抗核抗体与抗ENA抗体的相关性分析

目的 探讨抗核抗体(ANA)荧光核型与抗可提取性核抗原(ENA)抗体不同项目阳性结果 之间的相关性.方法 抗核抗体采用间接免疫荧光法检测,抗ENA抗体采用欧蒙免疫斑点法检测.采用双肓对照法对比分析243例抗ENA抗体(抗nRNP/Sm、Sm、SS-A、SS-B、Scl-70和Jo-1抗体)阳性的病例ANA的荧光核型.结果 243例抗ENA抗体阳性的病例,ANA的阳性率为91.8%.主要以核浆颗粒型(包括细、粗颗粒)为主,约为51.0%(124/243),抗SS-A单独阳性时核型比较分散,核浆细颗粒型占28.3%(36/127).核浆粗颗粒型占19.7%(25/127).抗nRNP/Sm单独阳性时以核浆粗颗粒型为主,阳性率为56.3%(18/32).另外,350例ANA阳性病例中抗ENA抗体常规6项阳性率为63.7%(223/350).结论 抗ENA抗体阳性时并非都与ANA核浆颗粒型有关,抗核抗体(ANA)荧光核型与抗可提取性核抗原(ENA)抗体类型没有绝对的规律可言.随着对自身抗体的深入研究.目前抗ENA抗体谱的检测项目还有待进一步扩展.     

自身免疫性疾病中抗核抗体与抗ENA抗体的相关性分析

目的探讨抗核抗体(ANA)荧光核型与抗可提取性核抗原抗体(ENA)之间的相关性。方法 ANA采用间接免疫荧光法检测,抗ENA抗体采用德国欧蒙公司免疫斑点法检测,检测结果采用双盲对照法分析。结果 132例抗ENA抗体阳性病例ANA的阳性率为93.9%,荧光核型主要以颗粒型为主。另外检测的103例ANA阳性病例中,抗ENA抗体常规6项阳性率为78.6%。结论抗ENA抗体类型与ANA荧光核型之间没有绝对的规律,临床检测自身抗体时需将两者结合分析。     

抗核抗体与抗ENA抗体的相关性分析

目的探讨抗核抗体（ANA）荧光核型与抗可提取性核抗原（ENA）抗体不同项目阳性结果之间的相关性。方法抗核抗体采用间接免疫荧光法检测．抗ENA抗体采用欧蒙免疫斑点法检测。采用双肓对照法对比分析243例抗ENA抗体（抗nRNP／Sm、Sm、SS—A、SS—B、Scl-70和Jo-1抗体）阳性的病例ANA的荧光核型。结果243例抗ENA抗体阳性的病例,ANA的阳性率为91．8％。主要以核浆颗粒型（包括细、粗颗粒）为主。约为51．0％（124／243）,抗SS—A单独阳性时核型比较分散,核浆细颗粒型占28．3％（36／127）,核浆粗颗粒型占19．7％（25／127）。抗nRNP／Sm单独阳性时以核浆粗颗粒型为主,阳性率为56．3％（18／32）。另外．350例ANA阳性病例中抗ENA抗体常规6项阳性率为63．7％（223／350）。结论抗ENA抗体阳性时并非都与ANA核浆颗粒型有关,抗核抗体（ANA）荧光核型与抗可提取挂核抗原（ENA）抗体类型没有绝对的规律可言。随着对自身抗体的深入研究．目前抗ENA抗体谱的检测项目还有待进一步扩展。     

