Genetic susceptibility to gluten sensitive enteropathy in Irish setter dogs is not linked to the major histocompatibility complex

Abstract: Gluten sensitive enteropathy (GSE) in Irish setter dogs has been proposed as an animal model for human celiac disease (CD), in which the major histocompatibility complex (MHC) class II alleles HLA DQAl*0501 and DQBl*0201 play an important role. To investigate whether an orthologous MHC class II region is involved in canine GSE, we undertook a linkage study in two large families of gluten sensitive Irish setter dogs. A total of 44 dogs in these pedigrees were genotyped for DQA1, DQB1 and C.2202 alleles, along with 30 unrelated healthy Irish setters. No genetic linkage between the DQ or C.2002 loci and GSE was detected. In contrast to CD, susceptibility to canine GSE does not appear to be determined by variation within the MHC class II gene cluster. Therefore, canine GSE may not be an appropriate model for CD, but nevertheless remains an important disease for advancing knowledge of pathological processes in the intestine.     

Lp(a) lipoprotein is a major risk factor for cardiovascular disease: pathogenic mechanisms and clinical significance

The results of two previous and two recent studies of middle-aged males and females are presented to exemplify the clinical importance of lipoprotein (a) (Lp(a)) as a risk factor for atherosclerosis and coronary heart disease. In these studies various conventional and recently suggested risk factors were included and different methods for Lp(a) quantification were used. Lp(a) was a significant risk factor in all four studies. In the recent prospective case-control study, Lp(a) and cholesterol were found to act synergistically and predict primary acute myocardial infarction in Swedish males. A cholesterol level above 6.5 mmol/1 increased the risk of acute myocardial infarction if the Lp(a) level was above 200 mg/1. The plasma apo A-I level was a protective factor. In the other recent case-control study, an Lp(a) level above 500 mg/1 was a highly significant risk factor in Black and White US women with myocardial infarction or advanced coronary artery disease in addition to low density lipoprotein cholesterol levels above 130 mg/dl. A high apo A-I level was a protective factor. In these studies no other factors tested reached significance in multivariate logistic regression analysis. A hypothetical association between high Lp(a) levels and intracellular infection with Chlamydia pneumoniae is discussed. The results suggest that the Lp(a) level is useful in identifying high-risk individuals. Lowering low density lipoprotein cholesterol below 100 mg/dl (7lt;2.6 mmol/1) seems to be most important in both males and females with high-risk Lp(a) levels.     

High responsiveness of HLA-B57-restricted Gag-specific CD8+ T cells in vitro may contribute to the protective effect of HLA-B57 in HIV-infection

HLA-B57 has been shown to be associated with long-term asymptomatic HIV-1 infection. To investigate the biological mechanism by which the HLA-B57 allele could protect from HIV-1 disease, we studied both the number of CD8(+) T cells as well as CD8(+) T cell responsiveness directed to different HIV-1 Gag peptides presented by HLA-A2, -B8 or -B57. T cells specific for the HLA-B57 peptide KAFSPEVIPMF responded more readily and to a higher extend to antigenic stimulation in vitro than T cells specific for the HLA-A2 peptide SLYNTVATL or the HLA-B8 peptide EIYKRWII. This phenomenon was reproducible with T cells from individuals expressing HLA-B57 in combination with one or both of the other alleles and was persistent during long-term follow-up. Lower reactivity of A2- and B8-restricted T cells was not explained by mutations in the B8- or A2-restricted Gag-peptides. Moreover, no correlation between peptide mutation frequency and IFN-gamma production by the corresponding Gag-specific T cells was observed. In conclusion, functional differences were observed between T cells specific for HIV epitopes derived from the same protein presented by different HLA molecules. B57-restricted KAFSPEVIPMF-specific CD8(+) T cells have relatively high responsiveness, which could contribute to the protective effect of HLA-B57 in HIV infection.     

Does cyclosporine influence the results of cadaver retransplantation?

