Familial hydronephrosis unlinked to the HLA complex

Clinical findings, management, and possible linkage of congenital hydronephrosis caused by ureteropelvic junction stenosis to the HLA complex were studied in four families. These families provide evidence of possible autosomal dominant inheritance. HLA class I antigen studies in all four and class II (HLA-DR) in three families were performed. These studies failed to show close linkage to the chromosome 6 markers in two families but there was consistent inheritance in the other two. Although formal linkage calculations are not presented, it is apparent that in some families HLA haplotyping is not useful in predicting prevence of renal obstruction. Am. J. Med. Genet. 70:118–120, 1997. © 1997 Wiley-Liss, Inc.     

Approaching the sensitized lung patient: risk assessment for donor acceptance

The presence of HLA antibodies is widely recognized as a barrier to solid organ transplantation, and for lung transplant candidates, it has a significant negative impact on both waiting time and waiting list mortality. Although HLA antibodies have been associated with a broad spectrum of allograft damage, precise characterization of these antibodies in allosensitized candidates may enhance their accessibility to transplant. The introduction of Luminex-based single antigen bead (SAB) assays has significantly improved antibody detection sensitivity and specificity, but SAB alone is not sufficient for risk-stratification. Functional characterization of donor-specific antibodies (DSA) is paramount to increase donor accessibility for allosensitized lung candidates. We describe here our approach to evaluate sensitized lung transplant candidates. By employing state-of-the-art technologies to assess histocompatibility and determine physiological properties of circulating HLA antibodies, we can provide our Clinical Team a better risk assessment for lung transplant candidates and facilitate a “road map” to transplant. The cases presented in this paper illustrate the “individualized steps” taken to determine calculated panel reactive antibodies (cPRA), titer and complement-fixing properties of each HLA antibody present in circulation. When a donor is considered, we can better predict the risk associated with potentially crossing HLA antibodies, thereby allowing the Clinical Team to approach allosensitized lung patients with an individualized medicine approach. To facilitate safe access of sensitized lung transplant candidates to potential donors, a synergy between the histocompatibility laboratory and the Clinical Team is essential. Ultimately, donor acceptance is a decision based on several parameters, leading to a risk-stratification unique for each patient.     

HLA基因与成人急性淋巴细胞白血病的相关性研究

目的:探讨HLA基因与成人急性淋巴细胞白血病(ALL)发病之间的关联。方法:采用序列特异性引物聚合酶链反应(PCR蛳SSP)DNA分型技术,对105 例成人急性淋巴细胞白血病患者和142名正常对照进行HLA基因分型,分析HLA基因分布频率在2组中的差异。结果:ALL组与正常对照组相比,A鄢0201(35.71 %)和B鄢4801(5.71 %)基因频率明显增高(RR=2.340 7、7.513 4,χ2=9.257 8、9.538 8 P<0.005),DRB1鄢0701基因频率(9.52 %)显著低于正常组(RR=0.439 2,χ2=6.990 2 P<0.01)。结论:HLA蛳B鄢4801和DRB1鄢0701基因可分别被认为是ALL白血病发病的危险标志和保护标志。     

HLA-A,B,C抗原在原发肺癌及其淋巴结转移灶中的表达

目的：研究肺癌及其淋巴结转移灶中人类白细胞抗原(HIA—A，B，C)的表达情况，并探讨其临床意义。方法：用抗HIA—A，B，C单克隆抗体W6/32，，以免疫组化S—P法检测67例肺癌和23例肺癌淋巴结转移灶中HIA—A，B，C抗原的表达。结果：6例小细胞肺癌，27例鳞癌和34例腺癌中HIA—A，B，C抗原表达下降率分别为100％，66．6％和38．2％，后两者相比差异有统计学意义(P＜0．05)；非小细胞肺癌中随着肿瘤分化程度下降，HIA—A，B，C抗原缺失率将增加(P＜0．05)，而与病人的TN分期无关；转移灶中HIA—A，B，C抗原的表达与其原发灶中相比普遍减低(P＜0．05)。结论：HIA—A，B，C抗原在肺癌中的表达明显低于正常肺组织；且与肺癌的组织类型和分化程度相关。     

