Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy

High resolution PCR-SSOP typing methods for HLA-B identification have been established and applied to a Northern Ireland population, using large enough numbers to give dependable allele frequencies. The six systems, which operate independently of each other, are intended for use as secondary typing systems following HLA-B identification with a medium resolution PCR-SSOP technique.     

HLA class I genotyping including HLA-B*51 allele typing in the Iranian patients with Behçet's disease

It is well known that Beh?et's disease (BD) is strongly associated with human leukocyte antigen (HLA) B51 in many ethnic groups. However, there has been no published report as yet with respect to this association among the Iranian people. Furthermore, since it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele typing as well as HLA class I genotyping of 48 Iranian patients with this disease. As a result, the frequency of the B*51 allele was significantly higher (62.1%) in the patient group as compared with the ethnically matched control group (31.8%) (Pc=0.067, R.R.=3.51). In the genotyping of B*51 alleles, 33 out of the 36 B*51-positive patients possessed B*5101 and the remaining 3 carried B*5108. This study revealed that Iranian patients with BD also had a strong association with HLA-B51. In addition, this significantly high incidence of HLA-B*51 was found to be caused by an increase in both the HLA-B*5101 and HLA-B*5108 alleles. However, there was no significant difference in the HLA-B*51 allelic distribution between the patient and control groups.     

Astrocytes and intracerebral immune responses

The astrocyte is the most abundant cell within the central nervous system (CNS). This cell subserves a multiplicity of important functions that contribute to the process of neural development as well as to the integrity of normal brain function. Adding to the already exhaustive list of capabilities, the astrocyte has now been demonstrated to function as an intracerebral antigen presenting cell. These findings are serving to revise our view of the brain as an immunoprivileged site and perhaps will shed some light on the pathogenetic mechanisms involved in a number of CNS disorders of immune dysregulation. In this review we provide some perspective on the regulatory mechanisms that influence astrocyte immune functions. Specifically, we address the role played by the major histocompatibility complex (MHC) antigens as well as adhesion molecules in the initiation of brain immune responses.     

An antigen processing polymorphism revealed by HLA-B8-restricted cytotoxic T lymphocytes which does not correlate with TAP gene polymorphism

In previous studies of antigen presentation through HLA-B27, we identified a healthy person whose lymphoblastoid cells do not present three B27-restricted viral epitopes to specific cytotoxic T lymphocytes (CTL), despite adequate cell surface expression of HLA-B2702 of normal sequence. Similar findings were observed in all members of his family sharing the HLA-A3-B2702 haplotype. The original donor, NW, carries HLA-B8 on his other class I haplotype, which his daughter, HW, has inherited. We now report a failure to present an HLA-B8-restricted epitope from influenza nucleoprotein following viral infection of NW cells, although exogenous added peptide is still presented normally. However, cells from HW, which do not carry the A3-B2702 haplotype, present the expected epitope after viral infection. Another B8-restricted epitope, from human immunodeficiency virus-gag, is presented equally well by both cell lines when infected with gag-vaccinia. This antigen processing phenotype does not correlate with any of the known human TAP-1 and TAP-2 polymorphisms.     

聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎的疗效和安全性

目的 探讨聚乙二醇α-2a干扰素（PEG INFα-2a）治疗HBeAg阳性慢性乙型肝炎的疗效和安全性。方法 按随机对照原则选择80例HBV DNA、HBeAg阳性的慢性乙型肝炎患者，按1：1随机分配进入PEG INFa-2a组和IFNα-2a组。结果 治疗6个月时，PEG INFα-2a组HBeAg血清转换率（45．7％）高于IFNα-2a组（35．1％），但P〉0．05。停药6个月后，持续的HBeAg血清转换率分别为48．6％和37．8％，P〉0．05。停药6个月后，持续的HBVDNA阴转率分别为62．9％和45．9％，P〉0．05。治疗后，两组的丙氨酸转氨酶（ALT）复常率差异无显著性，为62．9％和45．9％，停药后6个月，两组的联合应答率分别为57．1％和40．5％。PEG INFα-2a组有3例患者HBsAg阴转，而IFNα-2a组仅有1例患者HBsAg阴转。两组有相似的不良反应，不良反应间差异无统计学意义，两组治疗过程中均未发生重要的不良事件。结论PEG INFα-2a治疗HBeAg阳性的慢性乙型肝炎疗效优于普通干扰素IFN-2a，耐受性和安全性好。     

Immunogenetics of two new HLA alleles: A*0108 and B*4031

Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales.     

