抗核抗体

近年由于免疫学的发展,对结缔组织病(简称 CTD)本质的认识,以及在诊断方面都有了很大提高。抗核抗体(简称 ANA)以及补体、免疫复合物的测定等,对诊断 CTD 都起着重要作用。本文仅对 ANA 作一概述。ANA 又名抗核因子(ANF),是泛指一类具有抗各种核内成份的一种自身抗体。     

抗甲状腺激素抗体

抗甲状腺激素抗体是针对血清三碘甲腺原氨酸（T3）和甲状腺素（T4）的一类特异性免疫球蛋白，即抗T3抗体（T3Ab）和抗T4抗体（T4Ab）[1～3]。本文简介此类抗体的研究概况。一、抗甲状腺激素抗体的性质和作用抗甲状腺激素抗体是一类特异性的免疫球蛋白G（lgG）－‘－‘j，其结合     

抗胰岛细胞抗体抗胰岛素抗体与抗谷氨酸脱羧酶抗体在糖尿病诊断中的意义

现已发现1型糖尿病人至少有三种胰岛细胞抗原成分的自身抗体，分别特异性对应于胰岛细胞抗原组分、胰岛素和谷氨酸脱羧酶。为了糖尿病正确分型、早期预报、分析糖尿病的病因，我室对这类患者检测抗胰岛细胞抗体(ICA)、抗胰岛素抗体(IAA)及抗谷氨酸脱羧酶抗体(GADA)，探讨其在鉴别1型糖尿病和早期诊断成人晚发性自身免疫性糖尿病(LADA)中的临     

抗细胞因子自身抗体

输注重组细胞因子可导致患者产生抗细胞因子自身抗体,T细胞免疫耐受的消失是健康个体含有高亲和力抗细胞因子自身抗体的原因,从而导致输注IgG制品者体内含有多种抗细胞因子自身抗体,造成细胞因子治疗失效.细胞因子疫苗可用于抗细胞因子治疗.临床上值得关注的是,抗细胞因子抗体会干扰某些细胞因子的测定,某些抗细胞因子抗体水平可判断免疫炎性疾病的预后.     

抗中性粒细胞胞浆抗体、抗核抗体联合检测

目的 探讨抗中性粒细胞胞浆抗体(ANCA)与抗核抗体联合检测的临床意义.方法 应用间接免疫荧光法(IIF)检测疑似自身免疫性疾病患者血清中的ANCA和抗核抗体(ANA),并用ELISA法进行抗丝氨酸蛋白酶3(PR3)和抗髓过氧化物酶(MPO)的定量检测.结果 (1)在ANA阳性组和ANA阴性组中均检出ANCA,但ANA阳性组的阳性率(15.64%)高于ANA阴性组(3.25%)(P＜0.01).(2)ANCA阳性组以抗MPO和抗PR3升高为主,与ANCA阴性组比较有统计学差异(P＜0.01).结论 同时进行ANCA、ANA检测,有助于提高自身免疫性疾病的诊断.     

抗细胞因子自身抗体

输注重组细胞因子可导致患者产生抗细胞因子自身抗体,T细胞免疫耐受的消失是健康个体含有高亲和力抗细胞因子自身抗体的原因。从而导致输注IgG制品者体内含有多种抗细胞因子自身抗体,造成细胞因子治疗失效。细胞因子疫苗可用于抗细胞因子治疗,临床上值得关注的是,抗细胞因子抗体会干扰某些细胞因子的测定。某些抗细胞因子抗体水平可判断免疫炎性疾病的预后。     

抗卵巢抗体和抗绒毛膜促性腺激素抗体在继发性不孕中的意义

目的探讨抗卵巢抗体（AOAb）和抗绒毛膜促性腺激素抗体（AHCGAb）与人工流产后继发不孕的关系。方法选择2007年1月～2009年12月间，98例人工流产后不孕妇女作为研究组，另选择95例原发性不孕症患者作为对照a组，90例正常育龄妇女为对照b组，用酶联免疫吸附法（ELISA）分别测定两组妇女血清中的AOAb和AHCGAb。结果研究组较对照b组AOAb和AHCGAb均高，差异均极有显著性（P〈0．01）;研究组与对照a组比较AHCGAb高，差异有显著性（P〈0．05），而AOAb在二者之间差异无显著性（P〉0．05）对照a组AOAb和AHCGAb均高于对照b组，差异有显著性（P〈0．05）。结论AOAb和AHCGAb可能是人工流产后引起女性免癌件不孕的雷要因素之一．     

