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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

To explore the role of adhesion molecules in mediating mononuclear cell localisation, development of the granulomatous reaction, and cell mediated damage to the arterial wall in giant cell arteritis, 17 temporal artery biopsy specimens were examined. Eleven showed the histological features of giant cell arteritis and six showed no evidence of arteritis. All were examined for the expression of LFA-3, ICAM-1 and its receptor LFA-1, and HLA-DR. Temporal arteries with early features of arteritis, as well as histologically unaffected skip areas, showed a regional induction of ICAM-1 expression, but not HLA-DR, on smooth muscle cells of the media. ICAM-1 expression was detected in areas where a clinically important mononuclear cell infiltrate had not yet developed. In more florid cases of giant cell arteritis there was an additional widespread induction of ICAM-1 expression on intimal myofibroblasts. Strong expression of ICAM-1, HLA-DR, and LFA-3 was found on macrophages, epithelioid cells, and giant cells comprising the granulomatous lesion. The pattern of expression of these adhesion molecules suggests that they have a role in leucocyte traffic into the vascular lesion as well as in mediating the intercellular interactions which constitute the granulomatous response.
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PMID:Analysis of adhesion molecules in the immunopathogenesis of giant cell arteritis. 181 93

The results of investigations on the humoral immunological mechanisms are conflicting in giant cell arteritis (GCA) and have not been able to explain the pathological findings in the inflamed arterial wall. Altogether, immunological studies suggest that a cell-mediated immune reaction, possibly against an autologous antigen, occurs locally in the arteritic lesions of GCA. The excellent effect of treatment with glucocorticosteroids on the inflammation in GCA can also be explained by this model. The glucocorticosteroids inhibit the synthesis of interleukin-1 (IL-1) by the macrophages and suppress the IL-2 production from the T cells (Palacios, 1982). The observed HLA-DR expression in the arterial wall can be accounted for by the sum of macrophages and activated T cells, the macrophages being the most probable antigen-presenting cells. The interdigitating reticulum cells observed in some of the GCA patients may also be involved in antigen presentation. What the antigen(s) may be is, however, still unknown, as are the factors initiating the inflammatory process. It has recently been possible to extract T lymphocytes from the inflamed tissue and to culture these cells in vitro. After culture, it is possible to study the gene for the T-cell receptor, and probably even the antigenic specificity of the T cells. I hope that this approach may lead to a better understanding of the pathogenic mechanisms in GCA.
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PMID:Immunological studies in giant cell arteritis. 180 18

Peripheral blood lymphocytes from some patients with rheumatoid vasculitis and giant cell arteritis were cytotoxic in vitro towards endothelial cells, but not fibroblasts. Use of cell surface markers and cell density showed that cytotoxicity correlated with numbers of HLA-DR bearing cells, but not with cells bearing CD3, the transferrin receptor, or less dense lymphocytes. We concluded that activated, cytotoxic lymphocytes were present in the peripheral blood of a sub-set of patients with vasculitis.
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PMID:Activated, cytotoxic lymphocytes in systemic vasculitis. 183 18

To determine the phenotype of infiltrating mononuclear cells in patients with temporal arteritis (TA), we performed immunohistochemical studies on temporal artery biopsy specimens from 24 patients with biopsy-proven TA. Interdigitating reticulum cells (IRC) were observed in 41% of the patients; disease duration was significantly shorter in these patients than in patients lacking IRC (mean 1.5 months versus 3.8 months). Infiltrating cells consisted predominantly of HLA-DR-expressing macrophages and T lymphocytes, especially of the CD4 subset. There were few B cells and no K cells. No relationship between cellular distribution and disease duration or treatment was found. Interleukin-2 receptor expression was observed in 87.5% of biopsy specimens obtained prior to or within the first 4 days of treatment with prednisone, but in only 14% of specimens obtained later. The presence of IRC in patients with TA suggests an autoimmune reaction directed against an antigenic substance that resides in the arterial wall and is presented and processed in situ. DR-expressing macrophages activated by CD4+ T lymphocytes may contribute to arterial damage in TA. Corticosteroids do not modify cellular distribution but induce important functional changes, as demonstrated by the disappearance of interleukin-2 receptor expression in patients treated for more than 4 days.
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PMID:Immunohistochemical analysis of lymphoid and macrophage cell subsets and their immunologic activation markers in temporal arteritis. Influence of corticosteroid treatment. 278 41

