抗核抗体谱在96例自身免疫病中的应用探讨

多数自身免疫疾病患者血清中会出现自身抗体,这些自身抗体在自身免疫病的诊断和疗效评价等方面具有重要意义。检出一种自身抗体涉及多种相关自身免疫病,一种自身免疫病可检测出多种自身抗体,因此临床往往参考多种免疫指标作出诊断。我们应用欧蒙印迹法技术检测分析96例自身免疫病患者的抗核抗体谱,对其在临床诊断与应用进行探讨。1材料与方法1.1标本来源:自身免疫病患者血清96份,均来自本院门诊及住院病人,其中SLE(系统性红斑狼疮)9例,MCTD(混合性结缔组织病)14例,PSS(硬皮病)7例,SS(干燥综合征)7例,PM/DM(多发性肌炎/皮肤炎)11例,R…     

甲巯咪唑导致胰岛素自身免疫综合征诊治分析

目的 探讨甲巯咪唑导致胰岛素自身免疫综合征及时有效的诊断思路和治疗策略。方法 对河南省人民医院应用甲巯咪唑治疗Graves病导致胰岛素自身免疫综合征的病例资料进行回顾性分析。结果 2例患者均为应用甲巯咪唑治疗Graves病过程中出现自发性低血糖发作,血胰岛素水平升高及胰岛素自身抗体阳性,停用甲巯咪唑后低血糖逐渐缓解,胰岛素自身抗体转为阴性。结论 甲巯咪唑治疗Graves病时可诱发胰岛素自身免疫综合征,检测胰岛素自身抗体有助于诊断,预后良好,但需要加强对其的认识,及早做出诊断,及早治疗,避免漏诊、误诊。     

济南地区946例抗核抗体检测结果的临床分析

目的探讨济南地区临床就诊患者自身抗体的阳性分布情况及在自身免疫病中的临床意义。方法采集济南军区总医院检测自身抗体标本946例。采用间接免疫荧光法(IIF)对抗核抗体(ANA)进行初筛试验,再采用免疫线性印迹法(LIA)检测抗核抗体谱(ANAs)进行确证试验。结果女性自身抗体的阳性率比男性高;ANA核型以核颗粒型、核均质型、胞质颗粒型及着丝点型较多;ANAs结果中以抗Ro-52抗体、抗SS-A抗体、抗SS-B抗体、ACA、AMA-M2较多。结论女性自身免疫病发病率较高。ANA与ANAs的联合检测可为自身免疫病的诊疗提供更全面的依据。     

抗CD22单克隆抗体治疗自身免疫病研究进展

CD22是特异性表达于B淋巴细胞上的Ⅰ型跨膜糖蛋白，属于免疫球蛋白超家族中唾液酸黏附素家族成员，其作为抑制性辅助受体在B细胞的调节与体液免疫中发挥重要作用。自身免疫病是由自身免疫失调所致，B细胞异常激活以及致病性自身抗体的生成是自身免疫病的重要特征之一。通过抗CD22单克隆抗体治疗B细胞异常增殖活化介导为主的自身免疫病，如系统性红斑狼疮和类风湿性关节炎等，已引起关注。此文就CD22的分子特征、功能以及靶向CD22治疗自身免疫相关性疾病的研究进展进行综述。     

彩色多普勒血流显像在甲状腺机能亢进诊断中的应用

甲状腺功能亢进是一种伴甲状腺激素分泌增多的器官特异性自身免疫病。近代研究证明：甲状腺功能亢进是在遗传的基础上,因感染、精神创伤等因素应激而诱发,属于抑制性T淋巴细胞功能缺陷所致的一种器官特异性自身免疫病。其可能与自身TSH受体抗体、抑制性T淋巴细胞功能缺陷、     

新型冠状病毒感染相关的神经系统表现

新型冠状病毒(SARS-CoV-2)是一种新型的冠状病毒，是导致SARS-CoV-2感染疫情暴发的原因。目前，SARS-CoV-2感染疫情的大流行已成为一个具有挑战性的世界问题。尽管大多数SARS-CoV-2感染患者主要出现呼吸道症状，但观察到与SARS-CoV-2感染相关的神经系统症状和表现越来越多。该文详细阐述了相关文献报道的SARS-CoV-2感染的嗜神经机制和神经系统症状及表现，包括味觉和嗅觉功能障碍、肌肉疼痛、头痛、精神状态改变、意识模糊、谵妄和头晕。回顾了SARS-CoV-2感染相关的神经系统症状及其可能的发生机制，希望有助于后续的相关研究和临床诊治。     