自身免疫性疾病抗核抗体与抗ENA抗体相关分析

目的比较抗ENA(可提取性核抗原)抗体与抗核抗体(ANA)荧光核型之间的相关分析。方法ANA采用间接免疫荧光法检测,抗ENA抗体采用欧蒙斑点法检测。结果314例ANA阳性标本中抗ENA抗体阳性率90.4%(284/314)。ANA135例颗粒型阳性占抗ENA抗体常规6项检测阳性的47.5%(135/284)。抗ENA抗体中抗nRNP/Sm、抗Sm、抗SSA、抗SSB抗体一项或多项阳性时ANA颗粒型占72.6%(98/135),显示ANA多为颗粒型(斑点)或合并有其他核型;抗SSA、SSB抗体阳性时颗粒型占35.5%(22/62);抗ScI-70抗体阳性时核仁型所占比例较高,阳性率80.0%(16/20)。结论ANA是自身免疫性疾病(AID)的筛查实验,而抗ENA抗体对于自身免疫性疾病具有鉴别意义,两者需要平行检测。     

SLE患者抗ENA抗体及抗DNA抗体的检测分析

为探讨系统性红斑狼疮 ( SLE)患者血清中抗 ENA抗体与抗 DNA抗体的关系及意义 ,对 88例 SL E患者分别测定血清中抗 ss-DNA抗体、抗 ds-DNA抗体及 7种抗 ENA抗体。结果显示 ,88例 SLE患者中有 65例 ( 73 .5 % )检测到至少一种抗 ENA抗体 ,以抗 Sm、抗 U1 RNP和抗 SSA为主 ,分别占 45 .5 %、5 2 .3 %及 40 .9% ,其次为抗 SSB及抗 Rib,分别占 2 5 .0 %及 15 .9%。 88例SLE患者的 7种自身抗体与抗 ds-DNA抗体总的阳性符合率为 75 .2 % ,与抗 ss-DNA抗体总的阳性符合率为 60 .2 %。因此 ,抗 ENA抗体与抗 DNA抗体同时检测有助于提高 SLE的诊断阳性率。     

抗体药物的药学监护

近年来，抗体药物在自身免疫性疾病及肿瘤治疗领域表现非凡，成为当前药物研发的热点之一。与传统小分子药物相比，抗体药物具有结构功能复杂、药动学特殊及免疫原性等特点，使其对临床合理用药提出了新的挑战。本文以抗体药物的结构和药动学特征为基础，从抗体药物的有效性、安全性、经济性、免疫原性和药物警戒五个方面，阐述如何将药学监护手段应用于抗体药物，旨在为抗体药物的临床合理使用提供参考。     

Anti-epitope antibody, a novel site-directed antibody against human acetylcholinesterase

AIM: To construct synthetic antigens using the epitope of human brain acetylcholinesterase (hbAChE) for induc- tion and detection of the specific antibody against the epitope, and to analyse the immunogenicity of the antibody. METHODS: The epitope (RTVLVSMNYR, amino acids 143-152) of hbAChEwas chemically synthesized, coupled with the carrier protein keyhole limpet hemocyanin (KLH) to construct an artificial immunogen (KLH-epitope), and injected into rabbits to raise antibody. T…     

Monoclonal antibody technology

The development, production, limitations, and uses of monoclonal antibody (MoAb) technology are presented. The first MoAbs were developed in 1975 using a process whereby the antibody-producing spleen cells of mice that had been immunized against sheep red blood cells were fused with the cells of a mouse myeloma cell line, producing hybridomas. These hybridoma cells are used to produce MoAbs, which are antibodies that will bind to only one specific target site on an antigen. Large quantities of MoAbs are grown, either in cell cultures or in the peritoneum of mice, and harvested. Although large quantities of MoAbs can be produced, these techniques are limited because of the potential for contamination by mouse viruses and the inability of the hybridomas to yield sufficient quantities of MoAbs. MoAbs are currently used in diagnostic techniques, including pregnancy tests and drug assays, as well as in tests for detecting viral and bacterial infections and cancer. MoAbs, coupled with dyes or radioactive isotopes, can be used in imaging techniques. Other possible applications of MoAbs include tissue typing, purification, therapy of cancer and autoimmune diseases, and treatment of drug toxicities. As the use of MoAbs in health care increases, pharmacists will need to have a good understanding of the functions and applications of these agents.     

Self-buffering antibody formulations

Monoclonal antibodies (mAbs) often require the development of high-concentration formulations. In such cases, and when it is desirable to formulate a mAb around pH 5.0, we explored a novel approach of controlling the formulation pH by harnessing the ability of mAbs to "self-buffer." Buffer capacities of four representative IgG(2) molecules (designated mAb1 through mAb4) were measured in the pH 4-6 range. The buffer capacity results indicated that the mAbs possessed a significant amount of buffer capacity, which increased linearly with concentration. By 60-80 mg/mL, the mAb buffer capacities surpassed that of 10 mM acetate, which is commonly employed in formulations for buffering in the pH 4-6 range. Accelerated high temperature stability studies (50 degrees C over 3 weeks) conducted with a representative antibody in a self-buffered formulation (50 mg/mL mAb1 in 5.25% sorbitol, pH 5.0) and with solutions formulated using conventional buffers (50 mg/mL mAb1 in 5.25% sorbitol, 25 or 50 mM acetate, glutamate or succinate, also at pH 5.0) indicated that mAb1 was most resistant to the formation of soluble aggregates in the self-buffered formulation. Increased soluble aggregate levels were observed in all the conventionally buffered (acetate, glutamate, and succinate) formulations, which further increased with increasing buffer strength. The long-term stability of the self-buffered liquid mAb1 formulation (60 mg/mL in 5% sorbitol, 0.01% polysorbate 20, pH 5.2) was comparable to the conventionally buffered (60 mg/mL in 10 mM acetate or glutamate, 5.25% sorbitol, 0.01% polysorbate 20, pH 5.2) formulations. No significant change in pH was observed after 12 months of storage at 37 and 4 degrees C for the self-buffered formulation. The 60 mg/mL self-buffered formulation of mAb1 was also observed to be stable to freeze-thaw cycling (five cycles, -20 degrees C --> room temperature). Self-buffered formulations may be a better alternative for the development of high-concentration antibody and protein dosage forms.     

