儿童糖尿病自身抗体检测及其临床意义

[目的]了解儿童糖尿病胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)和胰岛素自身抗体(IAA)阳性率及其与儿童胰岛功能的关系,评价自身抗体测定对1型糖尿病的诊断价值。[方法]用间接酶联免疫吸附法检测 GA- DA、ICA 和 IAA,放射免疫法测定基础 C 肽(BCP)和胰高血糖索刺激后6分钟 C 肽(PGCP)。[结果]1型糖尿病患者 GADA、ICA 和 IAA 的阳性率分别为44．9%、53．1%和28．6%高于正常对照组(P＜0．05)。抗体阳性组 BCP(0．21± 0．18 ng/ml)和 PGCP(0．36±0．24 ng/ml)低于抗体阴性组(0．69±0．35 ng/ml；1．06±0．61 ng/ml)。3种自身抗体联合检测1型糖尿病的敏感性、特异性、阳性预测值、阴性预测值分别为87．8%、75．0%、84．3%和80．0%。[结论]自身抗体阳性患者胰岛功能有明显损伤；GADA、ICA,IAA 是1型糖尿病的重要免疫学标志,3种抗体联合检测可提高诊断率,对1型糖尿病有重要诊断价值。     

胰岛自身抗体测定对成人隐匿性自身免疫糖尿病的诊断价值

目的:探讨谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)和抗胰岛素抗体(IAA)在成人隐匿性自身免疫糖尿病(LADA)诊断中的价值。方法:入选150例初诊为2型糖尿病(T2DM)的患者和80例正常糖耐量者,测定其血清GADA、ICA和IAA,并行胰岛素释放试验及C肽释放试验。结果:初诊为T2DM患者血清中GADA、ICA及IAA抗体的阳性率分别为20.0%、14.0%和8.0%,有一种或以上抗体阳性者占30%。与对照组比较,血清中有一种或以上胰岛自身抗体阳性的DM患者的胰岛素和C肽分泌水平明显下降,其中三种抗体全阳性组患者下降最为显著,差别均有统计学意义(P<0.01)。结论:临床初诊为T2DM的病人中存在被误诊的LADA患者,多种胰岛自身抗体联合检测可提高LADA的检出率。     

糖尿病患者胰岛自身抗体检测的临床意义

目的探讨胰岛自身抗体在糖尿病诊断中的意义。方法采用ELISA法分别检测I型DM、成人隐匿性自身免疫性糖尿病(LADA)、II型DM患者血清谷氨酸脱羧酶抗体(GAD)、胰岛细胞抗体(ICA)、胰岛素自身抗体(IAA);并对DM患者空腹血糖及C肽和餐后120minC肽进行检测。结果I型糖尿病患者GAD的阳性率为41.2%,ICA为35.3%,IAA为23.5%;LADA组GAD的阳性率为28.6%,ICA和IAA均为21.4%,两组与II型DM组相比,有显著性差异。胰岛抗体阳性与阴性DM患者相比,在起病年龄、病程、空腹血糖及C肽均有显著性差异。结论胰岛自身抗体的检测对糖尿病的正确分型具有重要的指导作用。     

早发2型糖尿病继发性磺脲类药物失效患者ICA和GADA检测的意义

目的探讨早发2型糖尿病继发性磺脲类药物失效患者胰岛细胞抗体(ICA)和谷氨酸脱羧酶抗体(GADA)检测的情况及临床意义。方法46例早发2型糖尿病继发性磺脲类药物失效患者(SF组)和48例早发2型糖尿病使用饮食和/或磺脲类药物血糖控制良好患者(对照组),分别测定两组患者的ICA和GADA以及进食100g面粉的馒头分别测定0、1、2、3h的血糖、胰岛素、C肽。结果SF组ICA和GADA阳性率明显高于对照组(P<0.001),并与胰岛B细胞功能呈负相关。结论早发2型糖尿病继发性磺脲类药物失效患者ICA、GADA的阳性率明显升高,胰岛B细胞功能更差,自身免疫机制可能是早发2型糖尿病患者继发性磺脲类药物失效的机制之一。成人隐匿性自身免疫糖尿病(LADA)可能是早发2型糖尿病患者继发性磺脲类药物失效的病因之一。     

