Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.     

生物软件在序列分析过程中的运用

介绍了组合使用BLAST、FASTA/BLASTScan3.2,或用多序列比对软件,从数据库中快速提取大数量目标序列,最后用MEGA4快捷编辑整理大数量序列的方法。还介绍了一种生成核酸序列与其氨基酸序列相似性百分率整合表格的方法。简述了对引物设计的基本认识并介绍了多重引物兼容性筛选软件;对构建系统发育树的认识并引出分子进化树构建软件MEGA4的使用和PAUP 4.0常用建树命令模块。期望这些方法和软件的使用能解决生物序列分析过程的常见问题。     

肠内营养对乳腺癌术后化疗患者肠道菌群及生活质量的影响

目的研究肠内营养对乳腺癌术后化疗患者肠道菌群、生活质量、营养指标水平的影响。方法选取2012年7月至2018年1月于我院进行乳腺癌术后化疗的91例女性乳腺癌患者为研究对象,根据是否进行肠内营养将患者分为肠内营养组和对照组,观察化疗前后2组患者肠道菌群、生活质量、营养指标水平的变化及不良反应发生情况。结果治疗前2组患者肠道菌群、生活质量、营养指标水平差异无统计学意义(均P0.05)。治疗后,肠内营养组患者肠道双歧杆菌数量为(6.7±0.5)lg CFU/g、乳杆菌数量为(8.5±0.4)lg CFU/g,均显著高于治疗前,同时显著高于对照组(均P0.05)。治疗后肠内营养组患者出现反酸、腹胀、便秘等胃肠道不良反应的比例与对照组比较差异无统计学意义(均P0.05)。治疗后两组患者总体健康、认知功能、情绪功能、角色功能、社会功能、活力、躯体疼痛、躯体功能评分显著高于治疗前(均P0.05),且肠内营养组患者生活质量各指标的评分显著高于对照组(均P0.05)。治疗后肠内营养组患者血清总蛋白(TB)、血清清蛋白(ALB)、血清前清蛋白(PA)、转铁蛋白(TF)水平均显著高于对照组(均P0.05)。结论肠内营养可预防乳腺癌术后化疗患者肠道菌群的紊乱及营养不良的发生,安全有效,有助于提高乳腺癌患者的生活质量。     

Real-time imaging of the dynamics of secretory granules in growth cones

Secretory granules containing a hybrid protein consisting of the regulated secretory protein tissue plasminogen activator and an enhanced form of green fluorescent protein were tracked at high spatial resolution in growth cones of differentiated PC12 cells. Tracking shows that granules, unlike synaptic vesicles, generally are mobile in growth cones. Quantitative analysis of trajectories generated by granules revealed two dominant modes of motion: diffusive and directed. Diffusive motion was observed primarily in central and peripheral parts of growth cones, where most granules diffused two to four orders of magnitude more slowly than comparably sized spheres in dilute solution. Directed motion was observed primarily in proximal parts of growth cones, where a subset of granules underwent rapid, directed motion at average speeds comparable to those observed for granules in neurites. This high-resolution view of the dynamics of secretory granules in growth cones provides insight into granule organization and release at nerve terminals. In particular, the mobility of granules suggests that granules, unlike synaptic vesicles, are not tethered stably to cytoskeletal structures in nerve terminals. Moreover, the slow diffusive nature of this mobility suggests that secretory responses involving centrally distributed granules in growth cones will occur slowly, on a time scale of minutes or longer.     

研究报告：CRBGP通过抑制FAK-AKT通路和白介素-6的分泌抑制胶质瘤U251细胞的活性

目的电压门控钠通道(voltage-gated sodium channels,VGSCs)表达于胶质瘤U251细胞,并影响U251细胞的增殖、侵袭和凋亡。富含半胱氨酸的颊腺蛋白(cysteine-rich buccal gland protein,CRBGP)是一种从日本七鳃鳗颊腺中分离出来的VGSCs阻断剂。本文旨在探究CRBGP是否因具有VGSCs阻断功能从而能够抑制U251细胞的活性。方法首先采用MTT法检测了CRBGP对U251细胞增殖的作用,并分别利用莱特-吉姆萨、FITC-phalloidin和Hoechst 33258染色法观察CRBGP处理后U251细胞的形态、细胞骨架和细胞核。细胞外基质蛋白如IV型胶原蛋白、纤连蛋白和层黏连蛋白用于检测CRBGP对U251细胞黏附的影响。此外,本文采用transwell法检测CRBGP处理后U251细胞的迁移和侵袭能力,并通过Western blot方法探讨CRBGP诱导U251细胞凋亡并抑制其运动的内在机理。最后,通过酶联免疫吸附测定法检测CRBGP对U251细胞的抑炎效果。结果 CRBGP通过线粒体依赖途径诱导U251细胞凋亡,...     

Hypoderma actaeon: an emerging myiasis in roe deer (Capreolus capreolus)

Subcutaneous larvae of Hypoderma spp. (Diptera: Oestridae) were detected in the dorsal region in 10 roe deer, Capreolus capreolus (Artiodactyla: Cervidae), hunted in central Spain between January and March 2016. All larvae were found in the inner side of the hide during the skinning of the animals. The study of the morphological features of eight larvae of different stages collected from two animals allowed the identification of Hypoderma actaeon Brauer. The small size (4–5 mm) of some of the first instars suggests that the internal lifecycle of H. actaeon may be exclusively subcutaneous. This is the first confirmation of H. actaeon in roe deer; however, further studies to assess the spread of the parasite and to follow the evolution of this myiasis in roe deer are needed.     

