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Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families, structure, and functions has improved in recent decades. Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions. Currently, modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.  相似文献   
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IntroductionMonoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021.MethodsAccording to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan.ResultsDuring Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12–0.53) and 0.10 (95% CI: 0.01–0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event.ConclusionsThe administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.  相似文献   
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Vaccination generates a neutralizing immune response against SARS-CoV-2. The genomic surveillance is showing the emergence of variants with mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we report the neutralization potency against alpha, gamma, and D614G SARS-CoV-2 variants in 44 individuals that received two doses of CoronaVac vaccine, an inactivated SARS-CoV-2 vaccine. Plasma samples collected at 60 days after the second dose of CoronaVac were analyzed by the reduction of cytopathic effect in Vero E6 cells with the three infectious variants of SARS-CoV-2. Plasma showed lower neutralization with alpha (geometric mean titer [GMT] = 18.5) and gamma (GMT = 10.0) variants than with D614G (GMT = 75.1) variant. Efficient neutralization against the alpha and gamma variants was not detected in 31.8% and 59.1% of plasma, respectively. These findings suggest the alpha and gamma variants could escape from neutralization by antibodies elicited by vaccination. Robust genomic and biological surveillance of viral variants could help to develop effective strategies for the control of SARS-CoV-2.  相似文献   
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Antiphospholipid syndrome (APS) is an autoimmune disease and one of the most common causes of acquired thrombophilia. It is characterised by the occurrence of thrombotic or obstetric events associated with the presence of persistent antiphospholipid antibodies. The diagnosis can be challenging, particularly because some biological tests can be disturbed by anticoagulant treatment or inflammation.In the recent years, new antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT), have emerged but their clinical significance and causality remain uncertain.Biologically, several studies have found a strong correlation between the presence of lupus anticoagulant (LA) and anti-PS/PT antibodies. Clinically, the presence of anti-PS/PT antibodies is associated with an increased risk of thrombosis and obstetric complications. There is also an association with thrombocytopenia, suggesting that the presence of anti-PS/PT antibodies may be associated with more severe clinical APS. Among seronegative APS patients, 6–17% of patients are positive for anti-PS/PT antibodies. This might influence the therapeutic management of patients.This article aims to provide an update on contribution of anti-PS/PT antibodies detection for the diagnosis and management of APS.  相似文献   
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抗体药物具有特异性高、不良反应少的特点,已成为肿瘤治疗的热点。双特异性抗体(双抗)是指同时结合2个不同抗原或同一抗原2个表位的抗体。与单特异性抗体相比,双抗具有高度特异性,增强了治疗有效性和安全性,同时减少了不良反应。已有多种双抗药物获批上市,进入临床研究的双抗药物数量不断增加。双抗药物的形式持续在更新,应用范围也在扩大,在未来具有非常好的应用前景。此文就目前已有的双抗类型、作用机制及目前双抗制备上面临的困难等进行概述。  相似文献   
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《Saudi Pharmaceutical Journal》2022,30(12):1736-1747
Cystic fibrosis (CF) is a genetic disease that affects the exocrine glands and is caused by cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. Lung disease is the leading cause of morbidity in patients. Target-specific treatment of CF has been achieved using monoclonal antibodies (mAbs). The purpose of this article is to discuss the possibility of treating CF with mAbs through their significant target specificity. We searched electronic databases in Web of Science, PubMed, EMBASE, Scopus, and Google Scholar from 1984 to 2021. We discussed the critical role of targeted therapy in cystic fibrosis, as it will be more effective at suppressing the molecular networks. After conducting a critical review of the available literature, we concluded that it is critical to understand the fundamental molecular mechanisms underlying CF prior to incorporating biologics into the therapy regimen. Omalizumab, Mepolizumab, Benralizumab, Dupilumab and KB001-A have been successfully screened for asthma-complicated CF, and their efficacies have been well reported. Despite the availability of effective targeted biologics, treating CF has remained a difficult task, particularly when it comes to reduction of secondary inflammatory mediators. This review emphasizes the overall views on CF, the immunological mechanism of CF, and the prospective therapeutic use of mAbs as potential targeted biologics for enhancing the overall status of human health.  相似文献   
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