Intrathyroidal T cell activation and HLA-DR antigen expression on thyroid follicular cells in autoimmune thyroid diseases]

Thyroid specimens from 19 patients with Hashimoto's thyroiditis (HT), 11 with Graves' disease (GD), 4 with nontoxic goiter (NTG), 1 with subacute thyroiditis (SAT), 1 with thyroid adenoma and 4 from normal thyroids were investigated by alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemical technique. A group of monoclonal antibodies against the corresponding T cell activation antigens were used. The positive rates of all the four activation antigens in thyroid gland mononuclear cells (TG-MNC) were significantly higher in HT than in NTG (P less than 0.05-0.01). However, the differences between HT and GD were insignificant (P greater than 0.05) except for HLA-DR antigen. The activation antigen-positive (especially TLiSA 1+) TG-MNC were often seen intruding into thyroid lumens of HT. All the abnormal specimens expressed HLA-DR antigens on thyroid follicular cells (TFC) in different degrees (+/- to +3), and the degree in HT was significantly higher than that in GD (P less than 0.01) or NTG (P less than 0.05). The level of DR expression on TFC correlated significantly with the infiltrating degrees of T-activation-antigen-positive cells (P less than 0.01). This indicates that aberrant DR expression in vivo is closely related to the activation of intrathyroidal T cells.     

类风湿关节炎患者HLA-DR4/1表型与流感病毒血凝素特异性T细胞增殖及其抗体的关系

目的 探讨类风湿关节炎(RA)患者人类白细胞抗原(HLA)-DR4/1表型与流感病毒血凝素(HA)308-317多肽特异性T细胞增殖和血清抗HA308-317抗体之间的关系.方法 将HA308-317多肽与70例RA患者外周血单个核细胞(PBMC)共孵育5 d,3H掺入法测定T细胞增殖.用ELISA法检测RA患者血清HA308-317抗体水平.以序列特异性引物聚合酶链反应(PCR.SSP)技术对RA患者进行HLA-DR分型.结果 在70例RA患者中,27例HLA-DR4/1表型阳性.其中,HA308-317多肽可刺激T细胞增殖的RA患者有17例(62.9%),10例无反应性;15例(55.6%)HLA-DR4/阳性RA患者抗HA308-317抗体阳性.在HLA.DR4/I表型阴性的RA患者中,T细胞对HA308.317多肽有反应性者10例(23.3%),无反应性者33例;25例(58.1%)患者抗HA308-317抗体阳性.HLA-DR4/1表型阳性组HA308-317特异性细胞增殖高于HLA-DR4/1表型阴性组(P＜0.01),但两组血清中HA308-317抗体水平差异无统计学意义(P＞0.05).结论 RA患者HA308-317特异性T细胞增殖与HLA-DR4/1表型有关,HA308-317抗体生成与HLA-DR4/l亚型无明显关系;HA308-317多肽可能通过诱导HLA-DR4/1特异性T细胞活化参与RA的发病.     

HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.     

甲状腺浸润T细胞活化与滤泡细胞DR抗原表达

用硷性磷酸酶抗硷性磷酸酶(APAAP)免疫细胞化学法,检测桥本甲状腺炎(HT)及其它甲状腺疾病甲状腺单个核细胞(TG-MNC)中四种 T 细胞活化抗原表达及甲状腺滤泡细胞(TFC)HLA-DR 表达,发现在 HT 与甲状腺肿的甲状腺中 T 细胞活化程度差异明显,而在 HT 与 Graves 病间差异则不明显。活化 T 细胞可攻入甲状腺滤泡;多种甲状腺病可出现 DR 抗原异常表达,但以 HT 为显著。认为 T 细胞活化与 TFC HLA-DR 抗原异常表达有关。     

