华南地区汉族胰岛素依赖型糖尿病易感性与HLA—DR9相关性的初步 …

应用套式ＰＣＲ检测华南地区汉族６４例Ｉ型糖尿病病人（ＩＤＤＭ）（包括１５岁前起病组１７例，１５￣３０岁起病组３０例和３０岁后起病组１７例）和７２例健康对照者的ＨＬＡ－ＤＲ９等位基因。结果：ＩＤＤＭ组和对照组ＨＬＡ－ＤＲ９等位基因频率分别为４６．９％和３３．３％，无显著性差异（Ｐ〉０．０５）。１５岁前起病组、１５￣３０岁起病组和３０岁后起病组中ＨＬＡ－ＤＲ９频率分别为５８．８％、４６．７％和３５．３     

血小板输注与HLA抗体的临床意义

血小板输注与ＨＬＡ抗体的临床意义李敬兰金宗骧赵纯平杨杰坤曹金霓我们检测６６例长期输血小板的急性白血病（ＡＬ），再生障碍性贫血（ＡＡ）的同种抗体（ＨＬＡ抗体），并观察部分抗体阳性患者血小板交叉配型输血的临床效果。一、材料与方法１．观察对象、血小板来源与...     

大动脉炎易感性与HLA-DRB基因相关性研究

目的 探讨大动脉炎易感性与ＨＬＡ－ＤＲＢ等位基因频率的相关性。方法 以８４例汉族大动脉炎患和１０２例健康汉族人（对照组）为研究对象,采用ＰＣＲ－ＳＳＰ及ＰＣＲ－ＲＦＬＰ方法进行ＨＬＡ－ＤＲＢ等位基因分型,比较其等位基因频率在大动脉炎患与对照组之间的差异。结果 ＨＬＡ－ＤＲ４、ＤＲ７等位基因频率在大动脉炎组显高于对照组（３８．１％比１５．７％,Ｐ〈０．０１,ＲＲ＝２．４３;４７．６％比１０．８     

HLA—DRB1等位基因与我国北方类风湿关节炎的关系

为了观察ＨＬＡ－ＤＲＢ１等位基因在类风湿关节炎（ＲＡ）临床及发病中的作用，对８６例ＲＡ患者和１０６名正常对照的ＨＬＡ－ＤＲＢ１等位基因进行分型。用序列特异性引物体外基因扩增法测定ＨＬＡ－ＤＲ特异性，用序列特异性寡核苷酸探针进行ＨＬＡ－ＤＲ４亚型的测定。并根据ＨＬＡ－ＤＲＢ１等位基因的分型结果分析ＲＡ的临床表现和血清学特点及其与ＲＡ患者预后的关系。结果表明：同对照组相比，ＲＡ患者中ＨＬＡ－ＤＲ４基因频率明显增高（４８．８％比１７．９％，Ｐ＜０．００１），而ＨＬＡ－ＤＲ５基因频率降低（１６．３％比２７．４％，Ｐ＝０．０６）。ＤＲ４阳性ＲＡ中主要的ＤＲ４亚型为ＨＬＡ－ＤＲＢ１＊０４０５（６１．９％比２１．１％，Ｐ＜０．０１）。在ＤＲ４阳性和ＤＲ４阴性两组患者中，其发病年龄、病程和关节外表现无明显差异，但ＤＲ４阳性组的类风湿因子阳性率高于ＤＲ４阴性组（Ｐ＜０．０５），并且ＤＲ４阳性的ＲＡ患者腕和（或）指关节Ｘ线片分期明显重于ＤＲ４阴性者（Ｐ＜０．０５）。本研究结果表明，我国北方ＲＡ患者和ＨＬＡ－ＤＲ４基因明显相关，其主要亚型为ＨＬＡ－ＤＲＢ１＊０４０５。ＲＡ患者ＨＬＡ－ＤＲ４基因的检测可作为一项有用的预后判断指标。     