979例自身免疫性疾病抗核抗体与抗ENA抗体联合检测的结果分析

目的回顾本实验室开展抗核抗体(antinuclear antibody,ANA)与抗可提取性核抗原(extractable nuclear antigens,ENA)抗体联合检测的情况,分析两者之间的相关性,并探讨联合检测在自身免疫性疾病中的应用价值。方法间接免疫荧光法检测ANA,生物芯片技术检测抗ENA(ds-DNA、Sm、SS-A/Ro、SS-B/La、u1RNP、Scl-70、Jo-1、RibosomalP)抗体,并采用双盲法分析ANA阳性标本的荧光核型与抗ENA抗体的关系。结果979例临床标本中,ANA阳性的标本数为400例,阳性率为40.9%(400/979)。荧光核型主要是核颗粒型(249例)、核均质型(83例)、胞浆颗粒型(30例),同时对979例标本进行抗ENA抗体的检测,阳性标本数为199例,阳性率为20.3%(199/979),只有1例阳性出现在ANA阴性的标本中。在400例ANA阳性的标本中,抗ENA抗体的阳性率为49.5%(198/400),出现较多的阳性抗体是抗SS-A/Ro(133例)、抗RibP(78例)、抗u1RNP(70例)、抗ds-DNA(61例)、抗SS-B/La(40例)等抗体,主要与颗粒型荧光相关。而均质型ANA标本中,常见的抗ENA抗体是抗ds-DNA(37例)、抗SS-A/Ro(27例)、抗Jo-1(20例)、抗RibP(20例)等抗体。结论不同荧光核型的ANA与抗ENA抗体之间的关系有各自的特点。用间接荧光法筛查ANA,并联合抗ENA抗体谱进行分型,可以确定部分ANA靶抗原的类型,进一步扩展抗ENA抗体谱,才能准确确定靶抗原。     

818例自身免疫病抗ENA抗体与抗核抗体的对照分析

目的比较抗核抗体(ANA)荧光核型与抗可提取性核抗原(ENA)抗体结果之间的相互关系。方法ANA采用间接免疫荧光法检测,抗ENA抗体采用免疫印迹和免疫双扩散法检测,检测结果采用双盲对照比较分析。结果818例抗ENA抗体阳性中ANA的总阳性率97.4%,但有6.4%(8/125)针对分子量60000的SSA抗体和30.0%(3/10)抗Jo-1抗体阳性的标本ANA阴性。抗ENA抗体中抗Sm、U1-RNP抗体阳性时有94.4%(51/54)显示为ANA单纯的斑点型或合并有其他核型;抗SS-A、SS-B抗体阳性时核型较分散,斑点型占75.4%(49/65);抗Scl-70抗体阳性时以核仁型为主,阳性率为68.6%。82例斑点型ANA阳性病例中抗ENA抗体常规6项阳性率为67.1%(55/82)。结论ANA目前作为风湿免疫病的筛查实验还有欠缺,宜与抗ENA抗体同时检测。抗ENA抗体阳性时并非都与ANA斑点核型有关,需具体分析;ANA斑点型阳性时,抗ENA抗体常规项目可以为阴性,可扩大抗ENA抗体的检测范围。     

新疆石河子地区汉族人群ANA与抗ENA抗体的检测结果分析

目的回顾本实验室开展抗核抗体（antinuclear antibody,ANA）与抗可提取性核抗原（extractable nuclear anti-gens,ENA）抗体联合检测的情况,分析新疆石河子地区汉族人群中ANA与抗ENA抗体之间的相关性。方法间接免疫荧光法检测ANA,欧蒙线性免疫法检测抗ENA抗体,并采用双盲法分析ANA阳性标本的荧光核型与抗ENA抗体的关系。结果 1084例临床标本中,ANA阳性的标本数399例,阳性率为36.81%（399/1084）。512例标本联合检测ANA抗体和抗ENA抗体。ANA阳性标本数为169例。其核型包括核均质型（122例）、核斑点型（31例）、核周型（12例）、混合型（4例）。抗ENA抗体阳性标本数161例,其中80例标本抗ENA抗体阳性且ANA阴性,有88例标本抗ENA抗体阴性且ANA阳性。在169例ANA阳性的标本中,主要的荧光核型是核均质型。而核均质型ANA标本中,常见的抗ENA抗体是抗Ro/SSA60抗体（35例）。核斑点型ANA标本中,常见的抗ENA抗体是R0/SSA 60抗体（14例）、抗U1RNP（7例）、抗Sm（9例）。核周型ANA标本中,常见的抗ENA抗体是抗R0/SSA60（5例）、抗dsDNA（6例）、抗核小体抗体（5例）、抗组蛋白抗体（5例）。结论 ANA与抗ENA抗体这两种检测方法的吻合程度不佳,ANA的荧光核型与抗ENA抗体类型没有固定的规律。用间接免疫荧光法筛查ANA,并联合抗ENA抗体谱进行分型,才能确定部分ANA靶抗原的类型,必须进一步扩大抗ENA抗体谱。     

