神经精神性红斑狼疮的免疫学机制及其常用动物模型研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是以系统性、慢性、复发-缓解交替为特征的自身免疫性疾病典型代表,主要临床特点是血循环可检出大量自身抗体及多器官受损,其中神经精神性红斑狼疮(neuropsychiatric systemic lupus erythematosus,NPSLE)是常见并发症,患病率介于37%~95%之间,仅次于狼疮性肾炎,已成为影响SLE患者预后的主要因素之一[1]。目前NPSLE发病机制仍有很多未明之处,诊断与治疗仍面临很多挑战[2],加强NPSLE发病机制研究意义重大。本文将主要从神经免疫界面受损、免疫效应细胞、炎症因子、致病性自身抗体在NPSLE中发病作用研究进展及NPSLE研究常用动物模型进行综述,为阐明NPSLE发病机制和寻找研究靶点提供参考。     

系统性红斑狼疮发病机制相关MicroRNA的研究现状

MicroRNA(miRNA)是新发现的参与高等生物基因表达调控的重要分子,很多新的证据显示miRNA在免疫功能的调控方面占据着举足轻重的地位。系统性红斑狼疮(systemic lupus erythematosus,SLE)是自身免疫性疾病的原型,它以抗核抗体为代表的自身抗体的产生、免疫复合物沉积及多系统损害为特征。SLE的发病机制长期以来是风湿免疫研究领域的难点。本文综述目前所知的与系统性红斑狼疮发病机制相关的microRNA。     

Toll样受体7及9与系统性红斑狼疮的研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种病程反复、累及多种器官的自身免疫性疾病,其免疫学特征主要是高滴度的自身抗体和伴随抑制性T淋巴细胞减少的自身反应性B淋巴细胞增多,但机制尚未完全清楚.     

系统性红斑狼疮患者血清IL-18、IL-8水平观察

<正>系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种可累及多种系统、原因不明的自身免疫性疾病。临床表现为血清中出现多种自身抗体,常累及肾脏,引起狼疮性肾炎,最后导致患者死亡[1]。据报道70%的SLE患者有肾脏受损的表现,引发狼疮性肾炎(lupus nephritis,LN),严重者可导致肾功能衰竭[2]。细胞因子异常分泌在SLE发病中发挥着     

Pristane诱导狼疮鼠模型

系统性红斑狼疮(Systemic lupus erythematosus,SLE)是一种累及全身多系统器官组织的自身免疫性疾病,血清中存在以抗核抗体、抗dsDNA抗体为代表的多种自身抗体,目前病因、发病机理尚不完全清楚。合适的动物模型有助于对其进行研究。SLE动物模型分为自发性模型和诱导性模型。自发性狼     

老药新用在系统性红斑狼疮中的研究进展

系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种慢性自身免疫性疾病, 确切机制尚未完全阐明。治疗上除糖皮质激素、免疫抑制剂外, 生物制剂、小分子靶向药也逐步用于临床。虽然以上药物提高了疾病缓解率, 但仍有部分患者治疗效果不满意, 且因药物副作用或价格昂贵不能长期用药。近年来, 老药新用在SLE的治疗中发挥了重要作用。文章就目前研究较多的老药在SLE治疗中作用机制及安全性做一综述, 以期为SLE的发病机制及治疗提供新策略。     

系统性红斑狼疮患者血清25羟基维生素D_3水平与γ干扰素及白细胞介素6水平呈负相关

正系统性红斑狼疮(systemic lupus erythematosus,SLE)患者机体淋巴细胞功能失调,产生多种自身抗体,发病机制复杂[1]。维生素D属于类固醇激素,在血中主要形式是25羟基维生素D3[25(OH)VD3],在肾脏1α羟化酶作用下生成活性形式1,25二羟基维生素D3[1,25(OH)2VD3],1,25(OH)2VD3可通过淋巴细胞影响机体免疫系统[2-3]。由于25(OH)     

SLE患者外周血CD40-CD40L测定的临床意义

系统性红斑狼疮（systemic lupus erythematosus，SLE）是一种以自身抗体和免疫复合物产生为特征的结缔组织疾病。SLE的发病机制复杂，至今仍未完全阐明，现在普遍认为免疫调节异常在其发病中起到了主导作用，其中包括一对共刺激信号CIMO CIMOL的调节异常，淋巴细胞的功能失衡、异常活化等。本文采用流式细胞术测定SLE患者CIMO—CIMOL、异常活化淋巴细胞的表达，以及与疾病活动度的关系，为揭示SLE的发病机制提供实验依据。     

