抗CD20抗体治疗慢性特发性血小板减少性紫癜机制的研究

目的:通过抗CD20抗体(Rituximab,商品名:美罗华)与慢性特发性血小板减少性紫癜(cITP)骨髓体外培养,了解cITP患者B细胞的活化与凋亡的状况。方法:选择cITP患者30 例,对照组缺铁性贫血患者10例,进行骨髓体外培养,于培养前、培养3 d、培养6 d、培养9 d,检测B细胞相关分子(CD19、CD20、CD23)和透射电镜观测淋巴细胞凋亡状态。结果:cITP患者骨髓CD20、CD23分子表达显著高于对照组CD20、CD23分子表达(P<0.01)。加抗CD20抗体和加半量抗CD20抗体培养前后B细胞相关分子(CD19、CD20、CD23)检测结果差异有统计学意义(P<0.01)。加抗CD20抗体组透射电镜观测有淋巴细胞凋亡。结论:抗CD20 抗体能靶向性地与表达CD20抗原的B细胞结合,通过抗体抗原反应,诱导B细胞加速凋亡。     

儿童过敏性紫癜901例临床分析

目的 探讨近年来儿童过敏性紫癜(HSP)患病率和临床表现特点的变化.方法 回顾性分析我院儿科1995年1月至2005年12月住院的901例过敏性紫癜患儿的临床资料.结果 ①1995-2005年每年HSP住院构成比依次为23/2165(1.06%)、29/2098(1.38%)、24/1973(1.22%)、39/2008(1.94%)、54/2433(2.22%)、86/2611(3.29%)、94/2724(3.45%)、99/3014(3.28%)、138/2900(4.76%)、143/3177(4.50%)、172/3500(4.91%),呈逐年明显增高趋势;②48.6%的患儿有前驱感染史,4个家庭分别有2～3个亲属先后患本病.③部分患儿非典型起病,165例(18.31%)起病时皮肤无紫癜,其中90例以消化道症状起病,63例以关节症状起病,6例以肾受累症状起病,1例中枢神经症状起病,5例其他症状起病;14例以消化道症状起病的HSP患儿经胃镜检查呈胃、十二指肠黏膜小血管炎表现而于皮肤紫癜出现前拟诊.④95例(10.5%)有皮肤、关节、消化道、肾脏以外的系统受累,其中中枢神经系统受累30例,男性生殖器受累11例,胰腺受累3例,心脏受累47例,1例肺出血.结论 HSP患病率近年来有明显升高趋势.其家族集聚发病、不典型起病表现及多系统损害尤其是脑、肺、胰腺、心脏等重要脏器的受累值得重视.胃肠镜检查可助消化道症状起病的非典型HSP的早期诊断.     

丹参注射液联合孟鲁司特钠对过敏性紫癜患儿血清免疫学指标和炎症因子的影响

目的 探讨丹参注射液联合孟鲁司特钠对过敏性紫癜患儿免疫学指标和炎症因子的影响。方法 选取2016年11月—2018年11月安阳市中医院90例过敏性紫癜患儿为研究对象,根据就诊顺序均分为对照组（n=45）和观察组（n=45）。对照组在此基础上口服孟鲁司特钠咀嚼片,3～6岁：4 mg/次,1次/d,6～14岁：5 mg/次,1次/d。观察组患儿在对照组的基础上静脉滴注丹参注射液,0.5 mL/（kg·d）,加入到5%葡萄糖溶液250 mL中,每日不超过20 mL。两组患者均连续治疗2周。观察两组患者的临床疗效,同时比较两组治疗前后的血清免疫学指标和炎症因子水平。结果 治疗后,观察组患儿治疗总有效率为95.56%,对照组总有效率为77.78%,两组比较差异性显著（P<0.05）。治疗后,两组患者免疫球蛋白（Ig）A、IgE、补体C3水平均较治疗前明显降低（P<0.05）,且观察组IgA、IgE和补体C3水平显著低于对照组（P<0.05）。治疗后两组患者白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-26（IL-26）和肿瘤细胞坏死因子-α（TNF-α）水平较治疗前均显著降低（P<0.05）,且观察组细胞因子水平显著低于对照组（P<0.05）。结论 丹参注射液联合孟鲁司特钠可有效减轻血液系统炎性反应,调节免疫,临床疗效显著,在过敏性紫癜患儿治疗中具有较高的应用价值。     

