微柱凝集技术检测直接抗人球蛋白试验结果分析

目的 分析进行直接抗人球蛋白试验(DAT)患者的检测结果,了解DAT阳性结果疾病的分布情况.方法 收集65例DAT阳性结果患者的临床资料,回顾性分析其疾病与检测结果的关系.结果 临床诊断“贫血原因待查”患者DAT阳性率最高,占所有阳性患者的49.2％(32/65),其他DAT阳性患者的疾病基本符合文献报道.结论 血清DAT检查虽然不能确定患者是否有溶血性贫血,但是可以帮助鉴定溶血是否有免疫基础,从而有利于临床治疗以及选择适宜的时间输注适宜的血液成分.     

原发性胆汁性肝硬化免疫发病机制的研究进展

原发性胆汁性肝硬化(PBC)是一种自身免疫性疾病,以肝内胆管进行性破坏、慢性胆汁淤积为主要特征。PBC的发病机制复杂,涉及遗传易感性、免疫机制、感染因素及化学物质等。了解PBC的发病机制对于采取正确合理的治疗方案,降低其发病率和病死率意义重大。其中免疫机制与机体产生的自身抗体及免疫细胞分泌的多种细胞因子相关。本文就免疫因素在PBC发病机制中的作用进行综述。     

Clinical Relevance of Autoantibody Detection in Lung Cancer

Sensitive techniques have recently been developed to identify tumoral antigens and to detect tumor-related autoantibodies in the peripheral blood of patients with cancer. Studies of these new methods indicate that the detection of a combination of autoantibodies could be a relevant prescreening strategy for the early detection of lung cancer in patients at high risk. Nevertheless, the clinical utility of autoantibodies for determining prognosis and monitoring response to systemic therapies in lung cancer is less conclusive. This article summarizes the clinical background and the technical aspects of current methods used for the detection and characterization of autoantibodies in blood, with a special focus on the implications of these methods for the clinical management of patients with lung cancer.     

Are There Enhanced MBP Autoantibodies in Autism?

Autoantibodies to central nervous system antigens, such as myelin basic protein (MBP), may play a role in autism. We measured autoantibody titers to MBP in children with autism, both classic onset and regressive onset forms, controls (healthy age- and gender-matched) and individuals with Tourette syndrome via enzyme-linked immunosorbent assays. We found a significant difference in autoantibody titers to MBP, not accounted for by age or medication, between Tourette and classic autism (both significantly lower) when compared to regressive autism, but not when compared to controls. Autoantibody responses against MBP are unlikely to play a pathogenic role in autism.     

抗角蛋白自身抗体对培养角朊细胞产生白细胞介素8的影响

为探讨抗角蛋白自身抗体（AKantoAb）对角朊细胞免疫功能的影响，实验以IL-1β刺激无血清培养角朊细胞及AKautoAb作用后的角朊细胞，用夹心ELISA法检测培养上清中IL－8的产量。结果表明IL-1β可刺激角朊细胞产生IL－8，并对IL－1β有浓度依赖性，AKautoAb对角朊细胞产生IL－8有明显抑制作用。提示AKautoAb在炎性皮损角朊细胞中的沉着，可能存在有益的调节作用。     

Diego and Giorgina Vergani: The two hearts of translational autoimmunity

Since the publication of the first textbook on autoimmune diseases in 1963, the knowledge in the field has exponentially grown into numerous tracks of research, particularly at benchside. Systemic and organ-specific autoimmune diseases, as in the case of the liver, have witnessed notable advances in terms of epidemiology, genetics, effector and regulatory mechanisms, and ultimately treatment. While the available tools for communication have provided accelerating progress rates, we recognize that key opinion leaders continue to provide significant contributions to the field. The present issue is dedicated to celebrate Giorgina Mieli-Vergani and Diego Vergani as two of the finest examples of excellence in autoimmune liver diseases and the broader field of autoimmunity. Diego and Giorgina are extremely well-liked Colleagues who fully represent the translational efforts between laboratory research and clinically relevant questions in the practice of pediatric liver diseases and autoimmune hepatitis.     

Carbohydrate recognition systems in autoimmunity

The immune system is a complex functional network of diverse cells and soluble molecules orchestrating innate and adaptive immunity. Biological information, to run these intricate interactions, is not only stored in protein sequences but also in the structure of the glycan part of the glycoconjugates. The spatially accessible carbohydrate structures that contribute to the cell's glycome are decoded by versatile recognition systems in order to maintain the immune homeostasis of an organism. Microbial carbohydrate structures are recognized by pathogen associated molecular pattern (PAMP) receptors of innate immunity including C-type lectins such as MBL, the tandem-repeat-type macrophage mannose receptor, DC-SIGN or dectin-1 of dendritic cells, certain TLRS or the TCR of NKT cells. Natural autoantibodies, a long known effector branch of this network-based operation, are effective to home in on non-self and self-glycosylation also. The recirculating pool of mammalian immune cells is recruited to inflammatory sites by a reaction pathway involving the self-carbohydrate-binding selectins as initial recognition step. Galectins, further key sensors reading the high-density sugar code, exert regulatory functions on activated T cells, among other activities. Autoimmune diseases are being associated with defined changes of glycosylation. This correlation deserves to be thoroughly studied on the levels of structural mimicry and dysregulation as well as effector molecules to devise innovative anti-inflammatory strategies. This review briefly summarizes data on sensor systems for carbohydrate epitopes and implications for autoimmunity.     

