Comparison of the immunogenicity of Dukoral® oral cholera vaccine between renal transplant recipients on either a calcineurin inhibitor or mycophenolate – A controlled trial

BackgroundThe evidence for recommendations regarding vaccination in solid organ transplant recipients is sparse. There is little data comparing vaccine responses between groups on different immunosuppressive drugs. This study was conducted to evaluate the antibody response to Dukoral® oral cholera vaccine in renal transplant recipients (RTR).MethodsIn a single-center non-randomized controlled clinical trial, healthy volunteers (n = 21) and renal transplant recipients (n = 30) were vaccinated with the oral whole cell/recombinant B subunit cholera vaccine Dukoral® (Valneva Inc., Vienna, Austria). The RTR were stratified according to their maintenance immunosuppressive therapy: either prednisone and a calcineurin inhibitor (cyclosporine A or tacrolimus; P/CNI group; n = 15) or prednisone and mycophenolate (P/MMF group; n = 15). All volunteers ingested Dukoral® at baseline and at day 14. Serum samples were drawn at day 0 and day 21. The primary outcome was seroconversion, defined as either a 3-fold IgA serum titer increase in anti-cholera toxin B antibodies and/or a 4-fold rise in the serum vibriocidal titer.ResultsFollow-up was complete. Seroconversion after vaccination was 57% (standard error, SE 9%) in RTR and 81% (SE 9%) in healthy controls (Relative Risk, RR 0.70; 95% CI 0.48–1.02). When stratified according to maintenance immunosuppression, the seroconversion rate was 67% (SE 12%) in the P/CNI group (RR compared with controls 0.82; 95% CI 0.55–1.25) and 47% (SE 13%) in the P/MMF group (RR compared with controls 0.58; 95% CI 0.32–1.03).ConclusionAdverse events were mild to moderate and transient. The response to Dukoral was weaker and the seroconversion rate was lower in renal transplant recipients than in healthy controls. In particular, those using mycophenolate had a poor response. Nevertheless, more than half of the transplant recipients seroconverted. Therefore oral vaccines should not be discarded as a potential tool for protection of solid organ transplant recipients.This trial is registered in clinicaltrials.gov under NCT01109914.     

4种常用免疫抑制剂对器官移植术后口腔临床表现的影响

目的： 通过观察分析肝、肾或造血干细胞移植术后口腔临床表现,探讨移植术后4种常用免疫抑制剂对口腔临床表现的影响。方法： 收集118例接受4种常用免疫抑制剂他克莫司、西罗莫司、环孢素或吗替麦考酚酯的实体器官或造血干细胞移植术后患者,采用问卷调查、口腔临床检查,记录患者术后口腔临床表现和免疫抑制剂的使用情况,并采用SPSS 21.0软件包对数据进行统计学分析。结果： 术后使用他克莫司的患者,口腔苔藓样病变和唇炎的发生率均显著低于未使用他克莫司组（P<0.01）;术后使用环孢素的患者,口腔苔藓样病变的发生率显著高于未使用环孢素组（P<0.05）,且唇炎的发生率显著高于未使用环孢素组（P<0.01）;术后使用他克莫司的患者,苔藓样病变、唇炎的发生率均显著低于使用环孢素组（P<0.01);术后使用吗替麦考酚酯的患者,自觉口干的发生率显著低于未使用吗替麦考酚酯组（P<0.01）;术后使用西罗莫司的患者,口腔临床表现发生率无明显降低。结论： 移植术后使用他克莫司,可改善口腔苔藓样病变和唇炎的症状,效果优于环孢素。使用吗替麦考酚酯可改善患者自觉口干症状。     

Disseminated bartonellosis in a child with steroid-dependent nephrotic syndrome receiving mycophenolate mofetil monotherapy

Cat scratch disease, usually a benign infectious disease, may develop as multisystem disease with multiorgan involvement, particularly in immunocompromised patients. We report on a patient who developed disseminated bartonellosis while receiving mycophenolate mofetil monotherapy treating steroid-dependent nephrotic syndrome, highlighting that severe infection can be observed in those patients. Therefore, this category of patients should be cautious when having contact with kittens and receives proper prevention advice.     