297例自身免疫性疾病ANA和抗ENA抗体联合检测分析

目的分析其中ANA表达阳性而抗ENA抗体表达阴性的样本的检验学特征及意义。方法对297例样本运用间接免疫荧光法检测ANA,生物芯片技术检测抗ENA抗体,并采用双盲法分析ANA阳性标本的荧光核型。从已知的ANA阳性患者血清中筛选其ENA表达均为阴性的患者血清,比对其荧光核型并进行分析。结果 297例临床标本中,ANA阳性标本数为74例,阳性率为24.9%(74/297)。其主要核型为核浆颗粒型(43例,58.1%)、胞浆颗粒型(9例,12.2%)、核浆点型(9例,12.2%)。在74例ANA阳性标本中,抗ENA抗体为阴性的标本数为13例,占阳性标本的17.6%。13例标本中有11例表现为核浆颗粒型,占84.6%;1例表现为胞浆颗粒型,占7.7%;1例表现为核浆点型,占7.7%。结论在ANA阳性同时抗ENA抗体表达为阴性的患者血清中,核浆颗粒型明显高于胞浆颗粒型与核浆点型在ANA标本中的阳性率,并且远大于核浆颗粒型在抗ENA抗体表现为阳性的ANA阳性标本中的比例(52.5%),差异有统计学意义(χ2=5.018,P0.05)。在抗ENA抗体表现为阴性的ANA阳性标本中,荧光核型表现为核浆颗粒型有其自身特有的临床意义有助于筛选发现抗ENA抗体以外的新自身抗体。     

抗核抗体核型与抗核抗体谱3(IgG)相应抗体的关系研究

目的 探讨抗核抗体(ANA)荧光核型与ANA 谱3(IgG)15 项抗体之间的关系.方法 对济宁医学院附属医院门诊及住院的自身免疫性疾病(AID)患者进行检测,ANA 采用间接免疫荧光法检测,ANA 谱3(IgG)15 项抗体采用欧蒙免疫印记法检测.结果 362 例ANA 阳性标本中单一核型中核均质型72 例,核颗粒型135 例,胞浆颗粒型26 例,核仁型11 例,着丝点型20 例,核膜型1 例,细胞骨架型2 例,高尔基体型1 例,其余为混合核型,其中ANA 谱3(IgG)15 项抗体阳性率为84.3%(305/362).核均质型常见抗体为抗核小体、Ro-52、dsDNA、组蛋白抗体.核颗粒型常见抗体为抗Ro-52、SSA、nRNP、SSB、Sm 和抗RIB 抗体.胞浆颗粒型常见抗体为抗Ro-52、SSA 和抗RIB 抗体.结论 ANA 是AID 的筛查实验,而ANA 谱3(IgG)15 项抗体对于AID 具有鉴别意义,两者需要平行检测,防止漏诊,通过核型找到ANA 谱3(IgG)15 项抗体中相对应的阳性抗体,提高诊断率.     

