The etiology of PMR and GCA is unknown. They are autoimmune disorders that may be triggered by exogenous factors, particularly infection in genetically susceptible individuals. HLA-DR4 antigens are present in roughly twice as many patients with GCA as in controls, and there is evidence that HLA class II-restricted CD4 positive-activated helper cells drive the disease (2). CD8-positive T-lymphocyte counts appear to be lower in patients with PMR and GCA.

The cell-mediated, antigen-driven response in GCA occurs in the arterial wall. There is T-cell activation likely to an antigen in the arterial wall, although it is not known whether this is exogenous, such as a viral product, or a component of the artery itself. The result is a granulomatous inflammation with giant cells, particularly at the intima and medial junction, seen in about 50% of cases. The remaining 50% of patients have a panarteritis with a mixed cell inflammatory infiltrate of lymphocytic and mononuclear cells and some neutrophils and eosinophils, without giant cells being present.

Antigen is recognized in the adventitia by T-cells that undergo clonal expansion and produce interferon-g. This results in the differentiation and migration of macrophages and formation of giant cells. In the adventitia, macrophages produce interleukin (IL)-1 and IL-6; in the media, macrophages produce metalloproteinases; and in the intima, nitric oxide along with platelet-derived growth factor and vascular endothelial growth factor repair efforts destroy the vessel wall. Resultant inflammation of the arteries of the aortic arch and the primary branches causes focal and segmental disruption of the internal elastic lamina. Some patients with GCA have minimal systemic inflammatory disease with primary ischemic manifestations, while others have mainly PMR-related symptoms. The clinical variations in disease are correlated with local expression of cytokine messenger RNA (4). Ischemic symptoms occur with high levels of interferon-g and IL-1B. Patients with fever tend to have low levels of interferon-g, and patients with PMR and large vessel arteritis including aortitis have higher levels of IL-2.

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