急性脑损伤患者血清TNF-α、IL-6、IL-8、全血hs-CRP、CD3^＋／HLA-DR^＋水平的变化及临床意义

目的动态监测急性脑损伤患者血清肿瘤坏死因子-a（TNF-a）、白介素-6（IL-6）、白介素-8（IL-8）及全血超敏C-反应蛋白（hs-CRP）、CD3^＋／HLA-DR^＋水平的变化,为临床提供脑组织损伤严重程度的参考及评价预后方法将126例急性脑损伤患者分为4组（轻型组、中型组、重型组、特重型组）,监测不同时间段（〈12h、24h及第3、5、7天）TNF-a、IL-6、IL-8、hs-CRP、CD3^＋／HLA-DR^＋的水平并进行比较分析。结果4组患者伤后12h内TNF-a、IL-6、IL-8、hs-CRP、CD3^＋／HLA-DR^＋水平均升高,TNF-a、IL-6、IL-8水平在伤后第3天达到高峰,轻型组、中型组、重型组上述指标水平均持续下降,而特重型组伤后第7天仍保持较高的水平（P〈0.05）。TNF-a、IL-6、IL-8水平升高与颅脑损伤程度呈正相关（P〈0.05）。TNF-a、IL-6、IL-8、CD3^＋／HLA-DR^＋水平升高又与hs-CRP呈正相关（P〈0.01）。结论脑损伤患者体内存在不同程度的炎症和免疫反应。脑损伤急性期,炎性反应因子TNF-a、IL-6、IL-8、hs-CRP及血管损伤的细胞因子CD3^＋／HLA-DR^＋表达与血肿的扩大密切相关,各类参与炎性反应的因子相互促进和调节,动态监测有助于早期判断脑损伤的严重程度和预后评估。     

Serologically HLA-DR—Mismatched Unrelated Donors Might Provide a Valuable Alternative in Allogeneic Transplantation: Experience from a Single Japanese Institution

To clarify the clinical significance of a serologic HLA-DR mismatch after unrelated-donor transplantation, we evaluated for hematologic malignancies 123 cases of unrelated bone marrow transplantation carried out in a single institution between 1995 and 2004. Of the patients in these cases, 12 were serologically mismatched at the single HLA-DR locus. Eighty-two patients who received HLA-matched transplantations were used as controls. Conditioning consisted of a conventional total body irradiation-based regimen or a fludarabine-based reduced-intensity regimen. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus plus short-term methotrexate. Graft failure did not develop. With a median follow-up of 42 months (range, 11-99 months), rates of overall survival, nonrelapse mortality, and relapse at 4 years were 63%, 38%, and 0%, respectively, all of which were comparable with those after HLA-matched transplantation. The frequency of acute GVHD of grades II to IV was 75%, significantly higher than after HLA-matched transplantation (42%, P = .046), and there was a trend toward an increased incidence of acute GVHD of grades III to IV after serologically HLA-DR-mismatched unrelated transplantation (27% versus 10%, P = .093). Chronic GVHD developed in 4 of 11 evaluable patients, an incidence comparable with that after HLA-matched transplantation. In summary, serologically HLA-DR-mismatched unrelated transplantation is feasible and might be an acceptable alternative for the Japanese population, although the higher incidence of acute GVHD is notable.     

Association of HLA-DR and -DQ Genes with Familial Moyamoya Disease in Koreans

Objective

Moyamoya disease (MMD) is an uncommon cerebrovascular disorder, characterized by progressive occlusion at the terminal portion of the internal carotid artery. Incidence of the disease is high in East Asia and familial MMD accounts for about 15% of the disease. Although the pathogenesis is unknown, association of HLA class I or II alleles with MMD has been reported with conflicting results. We investigated whether there is a difference in HLA class II association between familial and non-familial forms of the disease.

Methods

A total of 70 Korean children with MMD, including 16 familial cases (10 probands), and 207 healthy controls were studied. Among familial cases, only 10 probands were used for the HLA frequency analysis. High resolution HLA-DRB1 and DQB1 genotyping was performed using polymerase chain reaction (PCR)-sequence specific oligonucleotide hybridization and PCR-single strand conformation polymorphism methods.

