- 作者列表："Maccora, Ilaria","Calabri, Giovanni Battista","Favilli, Silvia","Brambilla, Alice","Trapani, Sandra","Marrani, Edoardo","Simonini, Gabriele
To describe clinical and epidemiological characteristics of a Kawasaki syndrome cohort. In a monocentric, retrospective, observational study, between February 1982 and August 2018, we enrolled 361 children, aged 1 month to 24.4 years. Coronary artery lesions were detected in 20.2% of patients: 16% had coronary ectasia, and 4.15% had coronary aneurisms. A significant difference regarding age at disease onset ( p = 0.025), fever duration ( p < 0.0001), CRP ( p = 0.001) and day of first IVIG administration ( p < 0.0001) was detected among group. A significant correlation between coronary artery lesions and disease onset < 6 months ( p = 0.009), second IVIG dose ( p < 0.001) and male gender ( p = 0.038) has been detected. Median long-term follow-up was 10.2 years (1–36 years). At the last available follow-up, patients without coronary involvement and coronary ectasia had normal cardiological tests, conversely, in patients with aneurisms, 8/13 showed persistent aneurisms at echocardiography, one ECG repolarization alterations, and one ST depression at the peak of effort during ergometric test. Conclusion : Children with lower age, longer fever, higher level of CRP and retard in IVIG administration are at higher risk to develop coronary artery lesions. Our long-term follow-up analysis confirms, over 36 years of observation, the benign course of Kawasaki syndrome even in coronary artery lesion patients, if timely treated. What is already known about this topic? • Stopping cardiologic assessment in no risk patients results economically advantageous, timesaving and able to reduce emotional discomfort in children and their families. • Age at disease onset, fever duration, CRP level, and day of first IVIG administration are possible risk factors for coronary artery lesions What is New? • During 36 years of observation in real life, our study shows the benign course of Kawasaki syndrome without coronary artery lesions after 6–8 weeks from the disease onset. • Age < 6 months at disease onset is strongly related with coronary artery lesion development.
描述川崎综合征队列的临床和流行病学特征。在 1982 年 2 月至 2018 年 8 月的一项单中心、回顾性、观察性研究中，我们招募了 361 名 1 个月至 24.4 岁的儿童。20.2% 的患者检出冠状动脉病变: 16% 有冠状动脉扩张，4.15% 有冠状动脉瘤。发病年龄 (p = 0.025) 、发热持续时间 (p <0.0001) 、 CRP ( p = 0.001) 差异有统计学意义检测各组间 IVIG 首次给药日 (p <0.0001)。冠状动脉病变与发病 <6 个月 (p = 0.009) 、第二次 IVIG 剂量 (p <0.001) 显著相关男性 (p = 0.038) 已检出。中位长期随访时间为 10.2 年 (1-36 年)。在最后一次随访中，无冠状动脉受累和冠状动脉扩张的患者心脏检查正常，相反，在动脉瘤患者中，8/13 的患者在超声心动图上显示持续动脉瘤，一次心电图复极改变,在测力计测试过程中，在努力的高峰期出现一次抑郁。结论: 年龄较小、发热时间较长、 CRP 水平较高、 IVIG 使用时间较长的患儿发生冠状动脉病变的风险较高。我们的长期随访分析证实，超过 36 年的观察，即使在冠状动脉病变患者川崎综合征的良性过程，如果及时治疗。关于这个话题已经知道了什么？•在无风险患者中停止心脏评估，结果经济上有利，省时，能够减少儿童及其家庭的情绪不适。•发病年龄、发热持续时间、 CRP 水平和首次 IVIG 给药日期是冠状动脉病变的可能危险因素。什么是新的？•在现实生活中 36 年的观察中，我们的研究显示了从发病 6-8 周后无冠状动脉病变的川崎综合征的良性病程。•发病年龄 <6 个月与冠状动脉病变发展密切相关。
METHODS:Novel interventions that do not rely on daily adherence to ART are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong ART. Considering the risks and expense associated with ART interruption trials, the identification of biomarkers of viral rebound will prioritize promising therapeutic intervention strategies, including anti-HIV Env protein therapeutics. However, comprehensive studies to identify those biomarkers are logistically challenging in human infants, demanding the need for relevant nonhuman primate models of HIV rebound. In this study, we developed an infant RM model of oral infection with simian-human immunodeficiency virus expressing clade C HIV Env and short-term ART followed by ATI, longitudinally characterizing the immune responses to viral infection during ART and after ATI. Additionally, we compared this infant RM model to an analogous adult RM rebound model and identified virologic and immunologic correlates of the time to viral rebound after ATI.To achieve long-term viral remission in human immunodeficiency virus (HIV)-infected children, novel strategies beyond early antiretroviral therapy (ART) will be necessary. Identifying clinical predictors of the time to viral rebound upon ART interruption will streamline the development of novel therapeutic strategies and accelerate their evaluation in clinical trials. However, identification of these biomarkers is logistically challenging in infants, due to sampling limitations and the potential risks of treatment interruption. To facilitate the identification of biomarkers predicting viral rebound, we have developed an infant rhesus macaque (RM) model of oral simian-human immunodeficiency virus (SHIV) SHIV.CH505.375H.dCT challenge and analytical treatment interruption (ATI) after short-term ART. We used this model to characterize SHIV replication kinetics and virus-specific immune responses during short-term ART or after ATI and demonstrated plasma viral rebound in 5 out of 6 (83%) infants. We observed a decline in humoral immune responses and partial dampening of systemic immune activation upon initiation of ART in these infants. Furthermore, we monitored SHIV replication and rebound kinetics in infant and adult RMs and found that both infants and adults demonstrated equally potent virus-specific humoral immune responses. Finally, we validated our models by confirming a well-established correlate of the time to viral rebound, namely, the pre-ART plasma viral load, as well as identified additional potential humoral immune correlates. Thus, this model of infant ART and viral rebound can be used and further optimized to define biomarkers of viral rebound following long-term ART as well as to preclinically assess novel therapies to achieve a pediatric HIV functional cure.
METHODS:There is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by antibodies directed to NA remain largely unexplored. Herein, we show that antibody Fc interaction with Fcγ receptors (FcγRs) expressed on effector cells contributes to viral control in a murine model of influenza. Importantly, a chimeric mouse-human IgG1 with no direct antiviral activity was demonstrated to solely rely on FcγRs to protect mice from disease. Therefore, antibodies without NA enzymatic inhibitory activity may also play a role in controlling influenza viruses and should be of consideration when designing NA-based vaccines and assessing immunogenicity.Influenza virus neuraminidase (NA) has been under intense study recently as a vaccine antigen, yet there remain unanswered questions regarding the immune response directed toward NA. Antibodies (Abs) that can inhibit NA activity have been shown to aid in the control of disease caused by influenza virus infection in humans and animal models, yet how and if interactions between the Fc portion of anti-NA Abs and Fcγ receptors (FcγR) contribute to protection has not yet been extensively studied. Herein, we show that poly- and monoclonal anti-NA IgG antibodies with NA inhibitory activity can control A(H1N1)pdm09 infection in the absence of FcγRs, but FcγR interaction aided in viral clearance from the lungs. In contrast, a mouse-human chimeric anti-NA IgG1 that was incapable of mediating NA inhibition (NI) solely relied on FcγR interaction to protect transgenic mice (with a humanized FcγR compartment) against A(H1N1)pdm09 infection. As such, this study suggests that NA-specific antibodies contribute to protection against influenza A virus infection even in the absence of NI activity and supports protection through multiple effector mechanisms.
METHODS:Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in in utero transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education.