夫妇HLA-DR抗原相容性与习惯性流产的关系

目的探讨夫妇HLA-DR抗原相容性和习惯性流产的关系。方法采集2007年8月—2009年8月在我院就诊的30对习惯性流产夫妇外周血,各5 ml,以同时期正常妊娠夫妇作为对照组,抽提样本基因组DNA,确定HLA-DR等位基因位点及其对应抗原,分析疾病组与对照组中抗原相容性分布是否具有差异。结果在检出的DR抗原中,两组抗原频率差别无统计学意义（P〉0.05）。疾病组中,有6对（20%）夫妇HLA-DR抗原零相容,18对（60%）夫妇一个抗原相容,6对（20%）夫妇两个抗原相容。对照组中,21对（70%）夫妇零相容,7对（23%）夫妇一个抗原相容,2对（7%）夫妇两个抗原相容。两组夫妇抗原相容性分布有显著性差异（P〈0.01）。一个抗原相容对于零抗原相容的相对危险度（RR）为9,两个抗原相容相对于零抗原相容的相对危险度（RR）为10.5。结论习惯性流产的发生与免疫失衡有关,夫妇双方HLA-DR抗原相容性增加,致母体对异体抗原识别不足,不能产生足够的封闭性抗体,胚胎遭排斥而产生流产。     

An in vitro approach to the kinetics of insulin antibodies in diabetic patients

The purpose of this study is to evaluate the binding behavior of plasma insulin antibodies (Iab) in diabetic patients, by the following parameters: Incubation time, temperature, buffer pH, and Iab titer. We investigated the plasma insulin binding patterns of 12 insulin-treated diabetic patients, and they were separated as higher titer group (Iab = 51.9 +/- 7.28, n = 6) and lower titer group (Iab = 14.88 +/- 4.75, n = 6). The procedure was: (1) plasma samples were deinsulinized by 0.12N HCL, dextran coated charcoal suspension and 0.12N NaOH. (2) I-125 monoiodoinsulin was used to prevent artifacts resulting from variability in ligand binding due to excessive iodination, (3) separation of free and bound insulin was accomplished by rapid precipitation of hormone-antibody complex with polyethylene glycol, and (4) decanting the supernatants and counting the pellets in the automatic gamma counter. The data were obtained as the condition of incubation time, temperature, buffer pH, and Iab titer. The results obtained by the Scatchard analysis indicated that high temperature (39 degrees C vs 37 degrees C) in vitro would increase the free insulin levels and decrease the low affinity binding capacity (Q2-Q1) of Iab in patients with high titer of Iab (greater than 40%), whereas this phenomenon is not observed in patients with low affinity binding sites of Iab in patients with low titers of insulin antibodies (less than 20%).     

慢性肾炎肾衰患者的HLA分型

作者应用标准微量淋巴细胞毒试验方法，对我国南方８０例肾小球肾炎所致慢性肾衰患者和５８０例正常人进行ＨＬＡ分型，结果发现：本病与ＨＬＡ－Ａ，Ｂ抗原无显著相关，而与ＨＬＡ－ＤＲ４抗原显著相关（Ｐ＜０．０５）。慢性肾炎肾衰患者的ＤＲ４抗原频率为４８％，正常对照则为１９．８％。推测我国南方慢性肾炎肾衰患者的ＤＲ４抗原高频率与该地区的原发笥ＩｇＡ肾病发病率高有关，具有ＤＲ４抗原的原发性ＩｇＡ肾病预后不良，该     

HLA-DRB1 ALLELES GENOTYPING IN PATIENTS WITH RHEUMATOID ARTHRITIS IN CHINESE

ＨＬＡ－ＤＲＢ１ＡＬＬＥＬＥＳＧＥＮＯＴＹＰＩＮＧＩＮＰＡＴＩＥＮＴＳＷＩＴＨＲＨＥＵＭＡＴＯＩＤＡＲＴＨＲＩＴＩＳＩＮＣＨＩＮＥＳＥＺｈａｏＹａｎ（赵岩）；ＤｏｎｇＹｉ（董怡）；ＺｈｕＸｉｌｉｎ（朱席林）ａｎｄＱｉｕＣｈａｎｇｃｈｕｎ（邱长春）（Ｎ...     

