利妥昔单抗治疗系统性红斑狼疮相关肺动脉高压的前景

肺动脉高压(PAH)是系统性红斑狼疮(SLE)的一种严重并发症,近期研究发现T、B淋巴细胞在PAH的发生过程中发挥重要作用。以B细胞为靶向,而同样对T细胞造成影响的利妥昔单抗(RTX)可能成为治疗SLE相关PAH(SLE-PAH)的有力武器。     

利妥昔单抗二线治疗免疫性血小板减少症4年观察

目的：观察分析利妥昔单抗治疗重型持续性免疫性血小板减少症的远期临床疗效。方法回顾性分析我科2009年~2013年在我科二线应用利妥昔单抗治疗的免疫性血小板减少症的患者24例,分析其完全缓解率、部分缓解率、无效率、有效时间,缓解持续时间、复发率、复发时间,副作用,并与既往报道的脾切除疗效、安全性对比。结果两组临床疗效及复发率比较差异无统计学意义。结论利妥昔单抗治疗重型持续性免疫性血小板减少症与脾切疗效相似,早期应用可能取得更好的效果,但均可能发生严重的并发症,部分可致命,应用时应谨慎。     

利妥昔单抗治疗视神经脊髓炎谱系疾病的疗效分析

目的：观察利妥昔单抗（RTX）治疗视神经脊髓炎谱系疾病（NMOSD）的疗效。方法：回顾性观察2008年1月至2018年11月中国人民解放军总医院129例NMOSD患者的治疗，其中55例血清水通道蛋白-4抗体（AQP4-Ab）阳性，74例AQP4-Ab阴性患者。通过90个月的长期随访，评估利妥昔单抗（RTX）、硫唑嘌呤（AZA）及吗替麦考酚酯（MMF）的治疗效果。AQP4-Ab阳性患者中，14例接受低剂量利妥昔单抗RTX治疗，13例接受AZA治疗，8例接受MMF治疗。结果：接受免疫治疗的AQP4-Ab阳性患者中，治疗后的年复发率（ARR）明显低于治疗前的ARR(RTX治疗组ARR从1.00降至0.70,AZA治疗组从0.80降至0.30,MMF治疗组从0.85降至0.35)。同时在AQP4-Ab阴性患者中，治疗后的ARR也低于治疗前（RTX治疗组从0.30降至0.20,AZA治疗组从0.90降至0.50,MMF治疗组从0.90降至0.40）。免疫治疗后的残疾进展（EDSS）有所下降，AQP4-Ab阳性患者的EDSS评分下降（RTX治疗组从4.00分降至2.75分，AZA组从3.50分降至...     

低剂量利妥昔单抗治疗温抗体型自身免疫性溶血性贫血的系统评价

目的标准剂量利妥昔单抗(RTX)(375 mg/m2/周×4)已成为难治复发温抗体型自身免疫性溶血性贫血(w AIHA)的首选二线治疗。尽管如此,低剂量RTX治疗w AIHA的疗效仍值得探讨。方法通过对PUBMED数据库和CNKI数据库的文献检索,本研究共纳入13项临床研究,对172例患者进行系统评价。结果低剂量RTX(100 mg/周×4)治疗w AIHA总反应率达到87.8%,其中完全缓解(CR)率62.8%,部分缓解(PR)率25%。由于病例数少,各组报道复发率差异较大,从0~62.5%不等,复发后再治疗仍有有效病例报道。无严重不良反应。结论低剂量RTX治疗w AIHA安全有效,不良反应少。     

利妥昔单抗在肾移植后抗体介导排斥反应中的作用

背景：国外研究表明,利妥昔单抗在肾移植后抗体介导的排斥反应中具有良好的安全性及有效性,但中国尚缺乏此类研究及报道。 目的：探讨利妥昔单抗在肾移植后抗体介导的排斥反应中的安全性和有效性。 方法：将肾移植后病理诊断为抗体介导的排斥反应的患者18例分为2组,均进行免疫抑制治疗,药物组8例采用单剂利妥昔单抗治疗;对照组10例不使用利妥昔单抗治疗。 结果与结论：用药后6,12个月,药物组肌酐水平均低于同期对照组(P < 0.05)。用药后随访6-12个月,药物组1例患者出现巨细胞病毒血症,1例患者出现泌尿系感染,随访期间无威胁生命的感染发生,人/肾存活率为100%。结果证实,利妥昔单抗在治疗肾移植移植后抗体介导的排斥反应中安全有效。     