新生儿滤纸血斑TSH检测TR—IFMA,IRMA,ELISA的对比研究

对碘缺乏病病区和非病区新生儿脐带滤纸血斑同时利用三种方法检测ＴＳＨ值，结果表明ＩＲＭＡ值＞ＴＲ－ＩＦＭＡ值＞ＥＬＩＳＡ值，三者相关非常显著，相关系数分别是ＴＲ－ＩＦＭＡ与ＥＬＩＳＡ为０．８３８、ＥＬＩＳＡ与ＩＲＭＡ为０．８３５、ＩＲＭＡ与ＴＲ－ＩＦＭＡ为０．７７７。５ｍＵ／Ｌ以下所占百分率ＥＬＩＳＡ为７６．９％、ＴＲ－ＩＦＭＡ为６４．７％、ＩＲＭＡ为４４．８％。经多年补碘的病区与非病区ＴＳＨ值分布频率基本相似。认为三种方法均可用于碘缺乏病监测，但ＩＲＭＡ值偏高，可根据回归方程ＴＲ－ＩＦＭＡ、ＥＩＡ值进行换算。     

HLA—DR4基因检测在类风湿关节炎诊治中的意义探讨

为了研究ＨＬＡ－ＤＲ４基因检测在类风湿关节为诊治中的意义，对５０例类风湿关节炎患者进行了ＨＬＡ－ＤＲ４的（ＰＣＲ－ＳＳＰ方法）检测，同时结合患者的临床表现和实验室指标进行分析。结果显示：ＨＬＡ－ＤＲ４阳性者３１例（阳性率为６２％）；比较ＨＬＡ－ＤＲ４阳性和阴性两组患者其他指数，可见，ＩＨＬＡ－ＤＲ４阳性组的关节疼痛指数、ＥＳＲ、类风湿因子（ＲＦ）滴度均明显高于ＨＬＡ－ＤＲ４阴性组（Ｐ值分别〈０．０     

自身免疫甲状腺疾病患者淋巴细胞亚群和自身抗体的临床研究

作者报告１５０例自身免疫甲状腺疾病和２５例亚甲炎患者淋巴细胞亚群、甲状腺自身抗体和甲状腺激素测定结果。ＧＤ和ＨＴ未治组ＣＤ８＋、ＣＤ３＋下降、ＣＤ＋４／ＣＤ＋８比值和ＣＤ＋２０升高（Ｐ均＜０．０１）。ＧＤ未治组ＴＲＡｂ、ＴＭＡ和ＴＧＡ阳性率分别为９０．０％、６１．１％和５７．Ｏ％；ＨＴ未治组为２０．０％、８５．０％和７０．０％。亚甲炎组变化不明显。ＧＤ缓解组以上各指标均转向正常范围。ＧＤ未治组ＣＤ８＋与ＴＲＡｂ呈明显负相关，ＣＤ２０＋与ＴＲＡｂ呈显著正相关。ＣＤ８＋、ＣＤ２０＋与ＴＲＡｂ的检测是判断Ｇｒａｖｅｓ病发病机制及治疗效果和预后的可靠指标。     

HLAⅡ类抗原与病毒性心肌炎相关性的研究

目的：探讨人白细胞Ⅱ类抗原（ＨＬＡⅡ）与病毒性心肌炎（ＶＭＣ）的相关性。方法：用ＨＬＡ单克隆抗性体以微量淋巴细胞毒性试验调查３２例福建地区ＶＭＣ患者ＨＬＡ－ＤＲ和ＤＱ位点共２０个特异性抗原频率,并与４３例本地区政党人加以对照。结果：ＶＭＣ病人与ＨＬＡ－ＤＱ７（ＲＲ＝７．６００,ＰＣ＝０．００２）和ＤＱ２（ＲＲ＝０．１６１,ＰＣ＝０．００２）抗原分别为显著正、负相关结论：ＶＭＣ与ＨＬＡⅡ类抗原异常表     