Low prevalence of autoantibodies to CENP-H, -I, -K, -L, -M, -N, -T and -U in a Japanese cohort of anti-centromere positive samples

Objective: The constituents of the centromere region, centromere protein (CENP)-A, -B, and -C, are mainly targeted by anticentromere antibodies (ACA). Many other proteins also assemble around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). CENP-H, -I, -K, -L, -M, -N, -T, and -U have been reported as the constitutive components of ICEN. In this study, we examined the reactivities of ACA to the 8 CENPs for the purpose of investigating their autoantigenicity.

Methods: Sera from 95 patients with ACA were tested by western blotting (WB) and enzyme-linked immunosorbent assay (ELISA) with the recombinant C-terminal of CENP-B (Ct-CENP-B). Next, the sera were examined for autoantibodies against the 8 CENPs by WB with each recombinant protein. Furthermore, the coiled-coil motifs and granzyme B (GB) cleavage for various CENPs were analyzed with computer tools.

Results: Out of 95 ACA-positive sera, 85 and 93 sera were positive for anti-Ct-CENP-B antibodies in WB and in ELISA, respectively. In WB using the 8 CENPs, no sera reacted to any other 7 CENPs, except 1 serum, which reacted weakly to CENP-T. We were unable to find any obvious relationships between the autoantigenicity of CENPs and coiled-coil-forming probabilities or potential substrates for GB.

Conclusion: This study demonstrates that ACA rarely target the 8 CENPs, in contrast to CENP-B. Protein structures might not contribute in a major way to the autoantigenicity of CENPs.     

Antiphospholipid antibodies internalised by human syncytiotrophoblast cause aberrant cell death and the release of necrotic trophoblast debris

Antiphospholipid antibodies (aPL) are the strongest maternal risk factor for pre-eclampsia, a hypertensive disease of human pregnancy. Pre-eclampsia is triggered by a toxic factor released from the placenta that activates the maternal endothelium. Antiphospholipid antibodies cause the release of necrotic trophoblast debris from the placental syncytiotrophoblast and this debris can activate endothelial cells. In this study, we investigated how aPL affects syncytiotrophoblast death and production of necrotic trophoblast debris by examining the interaction between aPL and human first trimester placental explants. Human polyclonal and murine monoclonal aPL, but not control antibodies, were rapidly internalised by the syncytiotrophoblast. Inhibitors of endocytosis or the low-density lipoprotein receptor (LDLR) family, but not toll-like receptors, decreased the internalisation of aPL and prevented the release of necrotic trophoblast debris from the syncytiotrophoblast. Once internalised, aPL increased inner mitochondrial membrane leak and Cytochrome c release while depressing oxidative flux through Complex IV of the electron transport system in syncytiotrophoblast mitochondria. These data suggest that the human syncytiotrophoblast internalises aPL by antigen-dependent endocytosis involving LDLR family members. Once internalised by the syncytiotrophoblast, aPL affects the death-regulating mitochondria, causing extrusion of necrotic trophoblast debris which can activate maternal endothelial cells thereby contributing to the pathogenesis of pre-eclampsia.     

Lupus-prone B6.Nba2 male and female mice display anti-DWEYS reactivity and a neuropsychiatric phenotype

ObjectiveNeuropsychiatric lupus (NPSLE), a manifestation of the autoimmune disease systemic lupus erythematosus (SLE), is characterized by psychiatric symptoms including anxiety and depression and upregulated autoantibodies. The B6.Nba2 spontaneous mouse model develops SLE, but has not previously been tested for NPSLE.MethodsWe investigated the NPSLE phenotype in male and female B6.Nba2 mice (n = 12 each) and age- and sex-matched B6 controls (n = 10 each) via behavioral assessments for anxiety, depression, and memory deficits. Serum anti-dsDNA, anti-nRNP, anti-DWEYS peptide reactive IgG autoantibody levels and soluble TWEAK levels were determined by ELISA. Hippocampal regions were stained for activated microglia and neurons.ResultsBoth male and female B6.Nba2 mice showed elevated anti-dsDNA IgG, anti-nRNP IgG and anti-DWEYS reactive antibodies, elevated serum soluble TWEAK levels, and a strong anxiety and depression phenotype (p < 0.05–0.0001). Male B6.Nba2 mice developed this phenotype at a slightly older age than females. Female B6.Nba2 mice displayed reduced numbers of neurons in the hippocampal region compared to female B6 controls (p < 0.05).ConclusionThe B6.Nba2 mouse model recapitulates many known NPSLE phenotypes, making it a promising model to investigate the development of NPSLE in the context of SLE.