HLA-DR antigen distribution was determined by lymphotoxicity on total lymphocytes for locus A.B.C. antigens numbering 14,28 and 7 respectively, and by a search on B lymphocytes for the 12 antigens of locus DR. The normal population included 124 subjects typed for HLA-A.B.C. and 200 subjects typed for HLA-DR. The frequency of alleles was compared to that of the different groups of patients. Significant variations were evaluated by the X2 test, using Woolf's method; the P value obtained was multiplied by the number of antigens looked for (P corrected, or pc). No deviation in frequency was found with the HLA-A.B.C. antigens. Only the DR 4 antigen, present in 23% of the normal population, was increased in proportions that depended on clinical classification: 39.4% (Pc = 0.05) in all patients with giant cell arteritis: 27% (NS) in the 37 polymyalgia rheumatica patients with negative biopsy of the temporal artery; 46.8% (P 0.05) in the 62 patients with Horton's disease presenting either as clinical and histological temporal arteritis (26 cases; DR 4 = 38.5%; NS), or as clinical and/or histological temporal arteritis associated with polymyalgia rheumatica (36 cases; DR 4 = 52.8%; Pc less than 0.005). The frequency of DR 4 antigen in Horton's disease with typical temporal artery biopsy (37 cases) was 46% (Pc = 0.05).
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PMID:[Distribution of HLA-DR antigens in unrelated giant cell arteritis]. 296 84

Immunohistochemical features of infiltrating mononuclear cells (MNC) and resident cells were studied in the temporal artery biopsy specimens of 13 patients with histological verified giant cell arteritis (GCA) and in six biopsy specimens from patients with GCA with negative histological findings. Eight temporal artery biopsy specimens from seven patients with unrelated diseases served as controls. In all patients with GCA proved by biopsy an infiltration of T lymphocytes in the arterial wall was observed, most being of the helper/inducer subset. No B lymphocytes, or very few, were seen. Lymphocytes in 10 out of the 13 positive biopsy specimens displayed staining for the class II major histocompatibility complex (MHC) antigen HLA-DR, whereas this was found in only two of eight controls. A minor number of the infiltrating T lymphocytes from seven out of 13 patients with GCA proved by biopsy stained for transferrin receptors, and in six out of the 13 cases they reacted with anti-interleukin 2 receptor antibody. In the arterial wall from all patients with histologically verified GCA we also found an increased number of macrophages, many of them expressing HLA-DR antigens and transferrin receptors. The immunohistochemical pattern of cell phenotypes found in the arterial wall of patients with GCA suggests that the infiltrating T cells are immunologically activated. This finding supports the hypothesis of a predominantly cellular immunological pathogenesis of giant cell arteritis.
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PMID:T cell subsets and expression of immunological activation markers in the arterial walls of patients with giant cell arteritis. 296 42

Giant cell arteritis (GCA) is a vascular inflammatory disease characterized by accumulations of T lymphocytes and macrophages in the arterial wall. In order to characterize the immune response in GCA, we have analysed temporal artery biopsies using a double-staining immunofluorescence method and studied T lymphocytes in peripheral blood with a fluorescence-activated cell sorter (FACS). HLA-DR was expressed on 28% (range 16-42%) of all T lymphocytes in the wall of the inflamed temporal artery, but only on average on 6% of peripheral blood T lymphocytes, indicating a high degree of local T cell activation in the inflammatory lesion. The proportions of T lymphocytes, T helper/inducer and T suppressor/cytotoxic cells in the blood of GCA patients before treatment with prednisolone did not deviate from those in normal individuals, but there was a minor increase in T helper cells after initiation of steroid therapy. The number of T helper cells expressing HLA-DR antigen and IL-2 receptor was not altered after 6-10 days of treatment with prednisolone. We found no evidence of HLA-DR expression by arterial smooth muscle cells in the GCA lesions, suggesting that these cells do not serve as antigen-presenting cells in GCA.
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PMID:HLA-DR expression in the vascular lesion and circulating T lymphocytes of patients with giant cell arteritis. 304 14

A 61-year-old woman, suffering from classic seropositive rheumatoid arthritis with rheumatoid nodule histologically documented, developed temporal arteritis. HLA-DR typing revealed the presence of DR3 and DR4 antigens. The findings from previous studies support the association of HLA-DR antigens, giant cell arteritis-polymyalgia rheumatica and rheumatoid arthritis, and suggest the participation of a common immunogenetic mechanism in their pathogenesis.
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PMID:Temporal arteritis in seropositive rheumatoid arthritis with rheumatoid nodule. 318 May 40

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


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