利妥昔单抗联合扶正解毒方治疗儿童原发性免疫性血小板减少症的疗效及对患儿Th17/Treg细胞比例的影响

探究利妥昔单抗联合扶正解毒方对儿童原发性免疫性血小板减少症（ITP）治疗效果及对患儿Th17/Treg细胞比例的影响。研究发现利妥昔单抗+扶正解毒方治疗儿童原发性ITP,可纠正其Th17/Treg细胞比例,强化免疫调节作用,改善患儿免疫功能。     

滤泡型小裂细胞性淋巴瘤利妥昔单抗治疗后转变为CD20阴性的弥漫大B细胞淋巴瘤临床病理分析并文献复习

目的：探讨B细胞恶性肿瘤美罗华(rituximab)治疗后复发伴CD20抗原表达丢失患者的临床病理学特征、免疫学表型、治疗及预后。方法：回顾性分析1例滤泡型小裂细胞性淋巴瘤患者经美罗华治疗后转变为CD20阴性的弥漫大B细胞淋巴瘤的临床病理资料，并结合相关文献进行复习。结果：患者于1987年以左侧腮腺区淋巴结肿大为首发症状，1988年行左侧腮腺区淋巴结活检诊断为滤泡型小裂细胞性淋巴瘤，先后进行了50个疗程的“COP、OP”方案化疗及短期局部放疗。1998年出现白细胞升高及淋巴细胞百分数升高，骨髓穿刺诊断为慢性淋巴细胞白血病。2012年3月至2014年3月因白细胞急剧增高多次使用“美罗华”治疗，2014年3月患者出现咽喉部不适，行会厌部取检，诊断为右侧舌根部CD20阴性的弥漫大B细胞淋巴瘤，经过3个疗程的“mini-CHOP”治疗及2次“美罗华”治疗后右侧会厌部肿块消失，2015年5月再次出现右侧颈部淋巴结肿大，经活检诊断为CD20阳性的弥漫大B细胞淋巴瘤。结论：美罗华治疗恶性B细胞淋巴瘤后CD20抗原表达丢失在临床中并非罕见，建议临床中对于美罗华治疗复发或不敏感的病例重新取组织活检进行病理诊断、免疫标记，必要时进行分子遗传学检测，以免误诊，并可对复发病因的药物调整起到的积极指导作用。     

苯达莫司汀联合利妥昔单抗治疗滤泡性淋巴瘤一例

滤泡性淋巴瘤(follicular lymphoma, FL)是一种起源于滤泡生发中心B细胞(中心细胞和中心母细胞)的淋巴瘤, 一线治疗方案为化疗联合利妥昔单抗(rituximab, R)。盐酸苯达莫司汀是一种具有全新结构的抗癌药物, 其疗效显著, 副作用轻微, 药物稳定性优良, 能够显著降低疾病的复发率与死亡率。我科收治一例滤泡性淋巴瘤的患者, 以苯达莫司汀联合利妥昔单抗治疗, 效果良好, 现报告如下。     

阿卡替尼增强利妥昔单抗生物类似药HLX01对非GCB型DLBCL耐药细胞株的杀伤效果

目的:探索阿卡替尼(Aca)联合利妥昔单抗(RTX)生物类似药HLX01增强对耐RTX的非生发中心B细胞样(非GCB型)弥漫大B细胞淋巴瘤(DLBCL)细胞株杀伤效果的相关机制.方法:(1)采用RTX浓度梯度递增结合大剂量间断冲击的方法在体外构建耐RTX的人非GCB型DLBCL细胞株NU-DUL-1-R.流式细胞术检测...     

