Major histocompatibility complex class II (DRB1*, DQA1*, and DQB1*) and DRB1*04 subtypes' associations of Hashimoto's thyroiditis in a Greek population

Hashimoto's thyroiditis (HT) is an autoimmune disease resulting from complex interactions between genetic and environmental factors. The disease is associated with certain human leukocyte antigen (HLA) class II alleles in various populations. We aimed to determine in this study, for the first time in a Greek population, the association of HLA-DRB1*, -DQA1*, and -DQB1* alleles with HT. HLA-DRB1*, -DQA1*, and -DQB1* alleles' and -DRB1*04 subtypes' distribution was evaluated in 125 patients with HT and in 500 healthy control individuals by using a DNA-based sequence-specific primer method. Chi^_squared tests and Bonferroni correction method were applied in the statistical analysis of the data. Significantly higher frequency of DRB1*04 (24.8% vs 7.7%, P  < 0.0001) was observed in HT patients, while HLA-DRB1*07 was significantly decreased (2.8% vs 7.9%, P  < 0.05). HLA-DRB1*04 subtyping showed a significant increase of DRB1*0405 (21% vs 7.8%, P  < 0.0001) in HT patients. Also significant high frequencies of DQB1*0201 (14.8% vs 8.2%, P  < 0.001), DQB1*0302 (18.8% vs 7.0%, P  < 0.0001), and DQA1*0301 (25.6% vs 7.8%, P  < 0.0001) were recorded in the patient group. Conducting the first research of this kind in a Greek population, our study tries to provide an evaluation of the prevalence of HT relating to HLA-DRB1*0405, and we report a relative risk of 2.7 for HT in a Greek population.     

HLA-DRB1基因与湘西土家族人群肺结核的易感性分析

目的：探讨HLA-DRB1基因多态性与湘西土家族人群肺结核的遗传关联性。方法：用病例与对照的研究方法，采用聚合酶链反应-序列特异性引物（PCR-SSP）技术，对69例湘西土家族人群肺结核患者和100例湘西土家族人群健康对照者HLA-DRB1等位基因进行分析。结果：与对照组相比，PTB病例组的DRB109基因频率增高（63．7％比14％Pc〈0．0001RR=10．81），而DRB111基因频率显著低于对照组（11．6％比29％Pc〈0．05）。结论：HLA-DRBI09可能是湘西土家族人群肺结核的易感基因，HLA—DRB111可能为保护基因。     

体外循环致炎与抗炎反应免疫指标的动态观察

目的探讨体外循环(CPB)导致全身炎症反应时致炎因子与抗炎因子的变化规律以及与机体免疫功能的关系,为临床防治全身炎症反应综合征(SIRS)提供实验依据。方法选取心内直视手术患者30例,用流式细胞仪测定单核细胞及淋巴细胞人类白细胞表面抗原-DR(HLA-DR)的表达,ELISA法测定血浆肿瘤坏死因子-α(TNF-α)和白介素-10(IL-10)浓度。结果CPB在导致炎症介质TNF-α升高的同时抗炎介质IL-10也随之升高,二者峰值出现的时间有一定差异,二者峰值呈正相关(r=0.698,P<0.01),CPB导致单核细胞HLA-DR表达下降,其随时间的变化趋势与IL-10相反。单核细胞HLA-DR最低值与CPB时间呈负相关(r=-0.489,P<0.05)。结论CPB导致炎症反应的同时抗炎反应也相继发生,炎症反应越强烈,抗炎反应也越强烈,机体免疫功能受损越为严重。CPB对机体的损伤是炎症反应与抗炎反应共同作用的结果。拮抗致炎因子的同时提高机体免疫功能维持致炎因子与抗炎因子平衡是治疗SIRS的新思路。     

类风湿关节炎患者外周血和关节滑膜液淋巴细胞CD25、HLA-DR的表达及意义

目的研究类风湿关节炎(rheumatoid arthritis,RA)患者外周血和关节滑膜液淋巴细胞CD25、HLA-DR的表达,探讨其在RA致病中的作用.方法采用流式细胞仪检测RA患者外周血和关节滑膜液淋巴细胞CD25、HLA-DR的表达,并设立正常对照组.结果RA患者外周血表达CD25的T淋巴细胞和B淋巴细胞,与正常对照组相比明显增多(P<0.01);关节滑膜液表达CD25的B淋巴细胞和表达HLA-DR的T淋巴细胞和B淋巴细胞,与正常对照组相比亦明显增多(P<0.01).结论外周血和关节滑膜液淋巴细胞CD25、HIA-DR的表达增高,在RA发病机制中起着重要的作用.     

围手术期应用西米替丁对结直肠癌TIL浸润及HLA-DR表达的影响

目的研究表明西米替丁(CIM)能增强胃肠癌患者机体的免疫力,本实验探讨了CIM对结直肠癌(CRC)肿瘤浸润淋巴细胞(TIL) 及肿瘤间质细胞HLA-DR表达的影响,以了解CIM在CRC局部免疫中的作用。方法将49例CRC随机分为治疗组与对照组,治疗组25例术前1周开始口服CIM；对照组进行常规治疗,不服用CIM；手术前后比较肿瘤间质TIL浸润程度及HLA-DR表达的变化。结果 CIM治疗组手术前后TIL的明显反应,由治疗前的32％(8／25)上升到治疗后的76％(19／25),差别有显著性(P＜0.005)；而对照组仅由治疗前的25％(6／24)上升至33％(8／24),无显著统计学差异。治疗组HLA-DR的高表达由治疗前的36％(9／25)上升到治疗后的72％(18／25),有显著差异性,而对照组由41.7％(10／24)上升至45.8％(11／24),无显著差异(P＞0.50)。结论术前应用CIM能增加CRC患者肿瘤组织TIL的浸润及增强间质细胞HLA-DR的表达,表明CIM能增加CRC患者的局部抗肿瘤免疫力。     

