the development of giant cell arteritis.
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PMID:Giant cell arteritis in two brothers. 348 85

Forty-three patients with well-documented giant cell arteritis (GCA) were studied clinically and with HLA typing. All patients were over age 40. Twenty-two of the patients had coexistent polymyalgia rheumatica (PMR). No association with class I HLA antigens was detected. When compared with HLA findings in 243 healthy controls, HLA-DR4 was increased in patients with GCA and PMR, but not in patients with GCA alone. Pooled analysis of data from 4 published papers confirmed the association of DR4 with GCA and PMR (P much less than 0.00001). Patients with PMR but negative findings of temporal artery biopsies also showed an increased frequency of HLA-DR4, but this did not reach statistical significance, probably because of the small number of subjects. It is likely that the increased frequency of DR4 in GCA patients is related to its association with PMR.
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PMID:HLA-DR4 in giant cell arteritis: association with polymyalgia rheumatica syndrome. 350 Jul 27

We reported the data of HLA-DR frequencies in a new series of 40 unrelated patients suffering from giant cells arteritis (Horton's disease). As previously reported by us, a large increase of HLA-DR4 antigen frequency is noted in patients compared with 146 healthy controls. Moreover, gathering together these 40 patients with the 48 other patients of our first published data, increase of the DR4 frequency is largely confirmed with a Pc less than 0.001.
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PMID:HLA DR4 and giant cell arteritis. 633 90

Precise information was obtained by a computerized analysis of the treatment, prognosis and clinical outcome of 108 representative cases selected from a series of 160 patients with Horton's disease (HD) diagnosed between 1970 and 1981. At the end of the study, 18 patients had died (16,6 p. 100), the commonest cause of death being a cerebrovascular accident. Death occurred during the first two years of the illness in half these cases. Despite these early complications of the disease, from a statistical point of view, the patients did not die of HD or the complications of its treatment. The 5 years survival rate 80,1 p. 100 (actuarial analysis). Most deaths were from natural causes; an intercurrent disease was often implicated; the lower probability of survival for men (69,9 p. cent at 5 years, compared to 85,4 p. cent for women) is compatible with the lower life expectancy which is well established. The roles of intercurrent disease and sex were statistically significant. On the other hand, there was no difference in the probability of 5 year survival when the different presenting of the disease, the terrain (HLA-DR4) and choice of corticosteroid therapy were compared. The initial dose of prednisone or prednisolone should exceed 0,5 mg/kg/day, if relapse is to be avoided. No additional benefits were observed with doses in excess of 1 mg/kg/day except in cases with complications from the onset (ocular, coronary insufficiency, stenosis of the main large arteries, without being able to prejudge their mechanism).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Outcome, treatment and prognosis of Horton's disease]. 665 Oct 63

HLA-DR locus antigens were determined in 69 patients with giant cell arteritis, polymyalgia rheumatica, or both. The frequencies of HLA-DR4 and HLA-DRW6 in these patients were increased above normals. But the differences were not significant in the total group nor when the patients were separated according to the presence or absence of polymyalgia rheumatica.
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PMID:HLA-DR locus antigens in polymyalgia rheumatica and giant cell arteritis. 694 60

Giant cell arteritis is a form of vasculitis affecting medium- and large-size arteries, with a predilection for vessels arising from the aortic arch. The origins of giant cell arteritis are unknown. However, ethnic affinities are prominent, with the majority of cases involving white, elderly patients. In addition, there is evidence of a familial pattern and an association with HLA-DR4, suggesting a genetic predisposition in select cases. With an increase in the elderly population, clinicians must become cognizant of this age-related malady and its treatment to ensure quality care for elderly patients.
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PMID:Giant cell arteritis. 792 1

We report on two siblings with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). Temporal artery biopsies revealed GCA in three cases, and sclerosis of the wall of the temporal artery in one case. The HLA haplotype was identical in the first pair, and in the second pair HLA-A2, HLA-B39 and HLA-DR53 were identical. In three patients HLA-DR4 was demonstrated. Cases of familial aggregation of GCA have been reported in the literature. In several reports an increased prevalence of HLA-DR4 was described (about 40% of patients with GCA, compared with about 13% in the European population). HLA-DR4 was observed in three of our four patients and a haploidentity was found in one pair. Based on our observation and the results published in the literature, it seems probable that giant cell arteritis--a typical disease of advanced age--has at least partially a genetic basis.
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PMID:[Giant cell arteritis--a genetically-determined disease?]. 797 27


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