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

Emerging data support the model that giant cell arteritis (GCA) is an antigen-driven disease. Select helper T cells are recruited to the vascular lesions where they produce a defined pattern of cytokines. At least two functionally distinct populations of macrophages are involved and macrophage activation extends into the compartment of circulating phagocytes. Searches for the antigen may be facilitated through structural analysis of specially activated T lymphocytes in the lesions. In addition to the proposed disease-inducing agent, genetic risk factors are important. One of the genetic elements has been mapped to the HLA-DR region and seems to encode parts of a pocket in the HLA-DR molecule, accommodating side chains of the interacting antigenic peptide. On the molecular level, some but not all pathomechanisms are shared by polymyalgia rheumatica and GCA, indicating that both syndromes form a spectrum of disease.
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PMID:Giant cell arteritis as an antigen-driven disease. 859 35