Significance of low-level DSA detected by solid-phase assay in association with acute and chronic antibody-mediated rejection

We sought to clarify the controversial issue of whether detecting low‐level anti‐donor‐specific HLA antibody (HLA‐DSA) by single‐antigen flow‐bead assay (SAFB) may have a potential role in reducing acute and chronic antibody‐mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO‐compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA‐DSA was detected only by SAFB in 24 patients, although all of them showed negative T‐cell and B‐cell complement‐dependent cytotoxicity (CDC) crossmatches. The HLA‐DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA‐DSA was considered to be a desensitization candidate. The 52 patients found to have HLA‐DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double‐filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5‐year graft survival rate also improved after implementing SAFB (83.3–98.1%, P = 0.032). The RIT/DFPP‐induction protocol may improve graft survival even in patients with low‐level DSA.     

Sclerostin Antibody Treatment Increases Bone Formation,Bone Mass,and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

The development of bone‐rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long‐standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl‐AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six‐month‐old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency‐induced bone loss, at which point Scl‐AbII was administered for 5 wk. Scl‐AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency‐induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non‐ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody‐mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone‐related disorders, such as postmenopausal osteoporosis.     

抗人膀胱癌/抗VEGF双功能基因抗体对膀胱癌生物学行为的影响

目的:探讨抗人膀胱癌/抗VEGF双功能基因抗体对人膀胱癌生长及转移的影响。方法:通过构建人膀胱癌裸鼠皮下移植瘤模型并注射双功能抗体,观察肿瘤生长及盆腔淋巴结转移情况,同时采用免疫组化法检测肿瘤微血管密度值及凋亡的肿瘤细胞指数。结果:肿瘤大小:双抗组为(19.50±4.51)mm2,对照组为(57.62±8.31)mm2,两组比较P<0.01;肿瘤微血管密度双抗组为(2351±207)个,对照组(4356±548)个,两组相比P<0.05;凋亡指数双抗组为19.25,对照组为9.31,两者比较P<0.05;双抗组无一只发生盆腔转移,而对照组为75.0%,两组比较P<0.05。以上各项组间差异均有统计学意义。结论:抗人膀胱癌/抗VEGF双功能基因抗体对人膀胱癌具有良好的靶向性,能够通过抑制肿瘤微血管形成和加速肿瘤细胞凋亡,遏制实验性人膀胱癌的生长转移,为该抗体用于临床膀胱癌的治疗提供了一定的实验基础。     

视神经脊髓炎谱系疾病伴常见非器官特异性自身抗体的特点

目的 探讨伴有及不伴常见非器官特异性自身抗体的视神经脊髓炎谱系疾病(NMOSD)患者的临床特点。 方法 收集36例NMOSD患者,其中伴有常见非器官特异性自身抗体者26例(阳性组),不伴常见非器官特异性自身抗体者10例(阴性组),比较两组临床表现、实验室检查及影像学特点。 结果 36例NMOSD患者中伴有至少一种常见非器官特异性自身抗体者占72.22%,并以抗核抗体、抗SSA抗体、抗Ro-52抗体为主。阳性组患者发病年龄晚于阴性组,且更易合并非器官特异性自身免疫疾病及肿瘤;阴性组患者首发症状中,视神经炎/脊髓炎比例明显高于阳性组,而阳性组的脑脊液压力及蛋白含量均明显高于阴性组;两组间其他临床、实验室及病灶分布特点相似。 结论 伴有常见非器官特异性自身抗体的NMOSD患者中枢神经系统炎症反应更严重,更易合并非器官特异性自身免疫疾病及肿瘤。     

重症肌无力患者血清Titin抗体和RyR抗体的临床研究

目的探讨重症肌无力（MG）患者血清Titin抗体和Ryanodine受体（RyR）抗体的临床意义。方法采用ELISA法检测61例MG患者和35例健康体验者（正常对照组）的血清Titin抗体、RyR抗体、AChR抗体。结果MG组Titin抗体和RyR抗体阳性率均显著高于对照组（均P＜0.001）;合并胸腺瘤MG（MGT）组患者Titin抗体阳性率明显高于未合并胸腺瘤MG（NTMG）组（P＜0.01）;MGT组和NTMG组患者RyR抗体阳性率差异无统计学意义（P＞0.05）;晚发型MG患者中Titin抗体和RyR抗体阳性率均明显高于早发型MG患者（均P＜0.05）;全身型或重症型（ⅡA、ⅡB、Ⅲ、Ⅳ型）Titin抗体阳性率显著高于眼肌型（Ⅰ型）（P＜0.01）,而两组间RyR抗体阳性率未见统计学差异（P＞0.05）;MG患者Titin抗体和RyR抗体水平与肌无力严重程度相关分析呈正相关（r=0.520、0.487,均P＜0.01）。结论Titin抗体和RyR抗体检测有助于MG的诊断,且Titin抗体有助于鉴别MG患者是否伴随胸腺瘤及进行Osserman分型。Titin抗体与RyR抗体水平还与MG患者病情的严重程度相关,可应用于评估MG患者的病情与预后。     