PCR-RSSO基础上HLA-Ⅰ、Ⅱ基因分型的研究

目的通过对PCR-DNA技术的分析,探讨人类白细胞抗原(HLA)基因分型方法。方法采用PCR反向序列特异性寡核苷酸(polymerase chain reaction-reverse sequence specific oligonucleotide,PCR-RSSO)杂交技术,建立改良半量扩增体系全自动HLA-I、Ⅱ等位基因分型方法,进行了635份血液标本HLA-A、B、C、DR、DQ等位基因分型,其中166份DNA同时采用序列特异性引物技术(PCR-SSP)和手工全量扩增体系PCR-RSSO技术。对全自动半量PCR-RSSO、PCR-SSP、手工PCR-RSSO 3种方法做两两比较。结果全自动半量PCR-RSSO的分型成功率为98.4%(3 124/3 175),PCR-SSP为98.8%(656/664),手工PCR-RSSO为88.3%(733/830)。经χ2检验,全自动半量PCR-RSSO与PCR-SSP的分型成功率无统计学差异,与手工PCR-RSSO有显著差异(P<0.05)。结论PCR-RSSO可识别HLA-Ⅰ,Ⅱ共706个等位基因,覆盖WHO命名委员会2000年公布的936个等位基因的75.43%;对706个HLA等位基因的分型均为中~高分辨率,有分辨纯合子等位基因的能力;易长期保存书面的实验原始资料,即杂交条;具有成本低、劳动强度低、省时和DNA消耗量少等优点。PCR-RSSO适合于造血干细胞移植和建立造血干细胞及脐带血干细胞库的组织配型。     

采用基因配型行同种异体肾移植术

目的 探讨基因配型技术在同种异体肾移植中的应用。方法采用顺序特异引物聚合酶链反应法(PCR-SSP)分别进行供、受体的基因分型，为3例配型适当的终末性肾病患者行同种异体肾移植术，并观察其术后肾功能恢复情况。结果所有接受肾移植的患者于术后2d肾功能恢复至正常水平，无急性和超急性排异发生。随访11-15个月，各项检查指标均正常。结论 基因配型的准确率较之传统的血清学配型显著增加，显著提高同种异体肾移植的成功率。     

Human leucocyte antigens (HLA) and rheumatic diseases: HLA class ii antigen-associated diseases

The association between genes of the major histocompatibility complex, HLA in man, and disease susceptibility is one of the most intriguing discoveries of modern genetics. These studies are important for understanding the genetic basis, pathogenesis and aetiology of human diseases. With progress in these areas, new and better forms of treatment as well as disease prevention will become possible. In the previous paper, we reviewed the literature on associations between HLA Class I (A,B,C) genes and rheumatic disease. In this article, we will now concentrate on rheumatic disorders associated with genes in the HLA Class II region, including DR, DQ, DP and the transporter associated with antigen processing (TAP) genes. In addition, the role of the pathogenic mechanism(s), which results in an aberrant expression(s) of HLA molecules on the cell surface, in causing disease susceptibility will be examined.     

三种不同方法检测HLA-B27的比较

目的:比较强直性脊柱炎患者HLA-B27常用的三种检测方法的特点,探讨不同检测方法之间差异及各自优缺点,为临床检验提供参考。方法:采用ELISA法、RT-PCR法和流式细胞法,对120例强直性脊柱炎患者和100例正常对照人群进行HLA-B27检测,并对结果进行分析。结果:ELISA法、RT-PCR法和流式细胞法三种检测方法的敏感性、特异性和阳性、阴性预测值分别为83.3%、94.0%、94.3%、82.5%;95.8%、93.0%、94.3%、94.8%;93.3%、95.0%、95.7%、92.2%。结论:三种血清HLA-B27检测方法诊断AS的特异度均较高;PCR法和流式细胞法的敏感度均显著高于ELISA法,其中PCR法略高于流式细胞术。     

人食管癌Eca-109细胞Mr小于3000膜蛋白肿瘤抗原肽的筛选

目的:寻找被T细胞识别的食管癌细胞抗原肽,为食管癌免疫治疗奠定基础。方法:应用pH3.3的枸橼酸磷酸盐缓冲液间隔24h多次酸洗贴壁生长的Eca109细胞,获得人主要组织相容性复合体Ⅰ类分子(HLAⅠ)类分子结合的多肽,经超过滤,反相HPLC色谱层析得到不同组分多肽,DC递呈抗原肽刺激特异性细胞毒T淋巴细胞(CTL)反应,51Cr杀伤实验检测CTL对肿瘤细胞杀伤作用。结果:Mr小于3000的混合多肽经过反相HPLC可获得50多个组分,混合肽、P17、P29和P41组分体外诱导实验表明可以诱导出较强的CTL反应。结论:酸洗法能有效获得HLAⅠ类分子结合的多肽抗原,Mr小于3000的多肽成分中3个组分存在能引起特异性的抗肿瘤CTL免疫反应的肿瘤抗原,具有潜在的免疫治疗作用。     

伴重症肌无力的胸腺瘤HLA类分子表达强度分析

目的 通过比较伴重症肌无力(MG)的胸腺瘤、单纯胸腺瘤和正常胸腺中HLA类分子表达强度的差异，探讨伴MG胸腺瘤内异常微环境因素。方法 采用免疫组化方法检测HLA-Ⅰ(A、B、C)和HLA-DR表达，光镜下扫描图像入计算机，处理后得HLA类分子染色的积分光密度以分析其表达强度。结果 皮质型胸腺瘤HLA-DR表达强度减弱，伴MG皮质型胸腺瘤HLA-DR表达强度减弱程度更甚。结论 伴MG的皮质型胸腺瘤表达HLA-DR强度减弱可能是其内的胸腺细胞分化、发育异常的原因，可能与MG发病相关。