自体外周血干细胞移植联合利妥昔单抗治疗弥漫大B细胞淋巴瘤及相关因子的表达北大核心

背景:目前国内已有较多采用利妥昔单抗联合自体外周血干细胞移植治疗弥漫大B细胞淋巴瘤的临床报道,但其作用机制还不是很明确。目的:对比分析利妥昔单抗联合自体外周血干细胞移植与利妥昔单抗治疗弥漫大B细胞淋巴瘤的效果与相关因子水平的变化。方法:选择96例弥漫大B细胞淋巴瘤患者为研究对象,其中男62例,女34例,年龄20-75岁。48例采用利妥昔单抗联合化疗方案(对照组),另48例采用利妥昔单抗联合化疗、自体外周血造血干细胞移植方案(试验组),对比两组临床疗效、不良反应发生情况,随访记录患者生存期,治疗前、化疗6个疗程后及移植后6个月,检测两组血清血管内皮生长因子、碱性成纤维细胞生长因子及白细胞介素17水平。结果与结论:①试验组患者均采集到了足够的外周血造血干细胞,回输CD34+细胞数为(3.6±0.6)×106/kg,回输后中性粒细胞植入时间为(11.1±1.2)d,血小板植入时间为(12.3±2.4)d;②试验组治疗有效率明显高于对照组(81%,56%,P<0.05);③从确诊开始至随访结束,试验组生存率为79%、无进展生存率为50%,对照组生存率为56%、无进展生存率为31%,两组间生存率与无病生存率比较差异显著(P<0.05);④两组不良反应发生情况比较差异无显著性意义(P>0.05);⑤治疗前与化疗6个疗程后,两组间3种细胞因子水平比较差异无显著性意义;与治疗前比较,两组化疗6个疗程后的白细胞介素17水平升高(P<0.05),血管内皮生长因子、碱性成纤维细胞生长因子水平降低(P<0.05);与化疗6个疗程后比较,试验组移植后6个月的白细胞介素17水平升高(P<0.05)、血管内皮生长因子、碱性成纤维细胞生长因子水平降低(P<0.05),对照组3种细胞因子水平无显著变化(P<0.05);⑥结果表明,利妥昔单抗联合自体外周血干细胞移植可提高弥漫大B细胞淋巴瘤患者的生存期,其作用途径可能与调控白细胞介素17、血管内皮生长因子、碱性成纤维细胞生长因子水平有关。     

促肾上腺皮质激素应用于原发性肾病综合征频复发及激素依赖患儿疗效及安全性初探

目的探讨促肾上腺皮质激素（ACTH）治疗原发性肾病综合征（PNS）频复发或激素依赖患儿的疗效和安全性。方法以符合PNS频复发或激素依赖患儿为ACTH组,每月给予ACTH缓慢静滴3—5d,并逐渐激素减量至停药;以激素维持治疗PNS患儿为对照组。观察治疗前与治疗后3、6和12个月两组激素剂量、复发次数、肾上腺皮质功能及不良反应。结果2010年9～12月ACTH组纳入14例,对照组纳入6例。（1）ACTH组12／14例均能顺利将激素减量至停药,无复发;2例因感染尿蛋白波动,感染控制后尿蛋白仍阳性,激素加量至尿蛋白转阴后减量,继续ACTH冲击,其中1例因感染后再次复发,停用ACTH改用他克莫司。ACTH组13例进入分析。（2）ACTH组治疗后3、6和12个月激素剂量与治疗前差异有统计学意义（P〈0．05）;对照组治疗后3、6和12个月激素剂量与治疗前差异无统计学意义（P〉0．05）;ACTH组与对照组治疗后6、12个月激素剂量差异有统计学意义（P〈0．05）。③治疗前ACTH组和对照组均存在肾上腺皮质功能低下,ACTH组13例在治疗3、6和12个月分别有9、11和13例肾上腺皮质功能恢复正常;对照组6例12个月治疗期间均表现为肾上腺皮质功能低下。（4）ACTH组观察到腰部皮疹和心率加快各1例。（5）ACTH组治疗后6、12个月身高与治疗前差异有统计学意义,对照组治疗前后身高差异无统计学意义（P〉0．05）。ACTH组治疗前后体重差异无统计学意义,对照组治疗后6、12个月体重与治疗前差异有统计学意义（P〈0．05）。（6）ACTH组和对照组治疗前后骨密度差异均无统计学意义（P〉0．05）。结论ACTH治疗PNS频复发或激素依赖患儿有一定疗效,可避免长期激素治疗的不良反应,值得进一步探讨。     