核酸识别Toll样受体特性及在系统性红斑狼疮中的作用

系统性红斑狼疮（systemic lupus erythematosus，SLE）是一种由于免疫系统紊乱导致机体产生多种自身抗体的自身免疫病。SLE发病缓慢，临床表现多样化，涉及多个系统和多种脏器损伤，造成细胞和体液免疫功能障碍，产生多种自身抗体。SLE的常见临床表现为发热、皮疹、关节痛、浆膜炎及肾、心血管、肺、神经系统、消化系统等系统损伤，死亡率高。虽然目前SLE发病的确切机制尚不清楚，但对于其发病原因比较公认的是核酸识别Toll样受体对于自身核酸复合物的识别而引发的针对自身的免疫反应。     

系统性红斑狼疮中T细胞作用的研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是多种因素相互作用引起的自身免疫性疾病,T细胞在其发生发展中发挥重要作用。近年来通过对SLE中T细胞的抗原特异性和克隆扩增特点的研究,发现SLE中T细胞识别特异性自身抗原,参与其发病的各个环节,并在SLE的病程持续中发挥重要作用。本文拟就有关内容作一综述。     

抗NMDA 受体抗体在神经精神狼疮发病机制中的研究进展

系统性红斑狼疮是一种累及全身多个器官和系统的自身免疫病,出现神经精神症状时,称为神经精神狼疮(NPSLE)。N-甲基-D-天(门)冬氨酸(NMDA)受体是一种跨膜离子通道型谷氨酸受体,抗NMDA 受体抗体主要分为抗NR1 型和抗NR2 型,近年抗NMDA 受体抗体在NPSLE 的发病机制中的作用成为一研究热点,尤其是抗NR2 抗体与NPSLE 密切相关,本文就到目前为止NMDA 抗体在NPSLE 中的作用机制的研究进展作一综述。     

Blood-brain barrier disruption and neuroinflammation as pathophysiological mechanisms of the diffuse manifestations of neuropsychiatric systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that can involve nervous system commitment known as neuropsychiatric systemic lupus erythematosus (NPSLE). The diagnostic of NPSLE is complex because the symptoms range from focal symptoms (e.g., strokes, thrombotic events) to diffuse disorders affecting cognition, mood and level of consciousness (e.g. acute confusional state, psychosis). Both type of manifestations of NPSLE differ in their pathological mechanisms. The focus of this review will be on the mechanisms that lead to the blood-brain barrier (BBB) disruption and to the neuroinflammation related with the diffuse manifestations of NPSLE.     

Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review

Diffusion tensor imaging (DTI) maps the brain's microstructure by measuring fractional anisotropy (FA) and mean diffusivity (MD). This systematic review describes brain diffusion tensor Magnetic resonance imaging (MRI) studies in systemic lupus erythematosus (SLE).The literature was reviewed following the PRISMA guidelines and using the terms “lupus”, “systemic lupus erythematosus”, “SLE”, “diffusion tensor imaging”, “DTI”, “white matter” (WM), “microstructural damage”, “tractography”, and “fractional anisotropy”; the search included articles published in English from January 2007 to April 2017. The subjects included in the study were selected according to the ACR criteria and included 195 SLE patients with neuropsychiatric manifestation (NPSLE), 299 without neuropsychiatric manifestation (non-NPSLE), and 423 healthy controls (HC). Most studies identified significantly reduced FA and increased MD values in several WM regions of both NPSLE and non-NPSLE patients compared to HC. Subclinical microstructural changes were observed in either regional areas or the entire brain in both the non-NPSLE and NPSLE groups.     

Psychiatric manifestations in systemic lupus erythematosus

Psychiatric abnormalities are common in systemic lupus erythematosus (SLE) with a prevalence of 17% to 75%, reflecting different methods of patient selection and assessment, the different professional orientation of clinicians, and lack of an accepted consensus for diagnosing active neuropsychiatric lupus (NPSLE). The psychiatric syndromes included in the ACR Neuropsychiatric Lupus Nomenclature Committee criteria are cognitive dysfunction, acute confusional state (delirium), anxiety disorder, mood disorder, and psychosis. In SLE patients, identification of psychiatric phenomena and the generation of a differential diagnosis are crucial. Possible mechanisms include vascular injury and pathogenic antibodies. Treatment strategies are based on small case studies. The purpose of this review is to discuss clinical manifestations, pathogenesis and the present therapeutic options in psychiatric lupus.     

Neuropsychiatric features of systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious and well known complication of systemic lupus erythematosus that remains a significant source of morbidity and mortality. Fortunately, advances in neuroimaging techniques and cognitive testing have improved the diagnosis of this disease and allowed earlier and more successful therapeutic intervention. Further, the association of NPSLE with the anti-phospholipid syndrome, other autoantibodies and inflammatory cytokines have also provided clues to the diagnosis and pathophysiology. Treatment of NPSLE is largely symptom based with outcome based on appropriate diagnosis.     