早发2型糖尿病继发性磺脲类药物失效患者ICA和GADA检测的意义

目的探讨早发2型糖尿病继发性磺脲类药物失效患者胰岛细胞抗体（ICA）和谷氨酸脱羧酶抗体（GADA）检测的情况及临床意义。方法46例早发2型糖尿病继发性磺脲类药物失效患者（SF组）和48例早发2型糖尿病使用饮食和／或磺脲类药物血糖控制良好患者（对照组），分别测定两组患者的ICA和GADA以及进食100g面粉的馒头分别测定0、1、2、3h的血糖、胰岛素、C肽。结果SF组ICA和GADA阳性率明显高于对照组（P〈0．001），并与胰岛B细胞功能呈负相关。结论早发2型糖尿病继发性磺脲类药物失效患者ICA、GADA的阳性率明显升高，胰岛B细胞功能更差，自身免疫机制可能是早发2型糖尿病患者继发性磺脲类药物失效的机制之一。成人隐匿性自身免疫糖尿病（LADA）可能是早发2型糖尿病患者继发性磺脲类药物失效的病因之一。     

三种自身抗体联合检测对成人隐匿性自身免疫性糖尿病的诊断价值

目的通过对血清谷氨酸脱羧酶抗体(GAD-Ab)、酪氨酸磷酸酶样蛋白抗体(IA-2A)和胰岛细胞抗体(ICA)联合检测,探讨其对成人隐匿性自身免疫性糖尿病(LADA)的诊断价值。方法用ELISA法测定157例临床诊断为2型糖尿病患者及49例健康查体者的血清GAD-Ab、IA-2A和ICA,并比较抗体阳性和阴性患者的临床特征。结果临床诊断为2型糖尿病的患者GAD-Ab、IA-2A和ICA的阳性率与对照组比较差异有统计学意义(χ2=8.10,8.51,P<0.01;χ2=4.08,P<0.05),且ICA的阳性率低于GAD-Ab、IA-2A阳性率(χ2=5.78,P<0.05);抗体阳性组患者空腹及餐后2 h血清C肽水平较抗体阴性组明显降低(t=9.606,11.175,P<0.001)。结论胰岛自身抗体联合检测可提高LADA患者的检出率;LADA患者胰岛储备功能较差。     

检测谷氨酸脱羧酶和胰岛细胞抗体早期诊断成人迟发性自身免疫性糖尿病

目的 :通过谷氨酸脱羧酶抗体 (GADA)和胰岛细胞抗体 (ICA)的检测 ,探讨其对成人迟发性自身免疫性糖尿病 (LADA)早期诊断的价值。方法 :12 5例 30岁以后起病的开始无酮症、非胰岛素依赖≥ 6个月的糖尿病 (DM )患者。其中 72例为需要胰岛素治疗的DM (ITDM )组 ,按 10 0g馒头餐刺激前后的血清CP水平分为两个亚组 :胰岛素缺乏组 (n =35 )和非胰岛素缺乏组 (n =37) ;另外 5 3例为口服降糖药 (OHA)治疗有效的 2型DM (OHA组 )。GADA和ICA的检测采用酶联免疫吸附试验 (ELISA)。结果 :ITDM组 31 9%GADA( ) ,19 4%ICA( ) ,明显高于OHA组 3 8%和 0 (P <0 .0 0 5 ) ;胰岛素缺乏组和非胰岛素缺乏组的GADA阳性率分别是 48 6 %和 15 8% (P <0 .0 0 5 ) ;ICA的阳性率分别是 31 4%和 7 9% (P <0 .0 5 ) ;GADA( )者与GADA(- )者相比 ,其BMI低 (P <0 .0 0 1) ,ICA阳性率高 (P <0 .0 0 5 ) ,血清CP水平低 (P <0 .0 1)。结论 :GADA和ICA的联合检测可以提高LADA诊断的敏感性 ,但GADA优于ICA。对于胰岛功能差、非肥胖、GADA和 /或ICA( )的成年DM患者应该尽早使用胰岛素和免疫干预治疗。     