广东汉人HLA—DRB1基因的PCR—SSP定型分析及其对风湿热遗传 …

目的：研究了ＨＬＡ－ＤＲＢ１基因对风湿热的遗传易感性，方法；用ＰＣＲ－ＳＳＰ方法对广东地区５１例风湿热患者和１０２位正常人的ＨＬＡ－ＤＲＢ１基因进行定型分析且探讨ＨＬＡ－ＤＲＢ１等位基因与风湿热的相关性。结果：风湿热患者ＨＬ－ＡＤＲＢ１等位基因分布异常喏上素ＤＲＢ１＊０３０１基因频率为２３．３％，而正常人仅为６．５９％。     

银屑病关节炎临床特点及与HLA—B27的相关性研究

目的 分析银屑病关节炎（ＰＡ）的临床特点及与ＨＬＡ－Ｂ２７的相关性。方法 选５５例住院患者，总结分析其皮疹和关节炎，关节外表现，Ｘ线特征及骶髂关节炎与ＨＬＡ－Ｂ２７的关系。结果 ３６例皮疹先于关节炎出现，１３例关节炎在先，６例同时发生。３８例有指甲改变。手足小关节最易受累，共计４５例，占８１．８％，２８例（６２．２％）伴远端指间关节（ＤＩＰ）受累。２８例有关节外表现。２０例有手足小关节Ｘ线破坏征，     

Pilot study of HLA alloimmunization after transfusion with pre-storage leucodepleted blood products in aplastic anaemia

We have performed a pilot study to examine the incidence of alloimmunization using pre-storage leucocyte-depleted blood products (PLDP) in 16 previously transfused aplastic anaemia (AA) patients with no detectable HLA antibodies. A further eight AA patients with HLA antibodies received HLA-matched PLDP. Leucodepleted apheresed platelets were obtained using either Cobe spectra or Haemonetics system with an integral pall filter. Pall BPF4 filters were used for red cell preparation. Patients' sera were tested for HLA antibodies using lymphocytotoxicity (LCT). Patients who were HLA antibody negative by LCT at study entry were further tested with enzyme-linked immunoassay (ELISA). Out of 16 patients, two (12%) formed anti-HLA antibodies with a median follow-up of 9 months (range 1–15), but did not display platelet refractoriness to random donor platelets. Two patients were inadvertently transfused with non-leucodepleted blood products when later referred back to their local hospital. Both subsequently demonstrated HLA antibodies by LCT and became platelet refractory. These results contrast with a 50% incidence of HLA alloimmunization in a control group of AA patients transfused prior to this study with non-PLDP. HLA antibodies could no longer be detected by LCT in follow-up of three out of eight patients with HLA antibodies at study entry. Only one patient experienced non-haemolytic febrile transfusion reactions (NHFTR). We conclude that PLDP reduce the risk of alloimmunization even in previously transfused AA patients, PLDP are associated with a low incidence of NHFTR, and all new AA patients should receive PLDP from diagnosis.     

Red blood cell transfusions are associated with HLA class I but not H‐Y alloantibodies in children with sickle cell disease

Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion‐related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion‐related alloimmunization to minor histocompatibility antigens (mHA), such as H‐Y antigens, has not been clinically characterized. We conducted a cross‐sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H‐Y antigens and to HLA class I and class II. Few patients had H‐Y antibodies, with no significant differences in the prevalence of any H‐Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P = 0·046; class II: 7% vs. 8%, P = 0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1–22·3). These results are consistent with immunological responder and non‐responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion‐related alloimmunization.     

Evaluation of the quality of HLA antibodies in placental blood

Two groups of blood samples, placental blood and female donor blood, were shown to have a frequency of 16.4 and 1.5% of anti-human leucocyte antigen (HLA) antibodies respectively. The specificities and qualities of these antibodies were further characterized by their relative coefficient (r) values and strength indices (SIs). Most had an r value of approximately one, but their SIs varied from 41 to 100%. Among these two groups, nine samples gave very strong and definite results (r = 1 and SI = 100%). Data analysis revealed that the qualities of the two groups were comparable. However, the antibody positive rate was higher in placental blood samples than that in donor blood samples.     

Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation

The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)‐alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo‐HSCT) are unknown. We studied HLA‐alloantibodies in a cohort of 16 patients (eight HLA‐alloimmunized with pre‐transplant histories of PTR and eight non‐alloimmunized controls) undergoing Allo‐HSCT using fludarabine/cyclophosphamide‐based RIC. Pre‐ and post‐transplant serum samples were analysed for HLA‐antibodies and compared to myeloid, T‐cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA‐antibodies persisted post‐transplant correlated strongly with pre‐transplant HLA‐antibody mean fluorescence intensity (MFI) and PRA levels (Spearman's rank correlation = 0·954 (P = 0·0048) and 0·865 (P = 0·0083) respectively). Pre‐transplant MFI >10 000 was associated with post‐transplant HLA antibody persistence >100 d (P = 0·029). HLA‐antibodies persisted ≥100 d in 3/8 patients despite recipient chimaerism being undetectable in all lympho‐haematopoietic lineages including plasma cells. Post‐transplant de‐novo HLA‐antibodies developed in three control patients with two developing PTR; the donors for two of these patients demonstrated pre‐existing HLA‐antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA‐antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post‐transplant PTR as a consequence of donor–derived HLA alloimmunization before recommendations on donor HLA‐antibody screening can be made.     

Clinical and HLA phenotypes of type 1 autoimmune hepatitis in North American patients outside DR3 and DR4.

AIMS: To determine the clinical phenotype and outcome of patients with definite type 1 autoimmune hepatitis, who lack human leukocyte antigen (HLA) DR3 and DR4, and to assess the importance of HLA DR7 and DR13. METHODS: Two hundred and seven adult patients were typed for DR3, DR4, DR7, and DR13 by DNA-based techniques. One hundred and two blood donors constituted a normal population. RESULTS: Twenty-six patients lacked DR3 and DR4 (13%). Treatment failure occurred more commonly in these individuals than in the 68 patients with DR4 (20% vs. 3%, P = 0.03), and relapse after drug withdrawal was less frequent than in the 84 patients with DR3 (55% vs. 87%, P = 0.03). HLA DR13 occurred more often than in those with DR3 (54% vs. 15%, P = 0.0002) or DR4 (54% vs. 12%, P = 0.00005), and it was more frequent than in normal adults (54% vs. 22%, P = 0.003), including those without DR3 or DR4 (54% vs. 27%, P = 0.03). HLA DR7 was not associated with susceptibility or outcome. CONCLUSIONS: White North American patients who lack DR3 and DR4 respond differently to corticosteroid treatment than patients with classical HLA phenotypes. HLA DR13 is common in these adult patients, and it may affect treatment outcome.     

Coxsackie B4 viral infection,anti-islet immunity and immunogenetics in insulin-dependent diabetes mellitus

Summary The interrelationship between Coxsackie B₄ (CB4) virus antibodies, islet-cell antibodies and HLA B8 was studied in 67 patients with juvenile-onset diabetes mellitus (JOD). In 41 JOD patients (61%) CB4 antibodies (>1:4) were found. A high prevalence (69%) of significant CB4 antibody titers (>1:64) was observed in patients with age at onset between 11 and 20 years compared with those with age at onset below or over that age-range (27% and 33%, respectively). Islet-cell antibodies (ICA) could be detected only in 11 JOD patients, which is probably due to the relatively long mean duration of disease. However, 8 of them presented with significant CB4 antibody production. Although no correlation between CB4 antibodies and the JOD-associated HLA-antigens (B8, Bw15, Cw3 and B7) could be detected in the entire group of JOD patients, a close association between ICA persistence and HLA B8 was found. Furthermore, in the ICA-positive, moderate or high CB4 antibody titers were prevalent. Thus, the present data point to a possible interrelationship between CB4 virus antibodies, persistent ICA production and HLA B8 in a minor proportion of JOD patients. However, it seems premature to assume direct implication of these factors in the pathogenesis of JOD. National Blood Group Reference Laboratory (WHO), National Tissue Typing Reference Laboratory (Council of Europe).     

