秦芳
中国医学科学院阜外医院 高血压中心
BACKGROUND:Establishing the diagnosis and determining disease activity of Takayasu arteritis (TA) remains challenging. Novel biomarkers might help to solve this problem.METHODS:In the screening phase, by using large-scale protein arrays detecting samples from 90 subjects (TA active, 29; TA inactive 31; and controls, 30). In the validation phase, by using enzyme-linked immunosorbent assay (ELISA), potential biomarkers for TA diagnosis, and activity classification were measured in independent cohorts, respectively.RESULTS:In the screening phase, 18 cytokines significantly differentially enriched between TA patients and controls and another 15 cytokines significantly differentially enriched between TA patient in active and inactive status were identified (adjusted P<0.05). In the validation phase, TIMP (tissue inhibitor of metalloproteinases)-1 was identified as a specific biomarker for TA diagnosis that a cutoff value of 221.86 μg/L could provide a specificity of 89.58% and a positive predictive value of 0.92. Meanwhile, we found it unreliable to use a single biomarker for TA activity classification. Considering this, we further built a logistic regression model based on multiple cytokines, including CA (cancer antigen) 125, FLRG (follistatin-related protein), IGFBP (insulin-like growth factor-binding protein)-2, CA15-3, GROa (growth-regulated alpha protein), LYVE (lymphatic vessel endothelial hyaluronic acid receptor)-1, ULBP (UL16-binding protein)-2, and CD (cluster of differentiation) 99, with an area under the curve reaching 0.909 for discriminating TA activity status.CONCLUSIONS:This study suggested TIMP-1 as a specific biomarker for TA diagnosis with a cutoff value of 221.86 μg/L. Furthermore, we provided a logistic regression model based on 8 biomarkers for the precisive activity classification of TA with an area under the curve of 0.909.
Circulation. Genomic and precision medicine 2019
The genetic factors related to early-onset hypertension are largely unknown. This study aimed to determine the spectrum of steroid metabolism gene variants and the clinical relationships of these variants to phenotypes in Chinese patients with early-onset hypertension. A total of 306 consecutive early-onset hypertensive patients were recruited. All coding exons and flanking intronic regions of KCNJ5, CYP11B1, and CYP17A1 were sequenced. Long-distance polymerase chain reaction was used to search for a CYP11B1/CYP11B2 chimeric gene. Pedigree investigations and genotype-phenotype analyses were performed for patients with rare variants. Nine rare variants were detected in eight patients (2.6%), but no CYP11B1/CYP11B2 chimeric gene was identified. One patient and two of her siblings were found to carry compound heterozygous mutations (C183Y and T390R) in CYP17A1 and were eventually diagnosed with atypical congenital adrenal hyperplasia. Patients with rare variants had younger ages of onset [17 (16, 20) vs. 30 (23, 35) years old, p = 0.010] and higher systolic blood pressure (148.5 ± 9.6 vs. 137.9 ± 17.8 mmHg, p = 0.021) than those without rare variants. Additionally, the patients and their relatives carrying rare variants exhibited increased serum free corticosterone [230.4 (7.4, 533.0) vs. 1.9 (0.9, 6.7)ng/ml, p = 0.001] and 11-deoxycorticosterone [16.16 (0.59, 33.23) vs. 0.77 (0.41, 0.96)ng/ml, p = 0.038] levels. Genetic testing is useful for the etiologic diagnosis of early-onset hypertension. Rare variants in steroid metabolism genes were associated with more severe clinical expression and abnormal circulating steroid metabolites in patients with early-onset hypertension.
Hypertension research : official journal of the Japanese Society of Hypertension 2019
OBJECTIVE:To describe the clinical features and longterm outcomes of patients with Takayasu arteritis (TA) in China who experienced neurological symptoms.METHODS:A retrospective study was undertaken of patients with TA who attended a single study center from 2002 to 2013, who also exhibited neurological symptoms (n = 274). Clinical and imaging features were analyzed, as well as longterm outcomes.RESULTS:The mean age at disease onset was 28.2 ± 11.2 years, with a female-to-male ratio of 4.3:1. The most common neurological manifestation was dizziness (214, 78.1%), the most frequent type of TA was type III (112, 40.9%), and the most common affected artery was the left subclavian (147, 53.6%). Involvement of 3 or 4 branches of the aortic arch was observed in 28% of patients. Among 30 patients experiencing a stroke (10.9%), steno-occlusive lesions of the subclavian artery and common carotid artery were frequently observed in patients with ischemic stroke, while steno-occlusive lesions of the descending aorta, abdominal aorta, and/or renal arteries were more frequently observed with hemorrhagic stroke. Heart failure was the most common cardiovascular event in those who died (n = 6) and in surviving cohorts.CONCLUSION:Neurological features in patients with TA were variable, and correlated with the number of arteries and the site of artery involvement. Resistant hypertension was one of the most important risk factors for hemorrhagic stroke in patients with TA.
The Journal of rheumatology 2015
OBJECTIVE:To describe a large cohort of patients with Takayasu arteritis in China.METHODS:We retrospectively analyzed 566 patients hospitalized in Fuwai Hospital between 2002 and 2013. Data collected were clinical characteristics, laboratory findings, angiographic features, treatment, and longterm outcome.RESULTS:The female to male ratio was 3.8 to 1, and the mean age of onset was 28.9 ± 12.0 years. The most common inflammatory symptom, initial symptom, and coexisting disease were fever (52, 9.2%), dizziness (214, 37.8%), and hypertension (HTN; 392, 69.3%), respectively. Pulmonary artery, coronary artery involvement, and aortic regurgitation were found in 83 (14.7%), 66 (11.7%), and 181 (36.7%) patients, respectively. Elevation of the erythrocyte sedimentation rate was observed in 131 patients (23.1%). Treatment included drugs, interventional therapy, autologous blood vessel transplant, artificial blood vessel transplant, and aortic valve replacement. During a mean followup of 5.0 ± 0.2 years, 32 patients died, including 1 patient who died suddenly during coronary angiography. HTN, major complications, and a progressive disease course were significant prognostic markers.CONCLUSION:HTN, rather than fever, is the leading reason for patients with Takayasu arteritis to see a doctor in China. HTN, major complications, and a progressive disease course are statistically significant predictors of survival. Because of cardiovascular events associated with the disease, early diagnosis and treatment are urgent to improve prognosis.
The Journal of rheumatology 2014