成人缓发性自身免疫性糖尿病诊断标准探讨

目的探讨LADA的诊断指标。方法对168例2型糖尿病患者及100例健康个体进行身高、体重、血糖(空腹及餐后)、C肽(空腹及餐后),以及GADA、ICA、IAA、IA-2等检测。2型糖尿病中抗体阳性者为LADA组,抗体阴性者仍为2型糖尿病。结果GADA、ICA、IAA及IA-2在2型糖尿病组分别为21.18%、14.29%、1.19%及0.60%(GDAA vs ICA/IA-2:21.43%vs14.29%/1.19%,χ2=2.68/33.29,P=0.09/0.00;ICA vs IA-2:14.29%vs 1.19%,χ2=21.09,P=0.00)。发病年龄≤40岁、发病时明显三多一少症状、酮症、无慢性并发症、无高血压、BM I<18.5 kg/m2、FBG≥18.5 mmol/L、FC-P<0.30 nmol/L作为LADA诊断指标,其特异性或阴性预测值较高(90.00%以上)。结论GADA是糖尿病最有价值免疫学指标。发病年龄≤40岁、发病时有症状、酮症、无慢性并发症、无高血压、BM I<18.5 kg/m2、FBG≥18.5 mmol/L、FC-P<0.30 nmol/L可作为LADA临床诊断参考指标。     

自身抗体阳性妊娠期糖尿病与HLA-DRB1基因型相关分析

目的:评估胰岛自身抗体阳性的妊娠期糖尿病(GDM)孕妇人类白细胞抗原DRB1位点(HLA-DRB1)基因频率分布及HLA-DRB1基因与其妊娠结局的相关性。方法:对2004年在我院产检无糖尿病史的广东省籍汉族GDM孕妇116例,测定谷氨酸脱羧酶抗体(GADA),胰岛细胞抗体(ICA)和胰岛素自身抗体(IAA),以及用序列特异性引物杂交技术(PCR-SSOPH)进行HLA-DRB1基因分型。抗体阳性的42例纳入研究组,抗体阴性的74例为对照组。比较两组GDM孕妇的妊娠结局和产后6周血糖情况。结果:研究组的孕妇比对照组孕前BMI较低,妊娠失败可能性较高。1型糖尿病相关的HLA-DRB1基因频率分布在两GDM组间差异无显著性,但两组HLA-DRB1*04-频率均高于正常人群(P<0.01)。结论:自身抗体阳性的GDM孕妇可能有1型糖尿病遗传背景和免疫反应,应严密监护,加强随访。     

成人晚发性自身免疫性糖尿病自身免疫抗体的研究进展

成人晚发性自身免疫性糖尿病(LADA)属于Ⅰ型糖尿病(DM)的亚型，其早期临床表现与2型DM相似，胰岛B细胞所受的免疫损伤呈缓慢性，数年后需胰岛素治疗。本病具有低C肽水平、低体质指数等趋向于Ⅰ型DM的临床特点，血清谷氨酸脱羧酶抗体(GADAb)、胰岛细胞抗体(ICA)等自身免疫抗体阳性。由于检测方法、研究类型以及人种、地区的差异，LADA在DM中所占的比例(按GADAb、ICA的阳性率计算)，各家报道不一。Zimmet认为，在成人起病的DM患者中有10%-20％为LADA。     

HIV vaccine development: challenges and opportunities towards solving the HIV vaccine-neutralizing antibody problem

Recent advances in HIV vaccine development have created a renaissance in the search for a safe and effective HIV vaccine. These advances include the first demonstration in human clinical trials of a vaccine candidate that provided modest levels of protection from HIV infection; a series of candidates entering into clinical trials with an improved profile of protection against SIV in non-human primate studies, and the identification from HIV infected individuals of new broad and potent monoclonal antibodies against HIV that target conserved, vulnerable regions of the HIV envelope glycoprotein spike. The major challenge for successful HIV vaccine development rests on overcoming the unprecedented hyper-variability of HIV, which likely will require induction of broadly protective neutralizing antibodies to prevent HIV infection, and broad and robust cellular immune responses to control HIV infection. This presentation will review the challenges and opportunities for development of vaccine candidates capable of eliciting broadly neutralizing antibodies against HIV.     

