Abstract
7. ABSTRACT Introduction: Takayasu arteritis (TA) is a rare form of systemic vasculitis, predominantly affecting aorta and its main branches. It has a world wide distribution with a variable prevalence and disease expression. The geographic distribution of the disease suggests ethnic influences on susceptibility and clinical manifestations of TA. HLA alleles are implicated as important genetic predisposing factors for TA which are known to be polymorphic and show significant ethnic variations in allele and haplotype frequencies^ The aim of this study was to investigate the clinical and angiographic findings and the DNA sequencing of HLA-B alleles of TA patients from various regions in Turkey. Materials and Methods: Seventy one patients (F/M: 63/8, mean age at diagnosis: 32.3 years) were diagnosed with TA according to the angiograms (Classification of International Conference on TA- Tokyo, 1994) and fulfilled the 1990 classification criteria of ACR. Patients' clinical and angiographic findings were assessed according to a predefined protocol. The patients were followed multicentrally at different Departments of Rheumatology at Turkey. DNA samples that were isolated from blood samples of 68 patients with TA and 191 healthy controls were studied using genotyping after PCR amplification with sequence specific oligonucleotide probes and B*51 and B*52 were verified by sequence specific priming. 73Results: Most common clinical findings were the absence or weakness of pulses (85 %), pain in the extremites (71 %) and hypertension (43 %). Central nervous system manifestations due to vascular insufficiency occurred in 27 patients (38 %), 13 of whom developed ischemic cerebro-vascular disease. Other common symptoms were renal artery stenosis (32 %), erythema nodosum (15,4 %), visual disturbances (19,7 %), aortic insufficiency (18,3 %) and pulmonary hypertension (5,6 %). Angiographic findings in 71 patients revealed that 46.2 % of the patients were type I, 44 % type V, 4.4 % type Ha and one patient each type lib and III. Subclavian artery was the most commonly involved (38 %) and stenosis was the most common lesion. A total of 26 patients (33 %) had undergone angioplasty procedures. One patient had pulmonary tuberculosis. %43 out of 43 patients developed a delayed skin reactivity to PPD, 5 of whom had a history of house-hold tuberculosis. 90 %of ail patients are currently on steroid therapy. In addition to steroid therapy, 50 % are taking methotrexate (MTX) and 18% are taking azathiopirin (AZA). Among the HLA-B alleles only B*52 has shown a significant association with TA: 13/70 vs. 13/191, p=0.009, OR: 3.1. There was no association betweeen B*52 and any particular clinical manifestation or the angiographic classifications of TA, however, there was significant association between B*52 and aortic regurgitations (P<0,02 ). Conclusion: Types III and IV are uncommon in TA patients from Turkey, probably explaining the lower frequencies of renal artery stenosis and 74hypertension compared to other series. PPD positivity and active tuberculosis were also not frequently observed. Combination therapy with MTX or AZA are more commonly prescribed compared to earlier series. The previously reported association of TA with B*52 in Japanese, Thai and Korean population has been confirmed in Turkish patient. Repeatedly demostrated association with B*52 might have implications about functional relevance of this molecule in TA, which has to be determined. 75