抗核抗体与抗β2糖蛋白-1抗体水平的相关性研究

目的探讨抗核抗体(ANA)阳性患者是否存在更高的血栓或病理妊娠风险。方法收集2019年5月至2020年8月该院检验科常规检测ANA谱的新鲜血清标本125例,其中ANA阳性患者(ANA阳性组)标本80例,ANA阴性患者(ANA阴性组)标本45例。采用化学发光免疫分析法分别进行抗β2糖蛋白-1(β2GP-1)抗体定量检测,然后进行统计学处理和相关性分析。结果 ANA阳性组女性占比81.3%,ANA阴性组女性占比51.1%,差异有统计学意义(P0.05)。两组抗多发性肌炎硬皮病(PM-Scl)抗体阳性例数比较,差异无统计学意义(P0.05),其余抗体阳性例数比较差异均有统计学意义(P0.05)。ANA阳性组ANA核型、滴度与抗β2GP-1抗体水平的相关性分析显示,ANA核型、滴度与抗β2GP-1抗体水平之间不存在线性相关性(P0.05)。结论 ANA阳性患者与ANA阴性患者相比更容易伴随抗β2GP-1抗体阳性,但是ANA核型、滴度与抗β2GP-1抗体水平之间不存在线性相关性,推断ANA阳性患者存在潜在更高的血栓或不良妊娠风险。     

312例抗核抗体与抗细胞核细胞浆抗体谱检测结果的分析

目的 回顾分析抗核抗体(ANA)与抗细胞核细胞浆抗体谱(ANA谱)在本实验室的应用状况,以及在自身免疫性疾病诊断上的价值.方法 ANA用间接免疫荧光法检测,ANA谱用欧蒙印迹法检测.结果 312例临床标本中,ANA阳性数为123例,阳性率为39.9%(123/312),核型种类主要为核细颗粒型、均质型和核仁型等,滴度各有不同.312例标本同时做ANA谱检测,阳性数为88例,阳性率为25%(88/312).阳性抗体出现次数较多的是抗SSA、Ro52、SSB、CENPB(着丝点B蛋白)和Histone(组蛋白)等,基本上与荧光法测定ANA核型的结果相符.只是当ANA为低滴度(起始滴度1:100)时,ANA谱为阴性结果的可能性较高.结论 用间接免疫荧光法筛查ANA,再用ANA谱作确认分型,可以更准确地确定ANA靶抗原的类型,ANA谱可检测15种针对细胞核和细胞浆的抗体,同传统的抗ENA抗体六项相比,扩大了检测范围,增强了对ANA的分型能力,具有较高的应用价值.     

Anti-neutrophil cytoplasm antibodies, anti-GBM antibodies and anti-dsDNA antibodies in glomerulonephritis

The diagnostic potential of assays detecting anti-neutrophil cytoplasm antibodies (ANCA), anti-GBM antibodies and anti-dsDNA antibodies was evaluated by examining sera from time of admission in a consecutive series of 455 patients with biopsy verified primary or secondary glomerulonephritis (GN). ANCA were classified into c- and p-ANCA by indirect immunofluorescence (IIF) and ELISAs using alfa-granule extract, proteinase-3, myeloperoxidase (MPO), elastase and lactoferrin. C-ANCA was virtually confined to 64 patients with systemic small vessel vasculitis, 66-74% being c-ANCA positive. P-ANCA against MPO, seen in 47 patients, segregated through many diagnostic categories of primary and secondary severe GN. ANCA against lactoferrin and elastase were rare. Anti-dsDNA positive patients constituted 57% of the 44 ANA-positive patients with systemic lupus erythematosus. It is concluded that the IIF and ELISAs for anti-proteinase-3, anti-MPO, anti-dsDNA and anti-GBM have an acceptable performance and are useful in the primary diagnostic work-up of patients suspected for secondary GN as the majority of such patients will be classified by these assays.     