系统性红斑狼疮与外周血T细胞亚型的相关性研究

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种多因素参与的特异性的自身免疫病，患者突出表现为有多种自身抗体(最主要的是抗双链DNA抗体)，并通过免疫复合物等途径，造成几乎周身每一系统、每一器官都可能受累。1986年Mosmann首次提出CD4^ 细胞分化为两群。即Th1．Th2，其中Th1分泌白细胞介素(IL)-2、干扰素(IFN)-1、肿     

常用自身抗体测定法的临床价值

自身抗体(AAb)是诊断自身免疫病的必要条件,但并非有AAb即自身免疫病。Roitt(1980)根据病变范围,AAb性状,将自身免疫病分为(1)有器官特异性AAb的器官特异性疾病;(2)AAb为器官非特异性的,但病变有局限于单一脏器的倾向;(3)有器官非特异性AAb的全身性疾病(见表1)。本文着重介绍以下几种常用的AAb测定方法(抗核抗体已在前文介绍)。     

新型冠状病毒治疗靶点及药物研究进展

目的探索SARS-CoV-2的治疗靶点,治疗药物和疫苗研发的近况,为其后期的研究提供思路。方法通过检索国内外的专业数据库,对SARS-CoV-2的最新文献进行解读,获取相关数据。结果目前研究出2个抗病毒药物靶点,一个抗体和疫苗的靶点及一个开发检测试剂的靶点,可能的有效药物和疫苗也已经开始临床研究。结论目前SARS-CoV-2的针对性靶点已清楚,候选药物和疫苗的疗效尚待确认。     

多种自身抗体联合检测对自身免疫性疾病临床诊断的意义

目的探讨多种自身抗体联合检测在自身免疫病中的临床意义。方法对100例自身免疫性疾病患者的实验室及临床资料进行回顾性分析。结果抗ds-DNA、抗Sm、Po与系统性红斑狼疮(SLE)相关,抗Histones与多种结缔组织病相关,抗U1-RNP与混合性结缔组织病(MCTD)、类风湿性关节炎(RA)、硬皮病、干燥综合征相关,CENP-B与局限型系统性硬化、RA、SLE、原发性干燥综合征相关,抗SS-A、抗SS-B与干燥综合征及SLE相关,Scl-70与系统性硬化相关,Jo与多发性肌炎相关。结论自身抗体的实验室检测对自身免疫疾病的诊断有重要意义。     

新型冠状病毒感染相关儿童多系统炎症综合征与细胞因子风暴

儿童多系统炎症综合征（MIS-C）是一种合并多器官功能受损的全身炎症综合征,大多数患儿存在新型冠状病毒（SARS-CoV-2）感染证据或新型冠状病毒肺炎（COVID-19）患者接触史。患儿常出现发热、胃肠道症状、心功能异常及休克等表现。细胞因子风暴（CS）是由外界刺激触发的全身性炎症反应,引起CS的诱因包括医源性、病源性、单基因或自身免疫性疾病等。MIS-C发病机制尚未完全明确,可能与SARS-CoV-2感染后引起的机体过度免疫反应有关。就COVID-19感染相关MIS-C的临床特征和CS的发生及诱因予以综述,并讨论两者间的关系,以期为MIS-C的机制研究和临床诊断提供参考。     

134例自身免疫性肝病患者自身抗体的分析

目的：探讨自身免疫性肝脏疾病的自身抗体特征，以提高对该病的认识。方法：在134例患者中,原发性胆汁性肝硬化（PBC）73例，自身免疫性肝炎（AIH）43例，原发性硬化性胆管炎（PSC）4例，乙型病毒性肝炎（HBV）3例，丙型病毒性肝炎（HCV）6例，非甲-戊型病毒肝炎（Non A-E）5例。采用间接免疫荧光法、免疫印迹法等分别检测抗核抗体（ANA）、抗线粒体抗体（AMA）、抗肝肾微粒体抗体Ⅰ型（LKM-1）、抗可溶性肝抗原，肝胰抗原（SLA／LP）和AMA-M2亚型等。结果：6例LKM-1阳性，6例SLA／LP阳性，分别见于AIH、AIH／PBC重叠综合征和HCV患者。PBC患者AMA和AMA-M2阳性率为94．5％，ANA阳性率为90.4％，以胞浆型为主（32／66）。AIH患者的ANA阳性率为90．7％，以核膜型为主（19／39）。非甲～戊组，2例AMA和AMA—M2阳性，1例SMA阳性。结论：检测自身抗体有助于该病的诊断，临床不能忽视肝功能异常的患者，诊断时应考虑可能患有自身免疫性肝病。     

Enzymes as target antigens of liver-specific autoimmunity: the case of cytochromes P450s