A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus

The discovery of autoantibodies to ribosomal proteins (anti-RibP) dates back more than fifty years when antibodies to ribosomes were identified in systemic lupus erythematosus (SLE) sera. Over the years, anti-RibP autoantibodies have been the subject of extensive study and became known as a highly specific biomarker for the diagnosis of SLE and were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN) and hepatitis (LH). As demonstrated by studies on cultured human cells and of murine models, there is evidence to suggest that anti-RibP may have a pathogenic role in LN and NPSLE. Despite a wealth of evidence, in comparison to other SLE autoantibodies such as anti-Sm and anti-dsDNA, anti-RibP has not been included in classification criteria for SLE. A significant challenge is the variability of assays used to detect anti-RibP, including the antigens and diagnostic platforms employed. This may account for the marked variation in frequencies (10–47%) in SLE and its association with clinical and demographic features reported in SLE cohorts. We performed a systematic literature review and meta-analysis to help clarify its prevalence, various clinical and serological associations in SLE based on the different RibP antigens and assay platforms used.     

抗 C1q 抗体及补体 C3、C4 在神经精神性狼疮诊断中的应用价值

目的:探讨抗C1q 抗体及补体C3、C4 在神经精神性狼疮诊断中的应用价值。方法:对22 例狼疮脑病及66例SLE 患者进行横断面研究。抗C1q 抗体采用ELISA 方法,C3 及C4 采用免疫比浊法检测。分析补体与狼疮脑病的临床表现相关性,采用Logistic 回归分析狼疮脑病的危险因素。结果:NPSLE 患者抗C1q 抗体水平明显高于非NPSLE 患者,补体C4明显低于非NPSLE 患者,采用ROC 曲线分析抗C1q 抗体诊断NPSLE 敏感性及特异性分别为63.6%、66.7%。单因素分析后发现抗C1q 抗体、抗核糖体P 蛋白抗体、抗核小体抗体与神经精神性狼疮相关,但多因素Logistic 回归分析并未发现其与狼疮脑病发生有关。补体C4 降低与SLE 患者脑血管意外发生有关。结论:抗C1q 抗体在狼疮脑病诊断中具有一定的诊断价值,且补体C4 可能参与狼疮脑病脑血管意外的发生。     

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Mouse models of autoimmunity, such as (NZB × NZW)F1, MRL/MpJ-Faslpr (MRL-lpr) and BXSB mice, spontaneously develop systemic lupus erythematosus (SLE)-like syndromes with heterogeneity and complexity that characterize human SLE. Despite their inherent limitations, such models have highly contributed to our current understanding of the pathogenesis of SLE as they provide powerful tools to approach the human disease at the genetic, cellular, molecular and environmental levels. They also allow novel treatment strategies to be evaluated in a complex integrated system, a favorable context knowing that very few murine models that adequately mimic human autoimmune diseases exist. As we move forward with more efficient medications to treat lupus patients, certain forms of the disease that requires to be better understood at the mechanistic level emerge. This is the case of neuropsychiatric (NP) events that affect 50–60% at SLE onset or within the first year after SLE diagnosis. Intense research performed at deciphering NP features in lupus mouse models has been undertaken. It is central to develop the first lead molecules aimed at specifically treating NPSLE. Here we discuss how mouse models, and most particularly MRL-lpr female mice, can be used for studying the pathogenesis of NPSLE in an animal setting, what are the NP symptoms that develop, and how they compare with human SLE, and, with a critical view, what are the neurobehavioral tests that are pertinent for evaluating the degree of altered functions and the progresses resulting from potentially active therapeutics.     

Serum S100B levels in patients with lupus erythematosus: preliminary observation.

S100B is an astrocytic calcium-binding protein which has been proposed as a biochemical marker of brain damage or dysfunction in acute and chronic diseases. We investigated whether serum S100B levels could be related to systemic lupus erythematosus (SLE) activity. Patients were grouped as having inactive SLE (ISLE), active SLE without central nervous system (CNS) involvement (ASLE), or active SLE with unequivocal neurologic or psychiatric manifestation (NPSLE). The control group consisted of age- and sex-matched healthy blood donors. S100B levels were determined using a luminescence immunoassay. All SLE groups had higher levels of serum S100B than the control group. Among the SLE groups, significantly higher levels of serum S100B protein were found in the NPSLE group than in the ISLE and ASLE groups, and there was no significant difference in S100B levels between the ISLE and ASLE groups. These preliminary results point to a putative relevance of serum S100B protein levels in SLE patients, specifically concerning CNS involvement present in this disease.