DR antigens and rheumatoid arthritis: a study of two populations

Thr prevalence of HLA-DR antigens was determined in a group of white patients with rheumatoid arthritis, similar patients originating from the Indian subcontinent, and corresponding controls. Rheumatoid arthritis was found to be highly associated with DR4 in the white patients but with DR1 in the Indian patients. These results raise the possibility that the DR antigens themselves do not play a part in increasing susceptibility to rheumatoid arthritis, but the locus for increased susceptibility is probably closely linked to the DR locus.     

广西壮族人群类风湿关节炎患者HLA-DR53、DR4基因及其与抗-CCP抗体的相关性研究

目的探讨广西壮族类风湿关节炎(RA)患者人类白细胞抗原(HLA)-DR53、DR4基因发生的频率数及其与抗-CCP抗体相关性。方法研究对象为49例RA患者及54例健康体检者,采用PCR-SSP法检测HLA-DR53、DR4基因;ELISA法检测抗-CCP抗体。结果 1DR4基因出现频率在RA患者与健康者相当(P>0.05)。2DR53基因出现频率在RA患者明显高于健康者(P<0.05)。3HLA-DR4基因阳性患者更易出现抗-CCP抗体阳性(P<0.05)。结论 1我区壮族人群DR4与RA的发病无相关。2DR4基因阳性RA患者更易出现抗-CCP抗体阳性。3DR53基因阳性RA者与抗-CCP抗体阳性无相关。     

Antinuclear antibodies and HLA class II alleles in Jamaican patients with systemic lupus erythematosus

OBJECTIVE: The relationship between human leukocyte antigens class II (HLA) and antinuclear antibodies was investigated in Jamaican patients with Systemic Lupus Erythematosus (SLE). METHODS: Samples of blood of 82 patients with SLE and 75 healthy controls were tested for antinuclear antibodies using the fluorescent antinuclear antibody (FANA) test, counterimmunoelectrophoresis (CIEP) and the Crithidia luciliae immunofluorescence test (CL-IFT). A DNA-based HLA typing method was used to determine the frequencies of alleles of HLA-DRB1, DRB3, DRB4 and DRB5 in patients and healthy controls. RESULTS: The FANA test was positive in all of the sera from patients with SLE. Anti-dsDNA antibodies were present in 49% (40/82), anti-Sm/RNP 44% (36/82) and anti-Ro/La 43% (35/82) of the sera from SLE patients. The frequency of HLA-DR4 was significantly lower in SLE patients than in healthy controls (2/82, 2% vs 15/75, 20%; RR = 0.12; p = 0.0004; CP = 0.005) but no other HLA-DRB1 SLE associations were found. A positive HLA-DR3 anti-Ro/La antibody association was found in the patients with SLE (9/21, 43% vs 5/55, 9%; odds ratio (OR) = 7.5; CP = 0.01). In contrast, possession of HLA-DR6 was negatively associated with the absence of anti-dsDNA antibodies (9/32, 28% vs 27/44, 61%; OR = 0.2; CP = 0.05). CONCLUSION: The HLA-DR6 allele is associated with the absence of antinuclear antibodies and HLA-DR3 with the presence of anti-Ro/La antibodies in Jamaican patients with SLE. However, these results and those of previous studies of Jamaican patients suggest that the HLA-DR3 association with the development of SLE reported in other populations might in fact reflect the association of HLA-DR3 with anti-Ro/La antibodies. Further investigations are needed to determine whether HLA-DRB antinuclear antibody associations define clinical subsets of SLE in Jamaican patients.     