The results of cadaveric retransplantation in 55 recipients immunosuppressed with cyclosporine and prednisone were compared to 156 recipients of primary renal allografts. By 3 yr posttransplant, there is no significant difference in patient survival, but the yearly graft survival for primary (79%, 72%, 72%) as compared to retransplant (69%, 58%, 58%) recipients was significantly (p less than 0.05) better. There was no significant difference in rejection episodes or mean +/- SD serum creatinine (mg/dl) at 2 yr between primary (32%, 2.14 +/- 1.1) and retransplant (33%, 2.08 +/- 1.4) patients, respectively. Donor source, third kidneys, human leukocyte antigen AB and Dr matching, percent reactive antibody levels, and cause of first graft loss do not have significant impact on cyclosporine-treated retransplant outcome. However, retransplant patients who have lost a previous graft in less than 3 months continue to be at high risk for subsequent early graft loss. These results suggest that the combination of cyclosporine and prednisone is the preferred regimen for cadaveric retransplantation.     

c-myc反义寡核苷酸对肿瘤细胞表面抗原和对CD3AK杀伤敏感性的调节作用

目的：观察c-myc反义寡核苷酸上调人高转移性肺巨细胞腺癌PG细胞表面抗原分子的表达水平，提高免疫效应细胞杀伤敏感性的作用和机制。方法：PT－PCR方法检测c-myc mRNA表达水平的变化。MTT法检测细胞增殖活性和CD3AK杀伤活性的变化。流式细胞术检测细胞表面抗原表达的变化以及c-myc蛋白表达水平的变化。结果：c-myc反义寡核苷酸（1μmol/L）明显地抑制PG细胞c-myc mRNA和蛋白表达水平，显著提高细胞表面HLA－ABC、ICAM－1分子的表达，其表达率分别从68．44％、38．40％增高到83．16％和42．09％（P＜0．01）。CD3AK对反义寡核苷酸处理的PG细胞的不同效靶比杀伤活性，分别从40．0％、65．0％、74．0％增高到52．0％、74．0％、91．0％（P＜0．01）。结论：c-myc反义寡核苷酸通过抑制PG细胞c-myc mRNA和蛋白表达，上调PG细胞表面HLA－ABC、ICAM－1分子的表达水平，提高其对免疫效应细胞的杀伤敏感性。     

New TAP2 polymorphisms in Africans

Abstract: Polymorphisms in genes encoding transporters associated with antigen processing (TAP) have been associated with heterogeneity of disease progression in HTV-l-infected homosexual men. In our recent AIDS-related studies of cohorts from Rwanda and Zambia, four new polymorphic sites in the TAP2 coding region were detected by single-strand conformation polymorphism (SSCP) and confirmed by bi-directional nucleotide sequencing and restriction enzyme digestion. The first, a substitution of Thr (GCC) for Ala (ACC) at codon position 374 in exon 5, was found in about 13% of Rwandans and Zambians ( n =213). The remaining 3 new polymorphisms were seen in the 7th exon with changes of 458Thr-ACG to ACA, 466Gly-GGG to GGA, and 467Val-GTT to Ile-ATT, respectively. These 3 variants occurred exclusively on the same chromosome and appeared to have arisen together from the 374Thr-bearing allele. Analyses of the relationship between the 374Thr-457Ile segment and the nearby markers in DQB1 and DRB1 suggested the existence of a unique extended haplotype related to these newly identified variants.     

Differential Anatomical Expression of Transplantation Antigens Within the Normal Human Placental Chorionic Villus*

ABSTRACT: The expression of transplantation antigens by cells of the placenta was examined by immunohistological and immunoprecipitation procedures with defined conventional and monoclonal antisera to beta₂-microglobulin, DR and DC gene products, and H-Y antigen. Cells of the mesenchymal stroma within chorionic villi were positive by immunofluorescence for major histocompatibility complex antigens, and in male pregnancies for H-Y antigen, but the trophoblast was consistently negative for all antigen systems examined. Immunohistological examination of viable suspensions of cultured diploid trophoblast and of isolated membranes also gave negative results, and after radioiodination and solubilization of membranes, no detectable radioactive material was immunoprecipitated. These results provide further evidence that transplantation antigens are not expressed by human trophoblast. Since this is a fetal structure exposed directly to immunologically competent cells of the mother in the intervillous spaces, this observation may be relevant to the apparent lack of damaging maternal immune responses directed against the fetal homograft.     

