Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients.
- 作者列表："Lubbers R","Sutherland JS","Goletti D","de Paus RA","Dijkstra DJ","van Moorsel CHM","Veltkamp M","Vestjens SMT","Bos WJW","Petrone L","Malherbe ST","Walzl G","Gelderman KA","Groeneveld GH","Geluk A","Ottenhoff THM","Joosten SA","Trouw LA
BACKGROUND:To facilitate better discrimination between patients with active tuberculosis (TB) and latent TB infection (LTBI), whole blood transcriptomic studies have been performed to identify novel candidate host biomarkers. SERPING1, which encodes C1-inhibitor (C1-INH), the natural inhibitor of the C1-complex has emerged as candidate biomarker. Here we collated and analysed SERPING1 expression data and subsequently determined C1-INH protein levels in four cohorts of patients with TB. METHODS:SERPING1 expression data were extracted from online deposited datasets. C1-INH protein levels were determined by ELISA in sera from individuals with active TB, LTBI as well as other disease controls in geographically diverse cohorts. FINDINGS:SERPING1 expression was increased in patients with active TB compared to healthy controls (8/11 cohorts), LTBI (13/14 cohorts) and patients with other (non-TB) lung-diseases (7/7 cohorts). Serum levels of C1-INH were significantly increased in The Gambia and Italy in patients with active TB relative to the endemic controls but not in South Africa or Korea. In the largest cohort (n = 50), with samples collected longitudinally, normalization of C1-INH levels following successful TB treatment was observed. This cohort, also showed the most abundant increase in C1-INH, and a positive correlation between C1q and C1-INH levels. Combined presence of increased levels of both C1q and C1-INH had high specificity for active TB (96 %) but only very modest sensitivity 38 % compared to the endemic controls. INTERPRETATION:SERPING1 transcript expression is increased in TB patients, while serum protein levels of C1-INH were increased in half of the cohorts analysed.
背景: 为了更好地区分活动性结核病 (TB) 和潜伏性结核感染 (LTBI) 患者，进行了全血转录组学研究，以确定新的候选宿主生物标志物。SERPING1 编码C1-inhibitor (C1-INH)，是C1-complex的天然抑制剂，已成为候选生物标志物。在这里，我们整理并分析了SERPING1 表达数据，随后测定了 4 个队列TB患者的C1-INH蛋白水平。 方法: 从在线保存的数据集中提取SERPING1 表达数据。在不同地理位置的队列中，通过ELISA测定活动性TB、LTBI以及其他疾病对照个体血清中的C1-INH蛋白水平。 结果: 与健康对照 (8/11 个队列) 、LTBI (13/14 个队列) 和其他 (非TB) 患者相比，活动性TB患者的SERPING1 表达增加肺部疾病 (7/7 个队列)。在冈比亚和意大利，活动性结核病患者的血清C1-INH水平显著高于当地对照组，而在南非和韩国则没有。在最大的队列 (n = 50) 中，纵向收集样本，观察到成功结核病治疗后C1-INH水平正常化。该队列也显示出最丰富的C1-INH增加，C1q与C1-INH水平呈正相关。C1q和C1-INH水平升高的联合存在对活动性结核病具有较高的特异性 (96%)，但与地方病对照组相比，只有非常有限的敏感性 38%。 解释: SERPING1 转录表达在结核病患者中增加，而在分析的队列中有一半的C1-INH血清蛋白水平增加。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.