HLA-DR typing in coeliac disease: evidence for genetic heterogeneity

Sixty nine propositi from a family study of coeliac disease were typed for HLA-DR antigens. Sixty three (91%) were found to carry the antigen DR3, which was a significantly greater proportion (p = 9.6 X 10(-24] than among the 168 controls (26%). Concurrently 42 children with the disease were DR typed. Not only was the frequency of DR3 significantly increased in these patients (86% versus 26% in controls; p = 3.1 X 10(-12] but so also was the frequency of DR7 (patients 60%, controls 29%; p = 5.8 X 10(-4]. When those propositi whose coeliac disease presented before the age of 20 were combined with the childhood coeliac group and a comparison made between these patients and the remainder of the propositi, all of whom presented when they were older than 20, the childhood onset group had a significant excess of DR7 (p = 2.2 X 10(-3] and a significant deficiency of DR2 (p = 3.5 X 10(-3]. These findings indicate that childhood coeliac disease and adult coeliac disease are genetically heterogeneous.     

Triad of markers for identifying children at high risk of developing insulin-dependent diabetes mellitus

A longitudinal investigation was conducted from 1977 to 1984 on 178 families in which one or more of the children had insulin-dependent diabetes mellitus. Of 351 nondiabetic sibs followed up for an average of 54 months, ten have, thus far, become diabetic. Eight sibs were HLA identical to their diabetic proband and nine had HLA-DR3 and/or HLA-DR4. Islet cell surface antibody and islet cell cytoplasmic antibody were found from two to 74 months before the onset of clinical diabetes in 100% and 90%, respectively, of the children. A decrease in insulin secretion was observed in all of these children on entry into the study and was detected in the absence of elevated plasma glucose concentrations. The data suggest that the triad of HLA identity, pancreatic islet cell antibodies, and depressed insulin secretion identifies those sibs who are at high risk of developing insulin-dependent diabetes mellitus.     

HLA antigens and acetylcholine receptor antibodies in penicillamine induced myasthenia gravis

Antibodies to the acetylcholine receptor and HLA antigens have been studied in patients with myasthenia gravis occurring in association with penicillamine treatment. The properties of the antiacetylcholine receptor in these patients differed from those in patients with idiopathic myasthenia gravis in terms of specificity and affinity. These patients had an increased prevalence of HLA Bw35 and DR1 compared to controls and a decreased frequency of B8 and DR3 compared to patients with idiopathic myasthenia gravis. Likewise, they had a decreased frequency of DR4 compared to patients with rheumatoid arthritis. These data provide supportive evidence for a role for penicillamine in the induction of myasthenia gravis in genetically predisposed individuals.     

Role of Molecular Typing in Live Related Donor Renal Transplantation

In renal transplantation, a good HLA-DR match is associated with higher success rate of graft outcome. It is particularly so In high risk recipients. Serological HLA-DR typing is not always easy due to a number of technical problems. In view of this, a comparison of serological and molecular typing was done in our institutions. A total of 64 live related donor patients of renal transplantation were studied. Serological typing was done by conventional methods. Molecular HLA class II typing was done by polymerase chain reaction (PCR) based sequence specific oligonucleotide probe (SSOP) hybridization technique. An overall discrepancy of 19.5% was observed in the DR typing obtained by serology and PCR-SSOP of all the recipients and donors. 14.5% of cases showed discrepancy in the results of only one DR antigen. Serological typing failure was seen in 10.9% of total cases. In 19.5% cases, only one DR antigen was assigned by PCR-SSOP as compared to two antigens by serological methods. Maximum number of discrepancies were seen in DR 2 antigens. There was no appreciable difference of graft survival shown in the patients typed by both methods. However, higher incidence of acute graft rejection episodes were seen in patients with 1 antigen mismatch as compared to zero mismatch. It is concluded that HLA-DR typing should be carried out by molecular methods as these have been found to be more specific and accurate.Key Words: HLA-DR, Molecular typing     

HLA—Ⅱ血清学分型与微量SSP法基因分型的比较分析

目的 验证微量序列特异性引物（SSP）技术进行HLA－Ⅱ类移植配型的准确性并探讨血清学分型错误发生的原因。方法 采用聚合酶链反应结合微量SSP技术（简称微量PCR－SSP法）以及单克隆抗体血清学分型技术对血清样品进行HLA分型并比较其结果。结果 （1）微量PCR－SSP法检测的110例样本中，99例检出HLA－DR的396个等位基因、11例检出HLA－DQ的22个等位基因，检出10％的单倍型个体；（2）两种方法对比研究发现单克隆抗体血清学分型检出错误和漏检率较高，其误差在DR和DQ分别为38．81％和50．75％；（3）错误发生和易混淆的抗原为：DR15／16、11／12、13／14、8、12和DQ5／6、8／9。结论 微量SSP法可以准确检定血清学易漏检和发生错误的抗原等位基因。     