Identification of Antigen-Specific IgG in Sera from Patients with Chronic Prostatitis

Antigen-specific vaccines are one of several molecularly targeted approaches under investigation as possible treatments for prostate cancer. Important to the development of vaccines is the identification of appropriate target antigens. We hypothesized that antigens of the prostate might be identified in patients with the chronic prostatitis/pelvic pain syndrome, a syndrome for which an autoimmune pathology has been proposed. Such antigens might represent naturally recognized target antigens of the prostate that could be investigated in the future as prostate tumor antigens. In this report, we used SEREX to identify proteins expressed in a prostate cDNA expression library recognized by IgG from the sera of patients with chronic prostatitis. Candidate proteins were evaluated using a panel of sera from 62 subjects with symptomatic prostatitis and 71 control male blood donors. We identified one protein that was recognized primarily in sera from subjects with prostatitis compared with controls. MAD-PRO-34, a nucleolar autoantigen, was recognized in 6/62 subjects and 0/71 controls (p = 0.00897). This protein had previously been identified as an autoantigen in patients with prostate cancer. In addition, the NY-CO-7 protein was recognized in 9/62 subjects and 3/71 controls (p = 0.0654). Two subjects had IgG specific for both the MAD-PRO-34 and NY-CO-7 gene products. Our results demonstrate that some patients with the chronic prostatitis/pelvic pain syndrome have autoantibodies to specific proteins. Proteins identified, and MAD-PRO-34 in particular, could be further investigated as potential prostate tumor antigens.     

逆转录病毒载体介导的HBsAg抗原表达及其稳定性研究

目的 探讨逆转录病毒载体介导的HBsAg抗原的表达及其稳定性。方法 将HBsAg基因插入逆转录病毒载体PLXSN中，构建成重组逆转录病毒载体。用电穿孔法转染PA317细胞，包装成假病毒颗粒，在不同温度下冻存。于不同时间用假病毒颗粒感染HepG2、NIH3T3及293细胞，用RT—PCR及ELISA法检测HBsAg表达；以感染后G418抗性克隆形成数确定假病毒颗粒的活力。结果 在各个时间段HBsAg表达量均差异无显著性。在-20℃冻存时，6个月后克隆数即下降过半，12个月后仅形成少数克隆，24个月后无克隆形成；在-40℃冻存时12个月后HepG2、NIH3T3、293形成的克隆数分别为121、332和89，24个月后分别为42、137和43，与冻存前比较差异有显著性；-70℃冻存时，24个月后克隆数分别为159、463和112，与冻存前比较差异无显著性。结论 HBsAg重组逆转录病毒颗粒在-70℃保存2年后，病毒活力未受明显影响，HBsAg表达量亦无明显改变。     

A new HLA-B allele, B*1565, identified in three unrelated samples

Anew human leukocyte antigen-B allele, B*1565, has been identified during routine typing of cord blood samples. Subsequently, two individuals from the same family as the first cord blood sample plus two unrelated Australian Bone Marrow Donor Registry samples have been found to carry this novel allele.     

Biological properties associated with the enhanced lung-colonizing potential in a B16 murine melanoma line grown in a medium conditioned by syngeneic Corynebacterium parvum-elicited macrophages

A previous study by our laboratory showed that the peritoneal murine Corynebacterium parvum-elicited macrophages released into their growth medium an activity which enhanced the ability of B16-F10 melanoma cells to form experimental metastases in the lung of syngeneic mice. In the present study, we used a clone of B16-F10 line (F10-M3 cells) to investigate whether the increase in lung-colonizing potential due to the pro-clonogenic activity released by C. parvum-elicited macrophages was associated with biological properties characteristic of a metastatic phenotype. We have found that the pulmonary retention, growth rate in lung parenchyma, invasiveness through Matrigel, adhesiveness to IL-1-activated endothelium and MHC class I expression were increased in F10-M3 cells stimulated by the macrophage pro-clonogenic activity. By using an in vitro experimental protocol, the enhancement of lung-colonizing potential in the stimulated melanoma cells turned out to be a transient phenomenon as was the increase of invasiveness through Matrigel and the higher expression of MHC class I antigens. In conclusion, the melanoma cells stimulated by the pro-clonogenic activity released by C. parvum-elicited macrophages showed changes in biological parameters which are relevant to metastatic diffusion. These changes appeared as a temporary phenomenon which sustains the view that the metastatic phenotype represents a transient biological character influenced by host factors. This revised version was published online in July 2006 with corrections to the Cover Date.