Monoclonal antibody against human Tim‐3 enhances antiviral immune response

T cell immunoglobulin and mucin domain protein 3 (Tim‐3) is an immune checkpoint inhibitor in T cells and innate immune cells. The deregulated upregulation of Tim‐3 is related to immune exhaustion in tumour and viral infection. To overcome Tim‐3‐mediated immune tolerance, we developed a novel monoclonal antibody against human Tim‐3 (L3G) and investigated its roles in inhibiting Tim‐3 signalling and overcoming immune tolerance in T cells and monocytes/macrophages. The administration of L3G to cultured peripheral blood mononuclear cells (PBMCs) significantly increased the production of IFN‐γ and IL‐2 and the expression of type I interferon. The administration of L3G also increased the production of IFN‐γ, IL‐8 and type I interferon in U937 cells and primary monocytes. We investigated the mechanisms by which L3G enhances pro‐inflammatory cytokine expression, and our data show that L3G enhances STAT1 phosphorylation in both monocytes/macrophages and T cells. Finally, in an H1N1 infection model of PBMCs and U937 cells, L3G decreased the viral load and enhanced the expression of interferon. Thus, we developed a functional antibody with therapeutic potential against Tim‐3‐mediated infection tolerance.     

T cell epitopes of Per a 10 modulate local-systemic immune responses and airway inflammation by augmenting Th1 and T regulatory cell functions in murine model

Peptide immunotherapy (PIT) represents a safe and efficacious therapeutic modality for allergic diseases. Present study evaluates immunotherapeutic potential of T cell peptides of major cockroach allergen, Per a 10 in murine model of airway allergy. Treatment with peptides T-P8 and T-P10 demonstrated maximal resolution of pathophysiological features such as reduced recruitment of inflammatory cells to airways, lowered specific IgE, induction of IgG2a antibodies in serum, immune deviation towards Th1 cytokine milieu, suppression of Th2 cytokines in BALF and splenocyte culture supernatant and resolution of lung inflammation. A significant increase in CD4⁺Foxp3⁺ cells in spleen indicate towards induction of T regulatory cell mediated peripheral tolerance characterized by shift in cytokine milieu from Th2 to T regulatory cytokines. PIT modulates regulation of immune responses at both local and systemic levels, contributes towards holistic improvement in allergic features in mice and thus demonstrate potential for safe, specific and efficacious treatment for cockroach allergy.     

2018 ATC/TTS器官移植前沿热点回顾及进展概述

重点概述2018年美国移植大会及第27届国际移植大会有关器官移植基础、临床及转化医学研究的前沿热点及最新进展，包括供者特异性抗体、抗体介导排斥反应、临床免疫耐受、供器官合理利用、供肝保存新技术应用及移植相关病毒感染等概要内容。     

创新药吡非尼酮胶囊在中国健康人体耐受性和安全性研究

目的：评价中国健康受试者单次和多次口服1.1类创新药吡非尼酮胶囊后的人体耐受性和安全性。方法：依据动物实验结果推算起始和最大剂量，以健康受试者为研究对象，从安全起始剂量开始，进行单次和多次给药耐受性试验。采用随机单中心临床研究，统一餐后给药。单次给药耐受性试验：36例，随机分成6个剂量组：200 mg（2例），400 mg（4例），800 mg（6例），1 200 mg（8例），1 800 mg（8例），2 400 mg（8例）；多次给药耐受性试验：12例，分成2个剂量组：400 mg（6例），600 mg（6例），每天3次，连续给药7 d。观察受试者用药前后症状、生命体征、实验室检查变化（包括血尿常规、肝肾功能、心电图等）、并记录药品不良事件。结果：单次和多次给药耐受性试验的受试者用药前后生命体征和心电图无显著变化，实验室检查等表明无器质性损伤。依据试验终止标准，20例受试者完成4个剂量组的单次耐受性研究。其中单次给药耐受性试验有12例，多次给药耐受性试验有7例受试者在口服药物后出现轻中度恶心、呕吐、烧心、食欲不振、头晕和头痛等不良事件，未经处理自行缓解。本试验过程中未发生严重不良事件。结论：中国健康人体对吡非尼酮胶囊单次（200~1 200 mg）或多次（400~600 mg，tid×7 d）给药的安全性和耐受性良好，将为临床合理应用提供依据。     

Addressing risk management difficulties in children with food allergies

Risk is a concept inherent in every medical procedure. It can be defined as the probability of an adverse event in a defined population over a specified period of time. In the frame of food allergy management, it might be related to a diagnostic procedure, a treatment, or the consumption of foods. The risk of an adverse event can also be augmented by individual factors. This rostrum article discusses various aspects faced by children with food allergies in the light of risk, and their practical implications. Identifying personal risks for severe reaction, such as unstable asthma, and correcting them whenever possible also contribute to a reduction of the risk inherent to food allergy. Among the facets discussed, oral food challenges (OFC) are the most common diagnostic procedures implying an inherent risk. The risk of OFCs can be minimized by correct indication and timing of the test, a safe setting, as well as by ensuring that the patient is otherwise well without potential stressor potentially increasing the risk of a more severe reaction. Oral immunotherapy (OIT) has been studied as a potential treatment for increasing the threshold dose for reaction, and thus reducing the risk of accidental reaction. Nevertheless, the procedure is not devoid of risk as the patients may and do often react during the course of the procedure. Ingestion of trace amounts in processed foods, mainly in community settings such as restaurants, schools, or day care, represents a potential risk of reactions, although for a minority of patients. Precautionary allergen labeling (PAL) is a widespread strategy to reduce the potential risk of reactions due to traces. However, PAL is currently inefficient due to inconsistent labeling, also not indicating a clear maximum amount possibly present in the manufactured food. Finally, cost-effectiveness needs to be considered in risk management, as many risk reduction procedures are clearly not cost-effective.     

Interactions between human microbiome,liver diseases,and immunosuppression after liver transplant

In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.