儿童过敏性紫癜急性期免疫功能探讨

目的:总结儿童过敏性紫癜(Henoch-Schonlein purpura,HSP)的细胞及体液免疫特征,分析其与紫癜性肾炎(Henoch-Sch(o)nlein purpura nephritis,HSPN)的关系,探讨细胞免疫及体液免疫功能在HSP发病机制中的作用及临床检测价值.方法:HSP急性期患儿190例,按有无肾脏损害分为紫癜性肾炎组(HSPN)和非肾炎组(NHSPN),流式细胞仪免疫荧光法检测T淋巴细胞亚群、自然杀伤细胞(Natural killer cells,NK cells)、B淋巴细胞变化,ELISA法检测血清IL4、IL-10、TNF-α的含量,速率散射比浊法检测外周血免疫球蛋白IgG、IgM、IgA、IgE、C3、C4水平.结果:190例HSP患儿中,合并肾脏损害33例,不合并肾脏损害157例.与对照组相比,急性期HSP组CD19细胞绝对值、IL-4、IL-10、TNF-α、IgG、IgA、IgE、补体C3显著升高(P均＜0.05),CD3、CD4、CD8、NK细胞绝对值显著降低(P均＜0.05);HSP患儿中,HSPN组的IL-10、IgA水平高于NHSPN组(P＜0.05),两组之间其余指标的差异无统计学意义(P均＞0.05).IgA水平升高组HSPN发生率(21.64％)高于IgA水平正常组(7.14％,x2=5.785,P＜0.05).IL-10水平与IgA呈正相关(r=0.425 9,P＜0.05),IL-4水平与IgE呈正相关(r=0.541 7,P＜0.05).结论:HSP急性期存在细胞及体液免疫功能的紊乱,均参与了HSP的发病机制,表现为细胞免疫功能低下,引起炎性介质分泌增多,导致多克隆B细胞活化及免疫球蛋白的分泌增加,介导了系统性微小血管炎,其中IgA介导的体液免疫紊乱在HSP的发病机制中起了主要作用;HSPN的IgA水平升高更为显著,可能是预测HSP发生肾脏损害的一个危险因素.     

Effective and safe off-label use of caplacizumab treatment in a middle-aged obese male

This study shows clinical efficacy and safety profile of an off-label use of caplacizumab for the treatment of immune-mediated thrombotic thrombocytopenic purpura in a middle-aged obese male patient manifesting aphasia, weakness and unconsciousness. Routine blood tests revealed haemolytic anaemia, severe thrombocytopenia (platelet count = 20 × 10⁹/L) and moderate creatinine increase. Diagnosis was based on the clinical judgement and laboratory determinations (undetectable ADAMTS13 activity and presence of anti-ADAMTS13 antibodies). The patient underwent plasma-exchange and an adjunctive treatment with prednisone (1 mg/Kg/day), but the occurrence of a refractory and exacerbated form of disease suggested also using rituximab (375 mg/m² weekly for 4 weeks) and caplacizumab as salvage treatments. The caplacizumab was given at 10 mg/day subcutaneously without the first intravenous bolus. Because von Willebrand factor inhibition, platelet count recovery and remission of symptoms were achieved, use of caplacizumab with this scheme appeared to be as effective as the approved one. Although this is an off-label use, this case highlights the potential of this new treatment, in terms of drug's efficacy and safety.     

1例重症新型布尼亚病毒患者继发血栓性血小板减少性紫癜的护理

新型布尼亚病毒又称发热伴血小板减少综合征布尼亚病毒(severe fever with thrombocytopenia syndrome bunyavirus,SFTSV),是以发热伴血小板减少为主要特征的新型传染性疾病,临床表现主要为发热、血小板减少、白细胞减少及多器官功能损害[1]。每年4月至10月是新型布尼亚病毒的高发期。血栓性血小板减少性紫癜(thrombotic thrombocytopenic purpura,TTP)是一种严重的血栓性微血管病,临床表现为血小板减少、微血管病性溶血性贫血,以及神经系统损害、发热和肾损伤等。TTP的发生机制与严重的血管性血友病因子裂解酶(ADAMTS13)的活性降低密切相关,多数TTP患者起病急骤,病情凶险,如不及时救治,预后差,死亡率高达90%,血浆置换(plasma exchange,PE)是治疗TTP的首选疗法[2]。TTP患者通过PE去除血循环中抗ADAMTS13自身抗体,补充新鲜的ADAMTS13缺乏物质,可使患者病死率下降至8%~30%[3]。     

Evidence for a light chain restriction of glycoprotein Ib/IX and Ilb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP)

To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPHb/ Ilia-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IHa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes.     

Stenosing ureteritis in Henoch–Schönlein purpura: Report of two cases

Stenosing ureteritis (SU), a rare complication of Henoch–Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early‐stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non‐specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review.