High titre of antiglutamic acid decarboxylase autoantibody is a strong predictor of the development of thyroid autoimmunity in patients with type 1 diabetes and latent autoimmune diabetes in adults

Objective Type 1 diabetes mellitus (T1DM) is frequently associated with autoimmune thyroid diseases (AITD), but little is known about the risk of AITD in latent autoimmune diabetes in adults (LADA). We evaluated the genetic and immunological factors involved in the development of thyroid autoimmunity in patients with LADA and T1DM. Patients and measurements One hundred and ninety T1DM and 135 LADA patients were recruited in the study. Thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), glutamic acid decarboxylase antibody (GADA) and thyroid function were measured. The cytotoxic‐lymphocyte‐associated antigen‐4 (CTLA‐4) +49A/G and CT60 polymorphisms and the human leucocyte antigen (HLA)‐DQA1‐DQB1 genotype were determined. Results The prevalence of thyroid antibodies (TGAb and/or TPOAb) and thyroid dysfunction was 27·4% and 9·5% in patients with T1DM, and 21·5% and 11·1% in patients with LADA. Thyroid‐antibody‐positive T1DM patients had higher frequencies of GADA and HLA‐DQA1*03‐DQB1*0401 haplotypes than thyroid‐antibody negatives (P < 0·05). Thyroid‐antibody‐positive LADA patients had higher GADA titre, lower C‐peptide levels and higher frequencies of HLA‐DQA1*03‐DQB1*0401 haplotypes (P < 0·05). The CTLA‐4 +49A/G and CT60 polymorphism was associated with T1DM complicated with thyroid autoimmunity (OR = 2·33 and 2·54). Logistic regression revealed that only high‐titre GADA was associated with development of thyroid autoimmunity in patients with T1DM and LADA (OR = 3·50 and 3·10, respectively), and the presence of thyroid antibody predicted high risk for thyroid dysfunction in patients with T1DM and LADA (OR = 9·25 and 10·70, respectively). Conclusion Regular screening of thyroid antibody and function are recommended, especially in patients with T1DM and LADA with high GADA titre.     

Analysis of HLA‐DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA‐DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

Aims: Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA‐DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1–452‐month observation period. Results: Anti‐gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20–850.1) and anti‐centromere antibodies (OR, 2.36, 95% CI, 1.28–4.35) were significant risk factors for jaundice‐ and nonjaundice‐type progression, respectively. HLA‐DRB1*0405 and *0803 predisposed patients to anti‐gp210 (OR, 1.61, 95% CI, 1.08–2.39) and anti‐centromere (OR, 2.30, 95% CI, 1.41–3.73) antibody production, respectively. HLA‐DRB1*1502 and *0901 patients were predisposed to nonjaundice‐type progression (OR, 1.98, 95% CI, 1.13–3.40 and OR, 1.78, 95% CI, 1.02–3.03), while HLA‐DRB1*0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48–3.41 and OR, 1.53, 95% CI, 1.11–2.11, respectively). Stratifying patients by HLA‐DRB1 alleles revealed that anti‐gp210 antibodies was a strong risk factor, regardless of the HLA‐DRB1 alleles for jaundice‐type progression, while anti‐centromere antibodies was a significant risk factor for nonjaundice‐type progression in patients with HLA‐DRB1*0405 (OR, 6.89, 95% CI, 2.18–26.56) and ‐DRB1*0803 (OR, 5.42, 95% CI, 1.47–24.62) but not other HLA‐DRB1 alleles. Conclusions: HLA‐DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.     

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis

AIM To evaluate hepatitis B virus(HBV) vaccine response and correlation with human leukocyte antigens(HLA) and/or gluten intake in celiac patients at diagnosis.METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania(Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody(anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0to 5.5 years(48.9%, group A); 16 aged between 5.5 and 9.5 years(30.61%, group B); 9 aged between 9.5 and 17 years(18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups(P 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes(homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences(P 0.05).CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.