Molecular approaches toward pathologic mechanisms in giant cell arteritis and Takayasu's arteritis.
Molecular techniques have provided new tools to define genetic systems involved in disease susceptibility and to dissect molecular events driving inflammatory reactions. Inflammatory infiltrates in the wall of large and medium-sized arteries, sometimes associated with giant cell formation, are pathognomic for Takayasu's arteritis (TA) and giant cell (cranial) arteritis. Molecular techniques have been used successfully to define genetic host factors involved in disease susceptibility and to dissect the nature of inflammatory cells and mediators in the pathologic lesions. Careful analysis of incidence data for TA suggests that TA is a worldwide disease. Genetic comparison of western and eastern TA, however, raises the possibility of disease heterogeneity. Emerging data indicate that HLA-DRB1 genes represent important risk factors in giant cell arteritis. Whether disease association is related to the role of HLA-DR molecules in presenting a disease-inducing antigen remains to be seen. Analysis of the molecular diversity of tissue-infiltrating T cells indicates that a small proportion of CD4+ T cells proliferate in situ, potentially as a result of antigen recognition. Tissue cytokine profiles reveal functional selection of T cells and are compatible with the model that Th1 cells recognize antigen on the surface of activated macrophages. The presence of T cell-derived cytokines in temporal artery tissue of patients with polymyalgia rheumatica who are lacking microscopic inflammation indicates subclinical vasculitis.
Weyand
C M
CM
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Goronzy
J J
JJ
D016207:Cytokines / Q000502:physiology; D005821:Genetic Techniques; D013700:Giant Cell Arteritis / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D014943:Global Health; D006801:Humans; D015995:Prevalence; D013601:T-Lymphocytes / Q000502:physiology; D013625:Takayasu Arteritis / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*
D016207:Cytokines