Characterization of liver-specific autoantigens has given a fresh impetus to research in the pathogenesis of autoimmune liver diseases, viral-triggered and drug-induced autoimmunity affecting the liver. Intriguing is the fact that most of the liver-specific autoantigens are enzymes of key importance for cell's homeostasis. Detection of autoantibodies against the respective antigens is carried out for diagnostic and research purposes using indirect immunofluorescence, immunoblotting, enzyme-linked immunosorbent assays, radioimmunoassay, immunoprecipitation or assays determining inhibition of enzyme activity. In patients with autoimmune hepatitis, a liver disorder of unknown etiology and pathogenesis, disease-specific autoantibodies are frequently directed against drug metabolizing enzymes of phase 1, namely cytochrome P450 2D6 (CYP2D6). The same and other members of these families of enzymes (CYPs) have also been described as targets of liver-specific autoimmunity in chronic hepatitis C virus (HCV)-infected patients, patients with autoimmune hepatitis as part of the autoimmune polyglandular syndrome type-1 (APS-1) and drug-induced autoimmunity. How these enzymes become 'self targets' is not yet established. An antigen release following hepatocyte injury could provide the stimulus for an immune response towards epitopes on these enzymes but the highly-specific, antigen-restricted initiation of the observed autoimmune response is against such an explanation. Accordingly, in this review we will focus on the pathogenic role -if any- of autoimmune responses against liver-related CYPs in autoimmune hepatitis, HCV infection, APS-1 and drug-induced autoimmunity. Learning more about the specificity of antibody responses against these enzymes may help us better understand the mechanisms underlying liver autoimmunity and may facilitate the development of therapeutic and preventive interventions.     

Immunogenicity,breakthrough infection,and underlying disease flare after SARS-CoV-2 vaccination among individuals with systemic autoimmune rheumatic diseases

Many patients with systemic autoimmune rheumatic diseases (SARDs) require immunosuppression to reduce disease activity, but this also has important possible detrimental impacts on immune responses following vaccination. The phase III clinical trials for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines did not include those who are immunosuppressed. Fortunately, we now have a clearer idea of how immune responses following SARS-CoV-2 vaccination has for the immunosuppressed, with much of the data being within a year of its introduction. Here, we summarize what is known in this rapidly evolving field about the impact immunosuppression has on humoral immunogenicity including waning immunity and additional doses, breakthrough infection rates and severity, disease flare rates, along with additional considerations and remaining unanswered questions.     

Antibodies as predictors of complex autoimmune diseases and cancer

The pathologic role of autoantibodies in many autoimmune diseases is widely accepted. An enzyme immunoassay was used for measurement of antibodies against disease-specific antigens and etiologic agents for cross-reactive antigens associated with them. This antibody assay was applied to a panel of antigens for the detection of different neuroautoimmune diseases that included multiple sclerosis, motor peripheral neuropathies, multifocal motor neuropathy, amyotrophic lateral sclerosis, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. We studied women with pregnancies complicated by neural tube defect, neuroborreliosis, autism and patients with possible somatic hypermutation. Antibodies were also measured against antigens and etiologic agents associated with primary biliary cirrhosis and chronic obstructive pulmonary disease. And, finally, antibodies were measured against several tumor antigens or peptides which are expressed in prostatic, breast and colon tissues. This panel of different autoantibodies was applied to 290 patients with neuroautoimmune disorders, cancer, and possible somatic hypermutation. The levels of these antibodies against different tissue-specific antigens and etiologic agents associated with them were significantly elevated in patients versus controls. We hope that this novel 96 antigen-specific ELISA will be used in additional studies that will prove its clinical efficacy, not only for the early diagnosis of many neuroautoimmune, liver and lung autoimmune disorders, but also for prognosis and the implementation of preventive steps for many complex diseases.     

肝病相关自身抗体检测在自身免疫性肝病诊断中的价值研究

目的 自身免疫性肝病临床流行病学调查,观察各肝病患者中自身抗体检测的阳性率,自身免疫性肝病检测的阳性率;探讨自身抗体检测对自身免疫性肝病的诊断价值.方法 对2007年10月至2010年10月2 714份自身抗体检验结果进行回顾性分析,并对自身抗体阳性病例的查阅临床资料.结果 2 714份血清中自身抗体阳性472例,阳性率17.4％,抗核抗体(ANA)阳性418例,阳性率15.4％,抗线粒体抗体(AMA)阳性124例,阳性率4.57％,抗平滑肌抗体阳性91例,阳性率3.35％,抗肝肾微粒体抗体( LKM)阳性16例,阳性率0.59％,抗肝细胞膜抗体阳性(LMA)8例,阳性率0.29％,抗肝细胞溶质抗原1型抗体(LC-1)阳性5例,阳性率0.18％,抗肝特异性脂蛋白抗体(LSP)阳性3例,阳性率0.11％,2 914例送检标本中诊断为AIH 59例,阳性率为2.17％,诊断为PBC 61例,阳性率为2.24％.自身抗体阳性患者74.57％诊断为病毒性肝炎及相关疾病.结论 自身抗体检测是诊断自身免疫性肝病的必要条件,但这些自身抗体也可见病毒性肝炎,药物性肝炎及其他疾病.     