2004—2018年青海省乙型病毒性肝炎流行病学特征分析

目的 了解青海省2004—2018年乙型病毒性肝炎(简称乙肝)流行病学特征,为乙肝防治工作提供科学依据。方法 对青海省15年间乙肝监测数据进行描述性流行病学分析。结果 15年来青海省共报告乙肝患者201931例,年平均报告发病率239.71/10万,总体呈下降趋势。2004—2018年西宁市乙肝报告病例98218例,占48.64%;果洛藏族自治州最低,乙肝报告病例6766例,仅占3.35%。玉树藏族自治州乙肝报告发病率最高332.89/10万,海东市最低133.43/10万,不同地区乙肝报告发病率有统计学意义(χ^2=21997.32,P<0.05)。报告病例主要分布在25~55岁人群中,50~<55岁组发病率最高为454.99/10万,0~<5岁组发病率最低为23.69/10万;男、女性别比为1.57∶1。报告病例职业分布以农、牧民为主,占47.19%。结论 青海省经过多年的计划免疫的实施,乙肝防控效果明显,2009年以后乙肝报告病例呈现平稳状况。     

MR 弥散加权成像对鉴别诊断良恶性椎体压缩性骨折的临床价值研究

目的：探讨MR弥散加权成像(DWI)鉴别诊断良恶性椎体压缩性骨折的临床价值。方法：对57 例经临床或病理证实的椎体 良恶性压缩性骨折患者行矢状位T1WI、T2WI、T2WI/FS 及DWI扫描,研究其在常规序列和DWI序列上的表现,将常规MR 序列 和DWI序列检出率进行比较,测量正常椎体及病变椎体的表观弥散系数(ADC)值,并进行统计学分析。结果：(1)MR 常规序列和 DWI序列(b=500s/mm2)表现：良性椎体压缩性骨折呈长T1 长或等T2 改变,T2WI/FS 呈高信号,DWI 可以呈高信号、等信号及低 信号;恶性椎体压缩性骨折呈长T1 长T2 信号,大部分病灶T2WI/FS 及DWI呈高信号,少数变现为低信号;(2)MR 常规序列和 DWI 序列(b=500s/mm2)病灶检出率的比较：T1WI、T2WI/FS 及DWI序列病灶检出率均高于T2WI 序列,其间的差别有显著性意 义(P<0.01),T1WI、T2WI/FS 及DWI序列病灶检出率之间无显著性差异(P>0.01);(3)ADC 值比较：在DWI(b=500 s/mm2)上,良性组 ADC 值为(2.03± 0.83)× 10-3mm2/s,恶性组ADC 值为(1.37 ± 0.75)× 10-3mm2/s,正常组ADC值为(0.36± 0.21)× 10-3mm2/s,成像条 件相同时,良性组高于恶性组,两组间有明显的统计学意义(P<0.05)。结论：DWI可较好的反映椎体的弥散特征,ADC值作为量化 指标可对良恶性椎体压缩性骨折进行可靠鉴别。     

蒙药材刺柏叶中槲皮苷的含量测定

本实验建立了蒙药材刺柏叶中槲皮苷的HPLC含量测定方法.色谱条件为:Diamonsil C18(4.6 mm ×250 mm,5μm)和Shim-Pack C18(4.6 mm× 250 mm,5μm),流动相:甲醇-0.01 mol/L磷酸二氢钾溶液-冰醋酸(40∶ 60∶ 1.5),检测波长:254 nm,流速:1.0 mL/min,柱温:30℃.槲皮苷进样量在40.2 ng ～603.0 ng范围内线性关系良好(r =0.9998),其平均加样回收率为100.45％,RSD为0.69％(n=6).本方法简便易行,结果准确,重复性好,可用于刺柏叶中槲皮苷的含量测定.     

北京市不同植物群落的降温增湿效应研究

在北京市植物园选取14个不同结构特征的植物群落作为研究对象,利用温湿度记录仪对其温湿度进行测定,分别研究郁闭度、平均冠幅、叶面积指数与降温增湿效应之间的相关性。结果表明,不同群落的降温增湿效果存在较大差异:碧桃(Prunus persica Batsch.var.duplex)、洋白蜡(Fraxinus pennsylvanica)、杂种鹅掌楸(Liriodendron chinense×tulipifera)、杜仲(Eucommia ulmoides)群落的降温增湿效果较好,而绦柳(Salix matsudana f.pendula)、楸树(Catalpa bungei)、毛泡桐(Paulownia tomentosa)群落的降温增湿效果相对较弱。对实验数据进行统计分析可知,郁闭度与群落降温效应呈极显著正相关,与增湿效应呈正相关但不显著;平均冠幅与群落的降温效应呈显著正相关,但与增湿效应的正相关并不显著;叶面积指数对群落的降温效应起到一定促进作用,但对增湿效应影响不大。除此之外,其他影响植物群落降温增湿效应的结构特征有待进一步探讨。