MHC-Ⅰ类分子在肿瘤浸润性淋巴细胞识别人黑色素瘤细胞中的作用

应用人白细胞抗原－Ａ２阳性（ＨＬＡ－Ａ＋２）黑色素瘤病人的瘤块中分离得到的肿瘤浸润性淋巴细胞（ＴＩＬ），进行ＨＬＡ－Ａ２限制性ＴＩＬ抗人黑色素瘤细胞作用的研究。在实验中发现，ＴＩＬ对自身和同种异体的ＨＬＡ－Ａ＋２黑色素瘤细胞具有杀伤作用，而对ＨＬＡ－Ａ－２黑色素瘤细胞及ＨＬＡ－Ａ＋２非黑色素瘤细胞无作用。选择重组白细胞介素４（ｒＩＬ－４）＋肿瘤坏死因子α（ＴＮＦα）能促进黑色素瘤细胞ＨＬＡ－Ａ２表达量，并增强ＴＩＬ对瘤细胞的杀伤活性。抗ＣＤ３、抗ＨＬＡ－ＡＢＣ和抗ＨＬＡ－Ａ２单抗具有明显抑制ＴＩＬ的抗瘤细胞活性。结果表明ＴＩＬ杀伤黑色素瘤细胞依赖于Ｔ细胞受体（ＴＣＲ）对瘤细胞共同抗原的识别，并有主要组织相容性复合体－Ⅰ类分子参与。     

A novel human leucocyte antigen-DRB1 genotyping method based on multiplex primer extension reactions

We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01-16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.     

HLA-DRB1*07与慢性乙肝患者Th1/Th2因子表达水平的相关性

目的 :探讨广东地区汉族慢性乙型肝炎患者HLA DRB1 0 7与Th1 Th2因子表达水平的相关性。方法 :收集 12 0例广东地区汉族慢性乙肝患者新鲜抗凝血各 8ml,通过序列特异性引物套式PCR(PCR SSP)方法进行HLA DRB1 0 7检测 ,并同时用双抗体夹心法检测患者治疗前后外周血CD4 +T细胞分泌IFN γ、IL 2、IL 10和IL 4的水平。结果 :12 0例慢性乙肝患者HLA DRB1 0 7携带者 31例 ,携带率为 2 5 8% ,明显高于广东地区汉族人群的平均携带率 7 84 % ;HLA DRB1 0 7阳性患者IFN γ平均表达水平为 (1132 0 4± 75 36 )pg ml,IL 2平均表达水平为 (1184 0 6± 81 4 2 )pg ml,IL 4平均表达水平为 (876 79± 4 7 5 3)pg ml,IL 10平均表达水平为 (817 4 8± 2 4 4 0 )pg ml ;HLA DRB1 0 7阴性患者IFN γ平均表达水平为 (12 32 10± 198 13)pg ml,IL 2平均表达水平为 (12 0 8 17± 116 12 )pg ml,IL 4平均表达水平为 (6 81 99± 6 1 5 9)pg ml,IL 10平均表达水平为 (6 38 84± 76 17)pg ml。HLA DRB1 0 7阳性患者IL 4、IL 10表达水平高于阴性患者 (P <0 0 5 ) ,而IFN γ、IL 2表达水平与阴性患者差异无统计学意义 (P >0 0 5 )。结论 :HLA DRB1 0 7(+)慢性乙肝患者Th2因子表达水平高于HLA DRB1 0 7(- )慢性乙肝患者。