Sex hormones as immunomodulators in health and disease.

In addition to their effects on sexual differentiation and reproduction, sex hormones influence the immune system. This results in a gender dimorphism in the immune function with females having higher immunoglobulin levels and mounting stronger immune responses following immunization or infection than males. The greater immune responsiveness in females is also evident in their increased susceptibility to autoimmune diseases. However, a clear understanding of the myriad of effects that sex hormones have on the immune system is lacking. Studies in normal mice show that estrogen treatment induces polyclonal B cell activation with increased expression of autoantibodies characteristic of autoimmune diseases. Several mechanisms appear to contribute to the break in tolerance and the increase in plasma cell activity including a reduction of the mass of the bone marrow and the thymus, the emergence of sites of extramedullary hematopoiesis and altered susceptibility of B cells to cell death. In addition, sex hormone levels in both humans and experimental models correlated with the activity of their cytokine-secreting cells indicating that sex hormones influence the cytokine milieu and suggesting that altered sex hormonal levels in autoimmune patients contribute to the skewed cytokine milieu characteristic of systemic lupus erythematosus (SLE). While sex hormones alone do not cause autoimmune disease, abnormal hormone levels may provide the stage for other factors (genetic, infectious) to trigger disease. Understanding the physiology of the interaction between sex hormones and immune function and its potential pathological consequences may provide insight into the autoimmune diseases and new directions for their treatment.     

118例病原学指标阴性的肝病患者病因临床分析

目的了解肝炎病毒血清学标志阴性的肝病患者的病因。方法选择甲、乙、丙、丁、戊型病毒性肝炎血清学标志阴性的患者118例。对临床上诊断为病原学阴性的肝病患者血清,分别进行自身免疫性肝病抗体,ANA全套,FT3、VF4及TSH,血清Cu及铜蓝蛋白的检测。收集临床资料,分析结果。结果118例肝炎病毒血清学标志阴性的肝病患者中47例是病因不明的肝病,在病因不明的47例肝病患者中,14例患者的血清ANA等自身抗体中至少一种抗体为阳性。结论对病因不明的肝病有必要检测自身抗体,以排除自身免疫性肝病。     

Relationship of Anti-vimentin antibodies to anti-endothelial antibodies

The intermediate filament protein vimentin is a potential target antigen for autoantibodies in some infectious and autoimmune diseases. Because endothelial cells contain an extensive interconnecting cytoplasmic network of vimentin, we examined the relationship between anti-vimentin and anti-endothelial cell antibodies (AECAs). We measured the level of anti-vimentin antibodies in patients with systemic autoimmune diseases (n=42), healthy blood donors (n=58), and patients with acute inflammation and showing anti-vimentin immunofluorescence (n=50). AECAs were detected by indirect immunofluorescence in human umbilical vein endothelial cells. Anti-vimentin antibodies were detected by indirect immunofluorescence in HEp-2 cells, and levels of anti-vimentin antibodies were measured using an enzyme-linked immunosorbent assay. We did not find significant differences in anti-vimentin levels between AECA-positive and-negative samples for any of the groups; however, serum anti-vimentin antibody levels were significantly higher in patients with acute non-autoimmune inflammatory diseases than in patients with systemic autoimmune diseases or healthy controls. There were no differences between the levels of anti-vimentin antibodies between patients with systemic autoimmune diseases and healthy individuals. The anti-vimentin antibodies levels also did not correlate with the AECA positivity.     

Optimized synthesis,polymer conjugation,and proof-of-concept studies of the gd-IgA1 epitope for antibody-scavenging therapies in IgA nephropathy

IgA nephropathy (IgAN) is the most common glomerular autoimmune disease and has severe long-term consequences for patients, with 40% of the patients eventually progressing to end-stage renal disease. Despite the severity, no causal treatment is currently available. While the pathogenesis of IgAN is complex, disease severity is linked to autoantibodies against the gd-IgA1 epitope, a stretch in the hinge region of IgA1 that lacks O-glycans and is found in the characteristic immune complexes deposited in the kidneys of IgAN patients. One elegant, causal approach would be to remove the anti-gd-IgA1 autoantibodies and consequently reduce the immune complex burden on the kidneys. The administration of synthetic polymers that present autoantigens in a multivalent manner have been established as promising therapeutic strategies in other autoimmune diseases and may be applied to IgAN. We here present an improved protocol for the synthesis of the gd-IgA1 epitope, its successful coupling to a poly-L-lysine polymer and proof-of-concept experiments that the polymer-bound synthetic glycopeptide is able to capture the IgAN autoantibodies, making this approach a promising way forward for developing a targeted treatment option for IgAN patients.