Results

The phenotype frequencies of HLA-DRB1^*1302 (70.0%) and DQB1^*0609 (40.0%) were significantly increased in familial MMD compared to both controls [vs. 15.5%, corrected p (p_c) = 0.008, odds ratio (OR) = 12.76; vs. 4.3%, p_c = 0.02, OR = 14.67] and non-familial MMD patients (vs. 14.8%, p_c = 0.02, OR = 13.42; vs. 1.9%, p_c = 0.02, OR = 35.33). The frequencies of DRB1 and DQB1 alleles in non-familial MMD patients were not significantly different from those in controls.

Conclusion

Our findings suggest that the genetic polymorphism of HLA class II genes or other closely linked disease relevant gene(s) could be a genetic predisposing factor for familial MMD.     

免疫相关基因Tap2、HLA-DR9与新疆哈萨 克族食管癌的交互作用

 目的探讨Tap2379、Tap2665基因多态性、HLA-DR9等位基因频率与新疆哈萨克族(简称哈族)食管癌 的相关性。 方法采用1∶2配比的病例对照研究,收集哈族食管癌194例,健康对照388例,运用序列特异 性引物聚合酶链反应 限制片段长度多态技术(PCR-RFLP)检测Tap2379、Tap2665基因多态性,序列特异 性引物聚合酶链反应（PCR）检测HLA-DR9等位基因频率,采用χ²检验、多因素条件Logistic回归进行统 计分析。结果病例组与对照组间比较,Tap2379基因型差异有统计学意义(χ²=18.247,P<0.05,OR=2.347 ,95%CI：1.587~3.471);Tap2665基因型差异无统计学意义(χ²=2.175,P>0.05,OR=1.317,95%CI： 0.919~1.899);HLA-DR9等位基因频率差异有统计学意义(χ²=13.443,P<0.05,OR=2.343,95%CI： 1.486~3.693)。多因素条件Logistic回归示：Tap2379位多态性分布、HLA-DR9等位基因阳性率、食管或 胃疾病史在哈萨克族食管癌和健康对照间存在差异。交互作用示：Tap2379位多态性与HLA-DR9等位基因 协同作用时可使食管癌的发生危险性增加到5.302倍(95%CI：2.363~11.900)。结论Tap2379位Val(G)→ lla(A)转变、HLA-DR9等位基因阳性为哈族食管癌的危险因素,两者对食管癌的发生存在效应修饰作用。     

HLA-DR等位基因与中国人群肺结核关联性的Meta分析

目的应用Meta分析方法探讨中国人群HLA—DR基因多态性与肺结核易感性的关系。方法通过全面检索查找已发表的有关中国人群肺结核与HLA—DR基因关联性的文献。以肺结核组和健康对照组的HLA—DR等位基因型频数分布的比值比为统计量,采用RevMan5．0．13进行Meta分析。结果符合纳入标准的文献共7篇。Meta分析及敏感性分析发现,病例组和对照组DR4、DR16、DRBI＊15和DRBI＊13．2的合并比值比及其95％可信区间分别为1．64（1．08,2．50）、2．08（1．32,3．28）、2．94（1．34,6．49）和0．32（0．14,0．72）。结论DR4和DR16可能是南方汉族人群的易感基因;DRBI＊15可能是北方汉族人群肺结核的易感基因,DRBI＊13．2可能是其保护基因。     

Effect of UVB radiation on the biosynthesis of HLA-DR antigens

Summary HLA-DR molecules on the surface of immunocompetent cells are thought to represent target structures for the immunomodulating effects of UV radiation during the induction of an immune response. We therefore investigated the effect of UVB radiation on the de novo synthesis of HLA-DR--chains in the cytoplasm and the expression of - and -chains on the surface of the human lymphoblastoid B-cell line Raji. Raji cells were UVB irradiated before biochemical experiments were performed. Cells were then metabolically labeled or radioiodinated and detergent lysates immunoprecipitated using antibodies directed against the - or the - and -chain of the HLA-DR molecule. Over a wide dose range, UVB-irradiated Raji cells were shown to still express HLA-DR determinants on their surface and, even more importantly, to be capable of synthesizing HLA-DR-, - and -chains in a normal fashion. Despite this, the functional capacity of Raji cells was impaired in a dose-dependent manner. UV radiation thus seems to exert its immunomodulating effects primarily at a different level than the incriminated immune-response-associated antigens, which are expressed as recognition structures on the surface of immunocompetent cells.     

