Insights into Pathogenesis of Takayasus Arteritis

Abstract

Takayasu's arteritis (TA) is an idiopathic large vessel inflammatory disease that predominantly affects young women. The pathology includes granulomatous changes. The inflammatory process favors the cervico-cranial vessels of the aortic arch, the thoracic more than the abdominal aorta and produces stenoses 4-5 times more often than aneurysms (Figure 1) [1,2]. Wider global recognition of TA has led to questioning of the accuracy of the longaccepted demographic of an Asian stereotype and the notion that the illness follows a triphasic (systemic, vascular inflammatory and burned out) course. Larger aggregate data has also increased appreciation of persistent disease activity, need for surgical remedies and a greater degree of disability than heretofore recognized. Recent insights into pathogenesis have led to experimental trials of novel therapies. This review will explore these insights and resultant changes in both medical and surgical interventions. Historical BackgroundThe first recognition of TA is most often credited to Mikito Takayasu (1905-Japanese Ophthalmology Society Annual Meeting). However, there are earlier descriptions of TA by G.B. Morgagni and William Savory [3,4]. In 1761 Morgagni described a 40 year old female who lost her radial pulses years before her death. Postmortem findings included subclavian obstruction and severe aortic changes characterized by ectasias, aneurysms and stenosis. In 1856 Savory described a 22 year old female with bruits over the left carotid artery and sternum as well as weak pulses in the femoral arteries. Postmortem examination revealed the inner layers of the arteries appeared to be thickened and have a 'wrinkled' appearance similar to what is called a 'tree barking' today. He noted that the arteries and not the veins were affected and collateralization can appear around obliterated segments. He reasoned that inflammation was the underlying cause and the disease likely progressed over long periods of time and could be asymptomatic. The detailed and insightful observations noted by both Morgagni and Savory deserve to be remembered. EpidemiologyMedian age at disease onset in most series is 25-30 years. Females are affected at least 8 times more often than males. [6] tend to be younger (mean age at diagnosis ~25 years) than patients in Italy and France (mean age at diagnosis ~ 30-40 years) [7,8]. Some investigators do not define TA as a disease of younger individuals and some series include elderly patients. The lack of consensus regarding age as a criterion produces bias in demographic comparisons. Cohorts in Japan, Korea, the United States, France and Italy [2,5,7,8,9] include ~80-90% females; those from India have about 60% females [10]. In Japan almost all patients are Japanese, in the US and Italy patients are predominantly Caucasian. Morbidity and MortalityWhile the five year survival of TA remains favorable (~94%), the disease related morbidity can be devastating. Claudication symptoms are common and affect activities of daily living in 60% of patients. Re...

Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients with Takayasu arteritis

“…The hypothesized mechanism of this association is shown in Figure-1. Although, statistically non-significant, AG genotype tended to be protective against the presence of aneurysms in TA, which are generally a consequence of rapid inflammation that outpaces fibrous remodelling process (5). It is likely that presence of G allele in AG genotype result in production of functionally ineffective IL-17F which cannot induce downstream endothelial inflammation and subsequent formation of aneurysm.…”

“…Cell-mediated immunity involving Th1, natural killer (NK), γδ T and Th17 cells, as well as various pro-inflammatory cytokines have been implicated in pathogenesis of TA (5). Decreased expression of interleukin-10 transcripts has also been observed in this illness.…”