Non-fucosylated therapeutic antibodies as next-generation therapeutic antibodies

Most of the existing therapeutic antibodies that have been licensed and developed as medical agents are of the human IgG1 isotype, the molecular weight of which is ～ 150 kDa. Human IgG1 is a glycoprotein bearing two N-linked biantennary complex-type oligosaccharides bound to the antibody constant region (Fc), in which the majority of the oligosaccharides are core fucosylated, and it exercises the effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity through the interaction of the Fc with either leukocyte receptors (FcγRs) or complement. Recently, therapeutic antibodies have been shown to improve overall survival as well as time to disease progression in a variety of human malignancies, such as breast, colon and haematological cancers, and genetic analysis of FcγR polymorphisms of cancer patients has demonstrated that ADCC is a major antineoplasm mechanism responsible for clinical efficacy. However, the ADCC of existing licensed therapeutic antibodies has been found to be strongly inhibited by serum due to nonnpecific IgG competing for binding of the therapeutics to FcγRIIIa on natural killer cells, which leads to the requirement of a significant amount of drug and very high costs associated with such therapies. Moreover, enhanced ADCC of non-fucosylated forms of therapeutic antibodies through improved FcγRIIIa binding is shown to be inhibited by the fucosylated counterparts. In fact, non-fucosylated therapeutic antibodies, not including the fucosylated forms, exhibit the strongest and most saturable in vitro and ex vivo ADCC among such antibody variants with improved FcγRIIIa binding as those bearing naturally occurring oligosaccharide heterogeneities and artificial amino acid mutations, even in the presence of plasma IgG. Robust stable production of completely non-fucosylated therapeutic antibodies in a fixed quality has been achieved by the generation of a unique host cell line, in which the endogenous α-1,6-fucosyltransferase (FUT8) gene is knocked out. Thus, the application of non-fucosylated antibodies is expected to be a promising approach as next-generation therapeutic antibodies with improved efficacy, even when administrated at low doses in humans in vivo. Clinical trials using non-fucosylated antibody therapeutics are underway at present.     

Non-fucosylated therapeutic antibodies as next-generation therapeutic antibodies

Most of the existing therapeutic antibodies that have been licensed and developed as medical agents are of the human IgG1 isotype, the molecular weight of which is approximately 150 kDa. Human IgG1 is a glycoprotein bearing two N-linked biantennary complex-type oligosaccharides bound to the antibody constant region (Fc), in which the majority of the oligosaccharides are core fucosylated, and it exercises the effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity through the interaction of the Fc with either leukocyte receptors (FcgammaRs) or complement. Recently, therapeutic antibodies have been shown to improve overall survival as well as time to disease progression in a variety of human malignancies, such as breast, colon and haematological cancers, and genetic analysis of FcgammaR polymorphisms of cancer patients has demonstrated that ADCC is a major antineoplasm mechanism responsible for clinical efficacy. However, the ADCC of existing licensed therapeutic antibodies has been found to be strongly inhibited by serum due to nonnpecific IgG competing for binding of the therapeutics to FcgammaRIIIa on natural killer cells, which leads to the requirement of a significant amount of drug and very high costs associated with such therapies. Moreover, enhanced ADCC of non-fucosylated forms of therapeutic antibodies through improved FcgammaRIIIa binding is shown to be inhibited by the fucosylated counterparts. In fact, non-fucosylated therapeutic antibodies, not including the fucosylated forms, exhibit the strongest and most saturable in vitro and ex vivo ADCC among such antibody variants with improved FcgammaRIIIa binding as those bearing naturally occurring oligosaccharide heterogeneities and artificial amino acid mutations, even in the presence of plasma IgG. Robust stable production of completely non-fucosylated therapeutic antibodies in a fixed quality has been achieved by the generation of a unique host cell line, in which the endogenous alpha-1,6-fucosyltransferase (FUT8) gene is knocked out. Thus, the application of non-fucosylated antibodies is expected to be a promising approach as next-generation therapeutic antibodies with improved efficacy, even when administrated at low doses in humans in vivo. Clinical trials using non-fucosylated antibody therapeutics are underway at present.     

Antiphospholipid antibodies

Antiphospholipid antibodies (APAs) have been associated with thromboembolic events. Since they were fi rst described in 1906, APAs have been the subject of multidisciplinary studies seeking to link them to potential pathophysiologic mechanisms. This review summarizes the different types of APAs, antigenic targets, clinical complications associated with APAs, and APA syndrome. In addition, the currently available methods for laboratory identification of lupus anticoagulants are discussed, as is the laboratory diagnosis of anticardiolipin antibodies.