Mesangial alterations in steroid-responsive minimal change nephrotic syndrome

Summary Renal biopsies from 25 children with steroid-sensitive minimal change nephrotic syndrome were evaluated retrospectively to determine whether there is any relation between the morphological changes and the frequency of relapses. Biopsy material was examined by light-, immunofluorescence-, and electron microscopy, and by morphometric methods. The patients were divided in a group of 15 children with frequent relapses (FR) and another group of 10 children with an absence of, or only infrequent, relapses (NR/IR). Semiquantitative evaluation of biopsy specimens disclosed no significant differences between groups, but morphometric measurements performed on toluidine stained semithin sections showed a significant increase of mesangial nuclei in FR compared with NR/IR (P<0.01). Furthermore, the mean area of mesangial nuclei was decreased and the relative frequency of smaller nuclear profiles was higher in patients with FR compared to NR/IR (p<0.01). These findings suggest mesangial cell activation in FR which may be related to a longer course of the disease prior to renal biopsy (mean 4.0 years in FR vs. 1.4 years in NR/IR). In our opinion, morphometric assessment of discrete mesangial alterations is a promising method for exploring clinicopathological correlations in minimal change nephrotic syndrome.Presented in part at the 5th International Symposium of Pediatric Nephrology, Philadelphia, USA, October 6–10, 1980     

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review

Objective

To describe safety and efficacy of rituximab in patients with systemic sclerosis.

Cyclosporin a treatment in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis

Summary In a pilot study 23 children with nephrotic syndrome were treated with cyclosporin A (Cs) for 6–45 months. 8 children suffered from steroid dependent minimal change nephrotic syndrome (MCNS) and had experienced at least one course with cytotoxic drugs, but had relapsed thereafter. 2 children had diabetes mellitus type I with nephrotic syndrome and 13 children had steroid resistant focal segmental glomerulosclerosis (FSGS). Cs was started with 100 mg/m2/day in two doses and increased stepwise to obtain a Cs whole blood trough level of 200–400 ng/ml. In steroid dependent MCNS treatment with Cs reduced relapse rate significantly, and prednisone therapy could be stopped completely. After discontinuation of Cs, relapses reoccurred as frequently as before. Renal function remained unimpaired despite repeated Cs treatment courses up to 38 months. In cases of nephrotic syndrome with diabetes type I Cs treatment led to complete remission without changing the insulin requirement. However, after discontinuation of Cs relapses reoccurred. In steroid resistant FSGS 6 children benefited from Cs treatment: 4 went into complete remission, 2 into partial remission. The 2 children with complete remission relapsed but remained Cs responsive. The remaining 7 children with FSGS did not respond to Cs but continued the course of their disease, with two patients rapidly progressing to terminal renal failure. Side-effects of Cs treatment were mild. It is concluded that Cs is an effective agent in steroid dependent MCNS and can be used as an alternative drug in specific cases like steroid toxicity or diabetes mellitus. In steroid resistant FSGS a trial with Cs seems to be warranted since some cases do respond favorably. To avoid nephrotoxicity treatment with Cs should always be monitored closely by determination of blood levels and renal function.Abbreviations MCNS minimal change nephrotic syndrome - FSGS focal segmental glomerulosclerosis - Cs Cyclosporin A     

Rituximab treatment for difficult-to-treat nephrotic syndrome in children:a multicenter,retrospective study