测定抗心磷脂抗体、抗心肌线粒体抗体在诊治扩张型心肌病中的意义

目的比较抗心磷脂抗体(ACA)和抗心肌线粒体抗体(ACMA)对扩张型心肌病(DCM)诊断及治疗评估价值。方法采用ELISA法测定DCM,30例患儿ACA-lgG和ACMA-lgG,并与健康者对照,同时检测心肌酶、心电图和多普勒超声心动图。结果DCM患儿ACA-lgG和ACMA-lgG阳性率分别为53.3%和40.0%,均显著高于健康者(P<0.01)。ACA-G阳性患儿心肌酶CK-MB、心律失常发生率、心腔扩大率、左心收缩功能降低率均显著高于ACA-lgG阴性者(P<0.05);而ACMA-lgG阳性与否同上述改变无明显相关性(P>0.05)。结论ACA-lgG阳性对DCM患者诊断和病情轻重判定均有重要意义;ACMA-lgG阳性虽对DCM患儿诊断有一定价值,但对病情判断无作用。     

Belimumab: anti-BLyS human monoclonal antibody, anti-BLyS monoclonal antibody, BmAb, human monoclonal antibody to B-lymphocyte stimulator

Belimumab is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS. Belimumab is in phase III trials for the treatment of systemic lupus erythematosus (SLE) and has completed a phase II trial in rheumatoid arthritis (RA); the product may also have potential in the treatment of other autoimmune disorders. In May 2001, Cambridge Antibody Technology (now MedImmune) completed its discovery programme and Human Genome Sciences identified belimumab as a candidate for clinical development. More than 1000 distinct human antibodies specific to BLyS were characterized by the collaboration.B-lymphocyte stimulator is a naturally occurring protein discovered by Human Genome Sciences that stimulates B-lymphocytes to develop into mature B cells. Laboratory studies have indicated that higher than normal levels of B-lymphocyte stimulator may contribute to the pathogenesis of autoimmune diseases, such as SLE and RA. Human Genome Sciences (HGS) and Cambridge Antibody Technology signed a collaborative agreement in August 1999 to study the B-lymphocyte stimulator as a human protein target. HGS is also developing other BLyS products. In March 2000, HGS and Cambridge Antibody Technology expanded their agreement into a 10-year collaboration and product development alliance, providing Human Genome Sciences with the right to use the antibody technology of Cambridge Antibody Technology to fully develop human antibodies for therapeutic and diagnostic purposes. Cambridge Antibody Technology will receive royalty payments on product sales from HGS, as well as the development and milestone payments it has already received. Belimumab will be manufactured in Human Genome Sciences' manufacturing facility, located in Rockville, MD, USA. HGS holds commercial rights to the drug. In July 2005, GlaxoSmithKline (GSK) exercised its co-development and co-promotion option to belimumab. In an agreement made in June 1996, HGS had granted a 50/50 co-development and co-promotion option to GSK for certain therapies that complete phase IIa trials successfully. The companies subsequently entered into a definite worldwide, co-development and commercialization agreement in August 2006, under which HGS will be responsible for conducting phase III trials of the product, with assistance from GSK. The companies will share equally phase III/IV development costs, sales and marketing expenses, and profits. In October 2007, Cambridge Antibody Technology was integrated into MedImmune. Both companies were previously independent subsidiaries of AstraZeneca. MedImmune is now the operationally independent biologics business unit of AstraZeneca. Human Genome Sciences intends to initiate a phase II trial of subcutaneous belimumab by mid-2008. Results from a phase II trial in 449 patients with SLE demonstrated that belimumab improved or stabilized SLE over 2.5 years. The phase II trial was a double-blind, placebo-controlled, multicentre study that evaluated the safety, optimal dosing, and preliminary efficacy of belimumab in patients with active SLE over 52 weeks initially, followed by a continuation phase for a total of 2.5 years. Belimumab has received fast-track designation for the treatment of SLE from the US FDA and has also been selected for inclusion in the agency's continuous Marketing Application Pilot 2 programme.