应用血液测定实验室诊断自身免疫性甲状腺疾病

目的探讨甲状腺球蛋白抗体(TG-Ab)、甲状腺过氧化物酶抗体(TPO-Ab)、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)对自身免疫性甲状腺疾病(AITD)的临床应用价值。方法采用化学发光免疫分析法定量检测153例自身免疫性甲状腺疾病患者、74例非自身免疫性甲状腺疾病患者和71例健康对照组血清中的TG-Ab、TPO-Ab、FT3、FT4。结果不同自身免疫性甲状腺疾病患者之间和自身免疫性甲状腺疾病患者与非自身免疫性甲状腺疾病患者及正常健康人群之间其TG-Ab、TPO-Ab、FT3、FT4水平差异有统计学意义。AITD组TG-Ab和TPO-Ab水平与非AITD组、健康对照组比较差异有统计学意义(P<0.01),桥本甲状腺炎组TG-Ab和TPO-Ab水平与Graves病组比较差异有统计学意义(P<0.01),桥本甲亢组和Graves病组FT3、FT4水平差异无统计学意义(P>0.05),而TPO-Ab、TG-Ab差异有统计学意义(P<0.01)。结论 TG-Ab、TPO-Ab、FT3、FT4四项指标对AITD的诊断及鉴别诊断有重要临床意义。     

AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats

Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.     

单克隆抗体亲和层析纯化日本脑炎病毒E糖蛋白的研究

本文探讨了用JEV—E McAb制备亲和层析柱纯化E糖蛋白的方法。结果表明,超声粉碎法裂解病毒囊膜不影响HA活性,而用NP40、去氧胆酸钠、Tri—ton X-100处理病毒原始材料,则导致HA活性的丧失;pH11.5、0.05M二乙胺洗脱剂对E的生物活性影响较少,而3M KSCN对E的HA活性有明显影响;用亲和力适中的McAb2F_2和mC_3亲和层析柱纯化E糖蛋白,其HA活性的回收率分别为30～40%及30～60%,蛋白收获量分别为0.33～1.26mg及0.21～0.66mg,相对HA比活性分别提高3～8倍及8～30倍;经SDS—PAGE考马斯亮兰染色,显示一条带,分子量相当于E糖蛋白;纯化的E糖蛋白可诱导小鼠产生HI抗体及NT抗体。     

Antibodies Against Laminin-1 and Sperm,Intraacrosomal Proteins in Semen from Infertile Couples

Seminal sperm-agglutinating antibodies along with IgG antibodies against laminin-1 and intraacrosomal sperm proteins were examined in seventy-one men from infertile couples. The direct mixed antiimmunoglobulin reaction test for IgG, IgA, and the commercial ELISA method for detecting IgG antibodies against laminin-1 in seminal plasma were used. Intraacrosomal proteins in the sperm heads were detected by immunofluorescence using monoclonal antibodies. Cellular elements other than spermatozoa, collectively referred to as “round cells” were also examined. In association with a group of oligoasthenospermatic men, positive levels (44%) of antibodies against laminin-1 of the IgG isotype in seminal plasma were found in conjunction with increased cellularity in semen. Interestingly, the elevated levels of anti-laminin-l IgG and sperm agglutinating positivity were not correlated.

The use of antibodies against sperm antigens targeted to adhesive molecules such as laminin-1 contributes to diagnosing reproductive failure. Detection of intraacrosomal proteins very often correlates to the state of semen pathology and inflammation.     