肾脏HLA－DR抗原表达在肾移植中的意义

应用免疫酶标技术对４７例异体肾移植患者的９５例次肾活检标本进行ＨＬＡ－ＤＲ抗原检测，同时做光镜、电镜、免疫病理检查及淋巴细胞亚群的研究。结果显示，肾移植后肾近曲小管上皮细胞的ＤＲ抗原表达增加，肾小球的ＤＲ表达减少；急、慢性排斥反应与急性肾小管坏死时，肾小管及肾间质的ＤＲ抗原表达均明显增加；环孢素中毒时，肾单位的ＤＲ抗原表达正常，肾间质的ＤＲ抗原表达增加。肾脏ＨＬＡＤＲ抗原表达在肾移植后的变化用于排斥反应的诊断、鉴别诊断、判断预后及治疗决策具有重要意义。     

Familial hereditary thrombocytopenia and HLA

Three generations of a Jewish family with hereditary thrombocytopenia (HT) are described. The disease was manifested clinically by mild bleeding tendency since infancy. Circumcision, however, did not result in excessive bleeding. HLA study in this family indicated that the HT locus is not linked to HLA.     

Comparison of membrane proteins of Burkitt's lymphoma and EBV-transformed B lymphoblast cell lines and of Con A-activated T lymphocytes and T lymphoblast cell lines.

The aim of this study was to examine the heterogeneity of membrane proteins of several B and T lymphoblast cell lines and activated normal T lymphocytes using SDS gel electrophoresis of [³⁵S]methionine metabolically labeled cells. In part, we hoped to test the hypothesis that human lymphocytic malignancies are “frozen” representatives of various stages in the differentiation paths of normal lymphoid cells. The membrane protein patterns of Burkitt's lymphoma cell lines were very similar to each other and to those of EBV-transformed B lymphoblastoid cell lines from healthy persons. The American Burkitt's lymphoma cell line Ramos lacked p29, 34 (HLA-DR) antigen, as was confirmed with immunoprecipitation studies of this complex and of p44, 12 (HLA-A, and -B antigens and β₂-microglobulin) from each of the cell lines. Heterogeneity in the electrophoretic mobility of HLA-DR antigen was apparent, reflecting size or charge variations. Small degrees of membrane protein heterogeneity among the T lymphoblast cultured cell lines was also evident. Proteins of mol. wt 90,000, 75,000, 18,000 and 16,000 were more heavily labeled on some cell lines than on others. This heterogeneity is consistent with the hypothesis that these tumors might be derived from cells of varying maturational stages or from different subsets of T lymphocytes. In contrast to the T lymphoblast lines, Con A-activated T lymphocytes on each successive day of stimulation expressed dramatically different membrane proteins. Proteins of mol. wt 30,000 and 36,000 were found on day 2 cells; mol. wt 55,000 proteins were dominant on days 1, 2 and 3; a group of proteins of mol. wt about 120,000 was present on cells surviving a lytic process on day 4. Although many proteins were shared between Con A blasts and cultured T cell lines, the absence from the cultured lines of proteins which were dominantly synthesized by mitogen-activated lymphoblasts was consistent with the view that long-term cultured lymphoblasts represent a more primitive, undifferentiated, immature T-cell population, while the changes seen with Con A activation represent metabolically controlled changes consequent to activation of one or more subsets of mature T cells. While many proteins were shared among membrane proteins of T lymphoid tumors and mitogen-activated, normal T lymphocytes, the differences were so striking that simple parallelisms between these lymphoid tumors and activated sets of normal lymphocytes could not be proposed.     

The increase of antiglomerular basement membrane antibody following pauci-immune-type crescentic glomerulonephritis

A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8mg/dl) and creatinine (3.4mg/dl) suggested rapidly progressive glomerulonephritis. The serological study revealed all negative results for rheumatoid factor, antinuclear antibody, serum cryoglobulins, MPO-ANCA, PR3-ANCA, and anti-streptolysin O. Antiglomerular basement membrane (GBM) antibody, as assessed by ELISA, was 11EU (normal, <10). Kidney biopsy on the eighth hospital day demonstrated pauci-immune-type crescentic glomerulonephritis without ANCA. Methylprednisolone pulse therapy (500mg/day, 3 days) and 45mg/day prednisolone orally were started. At 3 weeks after kidney biopsy, the anti-GBM antibody value increased from 11EU/ml to 116EU/ml, and MPO and PR3-ANCA were still negative. HLA type was DR8 and DR 15(2), with a genotype of HLA-DRB1*08021 and HLA-DRB1*15011. The present case suggests that HLA-DR15 plays an important role on antibody production against alpha 3(IV) NC1 autoantigen after severe nephritis or tissue damage.     

Mechanisms of Pancreatic B-Cell Degeneration during the Course of Insulin-dependent Diabetes Mellitus

ABSTRACT. This paper presents a review of different mechanisms possibly responsible for the degeneration of the pancreatic B-cell in insulin-dependent diabetes mellitus. The genetic dependence probably located in the HLA DR-locus of the sixth chromosome and its role in an autoimmune reaction against antigenieally altered pancreatic B-cells is discussed. The actions of alloxan and streptozotacin in the induction of experimental diabetes, as models for postulated human B-cytotoxins, are described.