霉酚酸酯对糖尿病大鼠肾脏基质金属蛋白酶9、转化生长因子β1表达的影响

目的 探讨霉酚酸酯（MMF）对糖尿病（DM）大鼠肾脏的保护作用及其机制。 方法 将实验动物分为正常对照组、DM组及MMF治疗组。MMF组给予MMF(15 mg/kg,口服,1次/d) 治疗。8 周后检测各组大鼠尿蛋白量（24 h）、内生肌酐清除率（Ccr）、血糖;HE染色观察肾脏病理改变;免疫组化及RT-PCR法检测肾组织中基质金属蛋白酶9（MMP-9）、转化生长因子β1（TGF-β1）的表达。 结果 DM组大鼠血糖[（22.18±3.36） mmol/L比（6.40±0.87）mmol/L]、尿蛋白量（24 h）[（26.80±0.82） mg比（6.64±1.42） mg]、Ccr[（0.220±0.380） ml/min比（0.098±0.015） ml/min]显著高于对照组（P ＜ 0.05）。MMF组的尿蛋白量（24 h）[（16.17±1.15） mg]、Ccr[（0.220±0.380） ml/min比（0.207±0.377） ml/min]均显著低于DM组（P ＜ 0.05）。与DM组比较,MMF组肾小球肿大、系膜细胞增生显著减轻。肾组织中MMP-9在对照组表达较多,主要在肾小球系膜细胞胞质内及肾小管上皮细胞,DM组表达较弱,MMF组介于两组之间,组间差异均有统计学意义（P < 0.05）。TGF-β1在正常对照组大鼠肾组织有少量表达,在DM组表达较强,在MMF组介于两组之间,组间差异亦均有统计学意义（P < 0.05）。 结论 MMF可降低DM大鼠尿蛋白排泄、Ccr,减轻早期肾小球肥大,此作用可能与MMF上调肾组织中MMP-9表达、下调TGF-β1的表达、减少系膜外基质的沉积有关。     

吗替麦考酚脂治疗增殖性狼疮性肾炎的Meta分析

目的 评价吗替麦考酚脂(MMF)治疗增殖性狼疮性肾炎（PLN）的疗效和安全性。方法 检索Cochrane图书馆、PubMed、EMBASE、中国生物医学文献光盘数据库、中国期刊全文数据库和中国维普数据库等中关于MMF治疗PLN疗效和安全性的RCT文献,检索时间均从建库至2009年6月30日,由3名系统评价员进行文献资料提取和质量评价。评价指标为终末期肾病(ESRD)发生率、病死率、完全缓解率、部分缓解率、总缓解率、复发率和不良反应（闭经、感染、带状疱疹、WBC减少和胃肠道反应等）发生率。采用RevMan 5．0软件进行Meta分析。结果 共检索到868篇文献,符合纳入标准的14篇RCT文献（n＝1 032）进入Meta分析。文献质量评价7篇为B级,7篇为C级。Meta分析结果显示：①MMF组完全缓解率（OR＝2．16,95％CI：1．31～3．55）、总缓解率（OR＝1．51,95％CI：1．10 ～2．07）显著高于环磷酰胺（CTX）组;MMF组闭经发生率（OR＝0．16,95％CI：0．05～0．50）、感染发生率（OR＝0．38,95％CI：0．23～0．61）和WBC减少发生率（OR＝0．43,95％CI：0．27～0．71）均显著低于CTX组;两组病死率、ESRD发生率、部分缓解率、胃肠道反应发生率和带状疱疹发生率差异均无统计学意义。②MMF组病死率、ESRD发生率 、完全缓解率、部分缓解率、总缓解率、复发率、SCr倍增发生率 、胃肠道反应发生率、带状疱疹发生率与CTX/硫唑嘌呤（AZA）组差异均无统计学意义;MMF组闭经发生率（OR＝0．20,95％CI：0．07～0．61)、感染发生率（OR＝0．46,95％CI：0．22～0．99)和WBC减少发生率（OR＝0．12,95％CI：0．03～0．52) 显著低于CTX/AZA组。结论 现有的证据显示,MMF疗效与CTX或CTX/AZA相近,安全性方面优于CTX或CTX/AZA。有关PLN患儿MMF的疗效需进一步的RCT研究予以明确。     