淋巴细胞主动免疫治疗复发性流产的临床研究

目的:观察淋巴细胞主动免疫治疗封闭抗体缺乏所致复发性流产的临床疗效,探讨封闭抗体对妊娠结局的意义。方法:将临床筛查确诊为封闭抗体缺乏所致的复发性流产患者100例随机分为2组,研究组50例,采用淋巴细胞主动免疫治疗。对照组50例,未行任何处理,比较两组妊娠结局。研究组治疗后常规复查封闭抗体,比较封闭抗体阳性组及阴性组妊娠结局。结果:研究组50例中,已分娩26例,16例妊娠中期,8例流产,妊娠成功率84%。对照组50例,已分娩14例,12例妊娠中期,24例流产,妊娠成功率52%,两组相比差异有显著性(P<0.01)。免疫治疗后,封闭抗体阳性组妊娠成功率88.49%(32/36),阴性妊娠成功率57.14%(8/14)。两组相比差异有显著性(P<0.05)。结论:淋巴细胞主动免疫治疗封闭抗体缺乏所致复发性流产有较可靠的临床效果及应用价值,封闭抗体对妊娠结局有一定的预示价值。     

The long term effect of age and maternally derived antibodies against foot and mouth disease on the serological response following vaccination in young dairy calves

In Israel, occurrence of foot and mouth disease (FMD) in dairy farms is rare. However, when FMD outbreaks occur, dairy calves are the most affected, despite routine vaccination. Contradictory findings exist regarding the effect of age and maternally derived antibodies (MDA) on the serological response following vaccinations against FMD in dairy calves. Furthermore, the long term effect of FMD vaccination regimen during early life was rarely assessed. This study was conducted in order to assess both the short and long term effects. In total 44 non-vaccinated calves were divided into four groups of different age. Calves were vaccinated up to four times and 484 serum samples were collected on 11 time points in a period of 70 weeks. Virus neutralizing tests were performed in order to determine the neutralizing antibody titers (NAT) against the vaccine strains (homologous serotypes): O-4625, O-Manisa, ASIA-1-Shamir and the heterologous serotype A-Turkey-20/2006. A similar NAT pattern was observed to all serotypes and therefore statistical analysis was restricted to O-4625 serotype. The MDA titer was negatively associated with the age of the calves and the MDA half-life was 22 days. We demonstrated that early vaccination of calves (younger than three months) resulted in low NAT, even after four repeated vaccinations, compared with vaccination of calves older than three months. The percentage of time in which these calves had a NAT above 2.0 (log10) between the age of six months and 1.5 years was significantly lower compared to older calves (older than three months). Additionally, we found that by increasing the frequency of vaccination in calves older than three months, it is possible to reach high NAT by the age of one year. Adoption of such a vaccination regimen in Israel as well as other FMD endemic countries may allow better protection against FMD in dairy calves and reduction in FMD incidence.     

冠心病患者血浆中抗热休克蛋白70抗体表达水平的研究

[目的 ]检测冠心病患者血浆中抗热休克蛋白 70 (HSP70 )抗体水平与正常人有无差异 ,并探讨其与冠心病发生发展之间的关系。 [方法 ]采用Western ELISA方法检测 192例冠心病患者中抗HSP70抗体水平 ,并以 192例无冠心病的个体作为对照。[结果 ] 192例冠心病患者中抗HSP70抗体阳性 7例 ,对照组 5例 ,病例组抗体阳性率与对照组之间差异无显著性 (P >0 .0 5 )。 [结论 ]本研究未发现抗HSP70抗体与冠心病的发生发展有联系 ,抗HSP70抗体在冠心病发病过程中的作用有待于进一步探讨。     

淋巴细胞主动免疫治疗复发性流产的疗效研究

[目的]探讨淋巴细胞主动免疫治疗复发性流产的疗效研究。[方法]将临床筛查确诊为封闭抗体缺乏所致的复发性流产患者100例随机分为2组,研究组50例,采用淋巴细胞主动免疫治疗;对照组50例,未行任何处理,比较两组妊娠结局。研究组治疗后常规复查封闭抗体,比较封闭抗体阳性组及阴性组妊娠结局。[结果]研究组及对照组妊娠成功率分别为82.00%(41/50)及48.00%(24/50),两组比较差异有统计学意义(P﹤0.05);免疫治疗后,封闭抗体阳性组及阴性组妊娠成功率分别为88.24%(30/34)及56.25%(9/16),两组比较差异有统计学意义(P﹤0.05)。[结论]淋巴细胞主动免疫治疗封闭抗体缺乏所致复发性流产可显著提高妊娠成功率,有较可靠的临床效果及应用价值。