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.

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