Limitations of an ocular surface inflammatory biomarker in impression cytology specimens

Context: A number of ocular conditions, such as dry eye, are associated with inflammation on the surface of the eye leading to irritation and ocular pain. Many drugs such as chemotherapeutics, beta blockers, angiotensin-converting enzymes and so forth also cause dry eye but currently there are no validated ocular surface biomarkers available.

Objective: We evaluated sample stability, assay sensitivity, reproducibility and overall performance of impression cytology (IC) utilizing the cellular surface biomarker human leukocyte antigen DR-1 (HLA-DR) as an ocular surface inflammatory biomarker by flow cytometry in a fit-for-purpose validation study. Additionally, subjects classified as normal or having various degrees of dry eye were evaluated to determine if HLA-DR could demonstrate a clear separation between normal and dry eye samples.

Results: The assay demonstrated high dynamic range detecting a broad range of fluorescent intensities in healthy donors. Additionally, inter, intra and stability assay results demonstrated strong concordance and low variability. Overall CV% for both assays were less than 25% for all measured parameters. However, high variability was observed for donor samples assayed beyond day 10 post IC sample collection (4.2–110.8 CV%).

Discussion: HLA-DR expression demonstrated a progressive increase in patients with mild to severe levels of dry eye disease providing sufficient evidence it is sensitive enough to monitor inflammatory effects of dry eye when coupled with additional biomarkers and/or methodologies such as cytokine analysis or ICAM-1. This biomarker can be used to monitor ocular surface disorders in patients and to evaluate potential treatment options during drug development. Although our results demonstrate this methodology is reproducible for routine evaluation, limitations around sample integrity exist.

Conclusion: The ocular cell surface inflammatory biomarker, HLA-DR coupled with impression cytology is a simple non-invasive robust, specific and reproducible assay that can be utilized to measure inflammatory infiltrates on the surface of the eye in IC samples less than 10-days old.     

基因芯片技术在肾移植组织配型中的应用

目的比较基因芯片和特异性聚合酶链反应(PCRSSP)两种HLADR分型方法,探讨适用于肾移植供、受者分型的新方法。方法对60份肾移植供、受者的DNA样本同时采用基因芯片和PCRSSP进行HLADR分型,并进行分析比较。结果60例样本的两种分型方法结果完全一致56份,相同率达93%。结果不相同的样本共4份,经第三方验证,其中基因芯片分型漏1个位点2例、1个位点误判1例,PCRSSP分型漏1个位点1例。其中20份样本作了重复实验,其重复率达到96%。结论基因芯片用于HLA分型具有灵敏度高、效率高、标准化程度高的优点,是其它分型方法所无可比拟的,具有广阔的应用前景。     

Immunoreactivity for LN2 and LN3 distinguishes small cell carcinomas from non-small cell carcinomas in the lung

Immunoreactivity to LN2 and LN3, monoclonal antibodies that recognize components of the class II major histocompatibility complex, was assessed in 72 cases of non-small cell lung carcinoma (NSCLC) (32 biopsy specimens, 40 resection specimens) and 64 cases of small cell carcinoma (56 biopsy specimens, 8 resections) of the lung. All cases were reviewed independently by three pathologists for histological classification. Only 1 of the 64 small cell carcinomas showed immunoreactivity for LN2, and none of the 64 cases showed reactivity for LN3. Among the non-small cell carcinomas, 25 of 48 cases were positive for LN2 and 43 of 71 were positive for LN3; the sensitivity was greater for adenocarcinoma (78.5%) than for squamous cell carcinoma (37%). A combined sensitivity of 64.7% was observed when the results of LN2 and LN3 were combined, and this sensitivity was not significantly diminished in the biopsy subset of cases (59.4%). Differentiation within histological subtypes of NSCLC (ie, well, moderate, or poorly differentiated) did not alter test sensitivity. In conclusion, LN2 and LN3, used alone or in combination, appear highly specific for non-small cell carcinoma and moderately sensitive in both biopsy and resection specimens; therefore, these antibodies may be diagnostically useful in distinguishing small cell from non-small cell carcinoma of the lung.