沈阳地区汉族人群中HLA—DR、DQ抗原多态性分析

1.本文报道了HLA—DR、DQ抗原在沈阳汉族人群中的分布,HLA—DR基因频率为0.8132,尚有空白0.1868,HLA—DQ基因频率为0.7964,尚有空白0.2036。说明沈阳地区汉族人群无论HLA—DR或HLA—DQ均有新的抗原未被发现。2.HLA—DR1明显高于上海、湖北及四川;HLA—DR 3明显低于湖北,略低于上海;HLA—DR 4明显低于湖北,HLA—DR 7明显低于上海,HLA—DRw9明显低于上海、四川。HLA—DQw 3明显低于四川。3.本文首次在中国沈阳汉族人群中检测到HLA—DQw 2、DOwa、TA10。     

HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins

Background Because of the pivotal role of the human leukocyte antigen （HLA） class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin. Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies （4 major and 4 minor antigenic determinants） in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some （113 patients and 87 healthy control subjects） were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction. Results Compared with control subjects, a sign/ficantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria （P = 0.011; P = 0.019; P = 0.005 respectively）. Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group （P = 0.024; P = 0.038; P = 0.038）. A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not （X^2 = 5.134, P = 0.023）, and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl （PVA, X^2 = 4.057, P = 0.044）. Conclusion I-ILA-DRB gene may be involved in allergy to pcnicillins through modulating spvcific serum IgE to penicillins.     

严格血糖控制对危重症炎症与免疫状态的影响

目的了解创伤、感染等应激后重症病人血清CRP(C反应蛋白)、IL-6(白细胞介素-6)、MIF(巨噬细胞移动抑制因子)及外周血单核细胞人类白细胞抗原(HLA-DR)的变化及其与应激性高血糖的相互关系;探讨强化胰岛素治疗对重症病人体内炎症反应与免疫状态的影响。方法33例收住SICU的重症病人分为3组:血糖控制1组(目标血糖4.44~6.11mmol/L),血糖控制2组(目标血糖6.66~8.33mmol/L),对照组(目标血糖9.99~11.10mmol/L),入选后第1、4、7天测定外周血单核细胞HLA-DR及血清IL-6、MIF、CRP的动态变化。结果3组病人血清CRP、IL-6、MIF均明显升高,CRP与血糖水平呈正相关(P<0.05);外周血单核细胞HLA-DR降低,与血糖水平呈负相关(P<0.05)。强化胰岛素治疗后,血糖控制1组与对照组相比,血清CRP、IL-6在第7天显著下降(P<0.05),血清MIF的下降与对照组差异无统计学意义(P>0.05),而HLA-DR明显高于同期对照组水平(P<0.05)。结论强化胰岛素治疗将血糖控制于正常水平更有助于增加外周血单核细胞表面HLA-DR的表达,下调应激后重症病人机体内炎症反应状态。     

具有鼻咽癌相关抗原内影像的抗独特型抗体研究

用抗人鼻咽癌单抗FC2,HNL5(Ab1)分别免疫Balb／C小鼠,制备了两株抗独特型抗体2H4和5D3(Ab2)。结果显示：2H4和5D3分别与FC2和HNL5特异性结合,抑制Ab1与靶细胞的反应,诱导产生能与相应Ab1竞争结合靶抗原的抗抗独特型抗体(Ab3);并能诱发特异性迟发型超敏反应(DTH)和细胞增殖反应。表明2H4和5D3具有鼻咽癌相关抗原的内影像(Ab2β),能模拟鼻咽癌相关抗原诱导体液和细胞免疫反应。