Background/aimThis study aimed to evaluate the efficacy of rituximab in children with difficult-to-treat nephrotic syndrome, considering the type of disease (steroid-sensitive or –resistant) and the dosing regimen.Materials and methodsThis multicenter retrospective study enrolled children with difficult-to-treat nephrotic syndrome on rituximab treatment from 13 centers. The patients were classified based on low (single dose of 375 mg/m²) or high (2-4 doses of 375 mg/m²) initial dose of rituximab and the steroid response. Clinical outcomes were compared.ResultsData from 42 children [20 steroid-sensitive (frequent relapsing / steroid-dependent) and 22 steroid-resistant nephrotic syndrome, aged 1.9–17.3 years] were analyzed. Eleven patients with steroid-sensitive nephrotic syndrome (55%) had a relapse following initial rituximab therapy, with the mean time to first relapse of 8.4 ± 5.2 months. Complete remission was achieved in 41% and 36% of steroid-resistant patients, with the median remission time of 3.65 months. At Year 2, eight patients in steroid-sensitive group (40%) and four in steroid-resistant group (18%) were drug-free. Total cumulative doses of rituximab were higher in steroid-resistant group (p = 001). Relapse rates and time to first relapse in steroid-sensitive group or remission rates in steroid-resistant group did not differ between the low and high initial dose groups. ConclusionThe current study reveals that rituximab therapy may provide a lower relapse rate and prolonged relapse-free survival in the steroid-sensitive group, increased remission rates in the steroid-resistant group, and a significant number of drug-free patients in both groups. The optimal regimen for initial treatment and maintenance needs to be determined.     

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%–15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n = 51; focal segmental glomerulosclerosis, n = 27; diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE 'D' allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the 'Ⅰ' allele was assessed as having very weak association in cases of minimal change disease. 'Ⅱ' genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of 'ID' genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.     

Electron microscopic findings suggestive of focal and segmental glomerulosclerosis in patients with steroid-resistant nephrotic syndrome

Distinction between minimal change disease and unsampled Focal Segmental Glomerulosclerosis is a challenging concept in kidney biopsy of patients with nephrotic syndrome with minimal histopathological findings. This study was performed to compare electron microscopic findings in patients with steroid-resistant nephrotic syndrome with minimal histopathological abnormalities and cases with Focal Segmental Glomerulosclerosis. This Cohort study was conducted in Cancer Institute, Imam Khomeini Hospital Complex, Tehran, Iran. Twenty patients with steroid-resistant nephrotic syndrome and minimal changes on the light microscopic study were selected as case group. Similarly, 20 patients with Focal Segmental Glomerulosclerosis were selected as the control group. Ultrastructural findings were re-evaluated and scored qualitatively (0–3+). In patients with minimal changes on light microscopic evaluation, clinical course of the disease was followed after 5 years. Mean ages of the patients (8 women and 12 men) in case and control groups were 12.9 and 15.9 years, respectively (p > 0.05). There was no significant difference in number of examined glomeruli and sampling from cortico–medullary junction area between the groups. The mean percentage of sclerotic glomeruli in control group was 15.4%. Tubular atrophy and interstitial fibrosis were more frequent in control patients. Podocyte proliferation, GBM duplication (involving more than 10% of capillary walls), and moderate to severe multifocal expansion of mesangial matrix were significantly more obvious in FSGS patient samples (p < 0.05). No statistically significant difference was found in severity of cytoplasmic vacuolization, GBM wrinkling and splitting between the groups. Most of (80%) the patients with minimal changes improved during the 5-year follow-up. Generally, we concluded that Podocyte proliferation, GBM remodeling, and moderate to severe mesangial matrix expansion are the most reliable findings on electron microscopic examination in favor of FSGS.     

Disseminated cryptococcosis in a patient with nephrotic syndrome

Disseminated cryptococcosis mainly occurs in patients with impaired cell mediated immunity. We present a case of disseminated cryptococcosis in a non-HIV patient with nephrotic syndrome who never received immunosuppression. Cultures of bone marrow aspirate, cerebrospinal fluid analysis and histology of skin lesions were all consistent with Cryptococcus neoformans infection. Treatment with amphotericin B followed by fluconazole was successful and in the course of two months when, the skin nodules disappeared.     

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis

Objective

To evaluate the efficacy and safety of rituximab for relapsing-remitting multiple sclerosis.