LRP16基因的多克隆抗体制备及表达的探索

目的:制备人LRP16蛋白多克隆抗体并利用该抗体检测LRP16蛋白表达及亚细胞定位。方法:利用已构建的pRSET-C载体和LRP16基因组成的连接产物转化BL-21缺陷型大肠杆菌。诱导该基因原核表达,快速蛋白免疫法获取相应的多克隆抗体,利用免疫组化法观察LRP16基因产物在人多种组织中的表达差异。结果:成功获得高效的LRP16抗体,利用该抗体初步证实LRP16基因编码产物的在不同雌激素受体水平的组织分布特点。结论:制备的LRP16抗体及其全长基因可用于LRP16基因的生理功能及病理学研究,初步发现LRP16基因的表达与雌激素受体呈正相关。     

胰岛素样生长因子Ⅰ型受体在急性髓细胞性白血病中的表达及意义

目的 研究胰岛素样生长因子Ⅰ型受体(IGF-ⅠR)在急性髓细胞性白血病(AML)中的表达特点及抗IGF-Ⅰ R单克隆抗体对人急性早幼粒细胞白血病细胞株HL-60的作用.方法 通过流式细胞仪检测白血病细胞和HL-60细胞表面IGF-ⅠR的表达,并用鼠抗人IGF-ⅠR单克隆抗体(IGF-ⅠR MAb)作用于HL-60细胞,用CCK-8法检测细胞增殖,用流式细胞术检测细胞凋亡和细胞周期的变化.结果 IGF-Ⅰ R在急性髓细胞白血病和HL-60细胞普遍表达,原始细胞比例越高,IGF-Ⅰ R表达越强(P＜0.01).0.001～10.000 μg/ml的IGF-Ⅰ R MAb可抑制HL-60细胞生长,且随时间的延长和药物剂量的增大,这种抑制作用更加明显(P＜0.05).0.001～10.000 μg/ml浓度范围内,IGF-Ⅰ RMAb诱导HL-60细胞的凋亡率随药物浓度的增大而增高,但对HL-60细胞周期无显著影响.结论 IGF-Ⅰ R在急性髓细胞性白血病中普遍表达,IGF-Ⅰ R的高表达可能与细胞的恶性转化和白血病细胞的生长有密切关系.IGF系统对肿瘤细胞的促增殖及抗凋亡作用能被IGF-Ⅰ R单克隆抗体所阻断,IGF-Ⅰ R有可能成为抗白血病治疗的靶点.     

92例孕妇产前IgG抗体效价的微柱凝胶法检测

目的探讨微柱凝胶法检测对孕妇产前IgG抗体效价的意义。方法取92例夫妻血型不合的O型孕妇血清进行微柱凝胶法检测,并观察新生儿ABO新生儿溶血病(HDN)的发病情况。结果IgG抗A抗体效价≥64者17例,占39.53%;抗B抗体效价≥64者20例,占40.82%。IgG抗A抗体者的总发病率为12.20%,IgG抗B抗体者的总发病率为14.29%。2者的发病均出现在抗体效价≥64。结论产前检测IgG抗体水平具有重要的临床意义。     

91例免疫相关性皮肤病患者血清花粉IgG抗体检测结果分析

目的：检测免疫相关性皮肤病患者血清花粉IgG阳性情况。方法：采用Dot-ELISA法检测受检患者血清花粉IgG抗体。结果：56％受检患者血 清花粉IgG抗体阳性,其中荨麻疹、湿疹、接触性皮炎和过敏性紫癜等过敏性皮肤病患者血清花粉IgG抗体阳性率为83．0％,其它免疫相关性皮肤病为18．4％（P＜0．005）。血清花粉IgG抗体阳性的34例荨麻疹患者中,早春花粉抗体阳性高达91．2％,晚春花粉52．9％,夏秋花粉29．4％（P＜0．005）。结论：致敏性花粉与过敏性皮肤病有较大关系。春季花粉,特别是早春花粉,是本地区花粉相关性荨麻疹的主要致敏花粉。