In GCA, T cells, dendritic cells and macrophages form granulomatous lesions inside the vessel walls. CT angiography and magnetic-resonance angiography (MRA) help reveal the degree of disease and which arteries are involved. Disease tends to go into the aortic branches in a symmetrical pattern. As occlusion occurs, blocking off blood flow, blood tends to be rerouted to other vessels. Patients form aneurysms when disease leads to vessel destruction in the aorta, requiring surgical repair.
“We know that the disease leads to dissection, which we can rapidly diagnose. We know that when it dissects, it does so between the adventitia and the media, and forms a dissection lesion,” which can be fatal without intervention, Dr. Weyand showed. “So how does this vasculitic lesion come about? And how is this lesion connected to the extravascular component of disease? The GCA lesion has two major pathomechanisms. It has intimal hyperplasia and intimal myofibroblast proliferation that leads to the occlusion of the lumen. And it has neo-angiogenesis that sits mostly in the adventitia, and that’s what we capture when we image these patients.”
Inflammatory infiltrates in the media and adventitia have different composition. T cells are dominant in these lesions, and these T cells may produce IFN-γ, IL-17, IL-21, IL-9, IL-2 and IL-22, a highly diverse effector cell population that suggests multiple antigens are driving disease, “because so many different inflammatory cells are driving the lesion,” said Dr. Weyand. “What the lesion looks like from an immunological perspective is like it is unopposed, or to use a more modern term, like the immune response is ‘unleashed.’ So the question is how can this unleashed immune response get into a site that is normally protected by immune privilege—a site that nature had determined it does not want to have any inflammatory activity for any price?”