Mycophenolate Mofetil Is Effective and Well Tolerated in the Treatment of Refractory Acute and Chronic Graft-versus-Host Disease

We enrolled 11 patients with refractory graft-versus-host disease (GVHD) in a prospective trial evaluating the efficacy of mycophenolate mofetil (MMF). Four (67%) of the 6 patients with acute GVHD and all 5 patients with chronic GVHD responded to MMF.Ten (91%) of the 11 patients were able to decrease steroid use (median decrease, 86%; range, 25%-100%). After a median follow-up of 18 months (range, 1-65 months), 7 patients (64%) remained alive. The adverse events were infectious complications (36%), diarrhea (27%), and neutropenia (18%); the only patient discontinuing MMF did so because of grade 4 neutropenia.This preliminary study suggests that MMF is a well-tolerated agent and has a beneficial effect in the treatment of refractory acute and chronic GVHD.     

Long-standing refractory polymyositis responding to mycophenolate mofetil: a case report and review of the literature

The authors describe a young patient affected by long-standing polymyositis refractory to conventional treatment who showed a rapid and striking response to mycophenolate mofetil treatment.     

Comparison of high-performance liquid chromatography and enzyme-multiplied immunoassay technique to monitor mycophenolic acid in paediatric renal recipients

Therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) is recommended to guide immunosuppression. High-performance liquid chromatography with ultraviolet (HPLC-UV) or the enzyme-multiplied immunoassay technique (EMIT), used to measure mycophenolic acid (MPA) were compared in an exclusive paediatric renal transplant population. Twenty patients were included as part of the pharmacokinetics study of MMF, and 88 additional samples were drawn for TDM. Agreement between HPLC-UV and EMIT was assessed by the Bland-Altman method. With the two methods, pre-dose concentrations were not normally distributed. After logarithmic transformation, their mean was 0.79 +/- 1.16 mug ml(-1) and their mean difference was 0.34 +/- 0.16 mug ml(-1) [95% confidence interval (95%CI 0.30-0.38 mug ml(-1), with antilogarithmic values of these limits of 1.34-1.46 mug ml(-1)). Area under the curve (AUC)(HPLC) and AUC(EMIT) were normally distributed. Their mean was 52.42 +/- 25.91 mg x h/l and their mean difference was 15.22 +/- 8 mg x h/l (95%CI 11.99-18.45 mg x h/l), the Bland-Altman plot showing a bias proportional to the mean. Our data showed the absence of agreement between the HPLC and EMIT methods, with an average positive bias of 15% with the EMIT. Further studies are required to determine which method is best appropriate for TDM of MMF in children.     

吗替麦考酚酯联合地塞米松治疗RITP的临床观察

目的:评价吗替麦考酚酯联合地塞米松治疗难治性血小板减少性紫癜(RITP)的临床疗效及不良反应。方法:选择RITP患者32例,随机分为对照组和治疗组,各16例。对照组给予地塞米松40mg·d-1,口服,第1～4天,每月1次,疗程6个月;治疗组加用吗替麦考酚酯1.0g,bid,口服,第1～20天,每月1次,疗程6个月。治疗期间监测肝肾功能和血小板指标的变化,观察呕吐、腹泻、白细胞减少、感染等不良反应发生情况。结果:治疗组显效率为56.2%,总有效率为93.7%;对照组显效率为25.0%,总有效率为68.7%,2组显效率、总有效率比较有显著性差异(P<0.01)。2组治疗期间肝肾功能正常,均未见明显不良反应。结论:吗替麦考酚酯联合地塞米松治疗RITP优于单用地塞米松治疗,且未见明显不良反应。