OKT3-induced nephrotoxicity is associated with release of group II secretory phospholipase A2

Abstract. Administration of the murine IgG2a CD3 monoclonal antibody OKT3 exerts a transient nephro-toxic effect. Increased levels of group II secretory phospholipase A₂ (sPLA₂-II) might account for this nephrotoxicity as sPLA₂-II induces the biosynthesis of prostaglandins, vasoactive lipid mediators that influence glomerular haemodynamics and renal function. Furthermore, extracellular phospholipases seem to be involved in proximal tubular cell injury. We studied plasma sPLA₂-II levels in relation to circulating creatinine, tumour necrosis factor α, interleukin 6 and C-reactive protein levels in 15 renal allograft recipients receiving rejection treatment with OKT3. As a control group, we studied 15 renal allograft recipients receiving rejection treatment with methyl-prednisolone. A maximal fourfold increase in sPLA₂-II levels was observed 48 h after the first OKT3 administration, preceded by increased tumour necrosis factor α and interleukin 6 levels and accompanied by increased C-reactive protein levels. Creatinine levels reached a maximal increase 72 h after initiation of treatment. During methylprednisolone treatment no increase in any of the studied parameters was observed. Thus, administration of OKT3 induces increased sPLA₂-II levels, presumably via generation of cytokines. We hypothesize that sPLA₂-II may contribute to the nephrotoxic effect of OKT3 by inducing vasoconstrictive prostaglandins and renal tubular cell injury.     

血清脂蛋白相关磷脂酶A2、同型半胱氨酸和血脂水平联合检测在脑梗死诊断中的应用价值

目的探讨血清脂蛋白相关磷脂酶A2(LP-PLA2)、同型半胱氨酸(Hcy)水平变化与脑梗死的相关性。并通过联合检测探讨血脂、血清Hcy和LP-PLA2对脑梗死诊断及鉴别诊断的临床价值。方法选取脑梗死患者65例(脑梗死组),以及同期健康体检合格的健康人64例(健康对照组)作为研究对象。检测各组参试者血清LP-PLA2、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、总胆固醇(CHO)和Hcy水平,并比较各组间差异。结果脑梗死组血清TG和LDL与健康对照组无明显差异(P0.05),但血清LP-PLA2和Hcy水平高于健康对照组(P0.01),血清HDL和CHO水平低于健康对照组(P0.01)。血清高Hcy和高LP-PLA2是脑梗死的独立危险因子,而高HDL是脑梗死的保护因子。在联合检测中,Hcy与LPPLA2联合检测优于单项检测和其他联合检测模式。结论脑梗死患者血清LP-PLA2和Hcy水平明显高于健康对照组,表明其可能参与脑梗死的发生,并可能成为早期预测脑梗死发生的生物学指标。Hcy与LP-PLA2联合检测对脑梗死的诊断具有较高的临床价值。     

脂蛋白相关磷脂酶A2在冠状动脉粥样硬化性心脏病患者中的临床应用价值

目的探讨血清脂蛋白相关磷脂酶A2(Lp-PLA2)在冠状动脉粥样硬化性心脏病(CAD)的临床应用价值。方法采用病例对照研究,选取2013年10月至2015年6月在该院进行冠状动脉CT血管造影(CTA)检查的患者790例,根据冠状动脉CTA结果分为CAD组(352例)和无CAD对照组(438例),CAD组依据冠状动脉病变支数不同分为单支冠状动脉病变(118例)、双支冠状动脉病变(107例)和多支冠状动脉病变(132例),检测Lp-PLA2、超敏C反应蛋白(hs-CRP)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、葡萄糖(GLU)、糖化血红蛋白A1c(HbA1c)等指标进行综合分析。各组均数比较采用t检验或方差分析;不同指标相关性采用Pearson直线相关分析。结果 CAD组和对照组比较,LpPLA2、hs-CRP、年龄、GLU、HbA1c、载脂蛋白B(ApoB)水平CAD组均明显高于对照组,差异均有统计学意义(均P0.05)。LpPLA2在CAD组不同冠状动脉病变支数间比较,差异有统计学意义(F=4.941,P0.05);多支冠状动脉病变组Lp-PLA2水平高于单支冠状动脉病变组,差异有统计学意义(P0.05);多支冠状动脉病变组和双支冠状动脉病变组Lp-PLA2水平差异无统计学意义(P0.05);双支冠状动脉病变组和单支冠状动脉病变组Lp-PLA2水平差异无统计学意义(P0.05)。Lp-PLA2和HsCRP之间用Pearson直线相关分析,结果显示无相关性(r=0.042,P0.05)。结论血清Lp-PLA2水平升高是CAD的危险因素,可用于冠状动脉粥样硬化及受累血管支数的风险评估。     

Neutrophil antigen 5b is carried by a protein, migrating from 70 to 95 kDa, and may be involved in neonatal alloimmune neutropenia

BACKGROUND: Neutrophil antigen 5b has been described as involved in transfusion reactions and not in neonatal alloimmune neutropenia. CASE REPORT: Anti-5b was found in the serum of a mother of a persistently neutropenic newborn, who had several bacterial infections. The neutropenia responded to treatment with recombinant human granulocyte-colony-stimulating factor. Immunoprecipitation experiments performed with this and three other 5b antisera identified a protein, migrating from 70 to 95 kDa, as carrier of 5b. The observed pattern of migration may point to heavy glycosylation of this protein. RESULTS: Six 5b-negative donors were identified among 54 screened white donors, for a 5b gene frequency of 0.66. CONCLUSION: Alloimmunization to 5b in pregnancy is rare. In the patients with neonatal neutropenia analyzed in the last decade, this was the first case discovered.     

血清学指标对2型糖尿病患者疗效的评估价值

目的探讨血清学指标对2型糖尿病(T2DM)患者疗效的评估价值。方法选择2018年1月至2019年3月该院内分泌科确诊并收治的T2DM患者60例作为观察组,选择同期于该院体检的健康人52例作为对照组。均于入院时抽取静脉血检测超敏C反应蛋白(hs-CRP)、脂蛋白相关磷脂酶A2(Lp-PLA2)、糖化血红蛋白(HbA1c)水平。对观察组进行血糖控制治疗1个月,根据患者治疗后疗效情况分为有效组、基本有效组、无效组,比较3组患者hs-CRP、Lp-PLA2、HbA1c水平,采用Spearman相关分析hs-CRP、Lp-PLA2与HbA1c相关性,采用受试者工作特征(ROC)曲线分析比较hs-CRP、Lp-PLA2、HbA1c对T2DM患者病情转归的评估价值。结果观察组hs-CRP、Lp-PLA2、HbA1c水平高于对照组,差异有统计学意义(P<0.05);有效组hs-CRP、Lp-PLA2、HbA1c水平低于基本有效组,基本有效组hs-CRP、Lp-PLA2、HbA1c水平低于无效组,差异有统计学意义(P<0.05);HbA1c与hs-CRP、Lp-PLA2均呈正相关(P<0.05);hs-CRP、Lp-PLA2、HbA1c联合检测对T2DM病情转归的预测价值优于单独检测(P<0.05)。结论hs-CRP、Lp-PLA2、HbA1c可作为评估TWDM疗效和预后的敏感指标,且三者联合检测可进一步提高对该病患者近期病情转归的评估能力。     

Establishment and application of an immunoassay for the simultaneous detection of IgG and its subtype IgG4 autoantibodies against M-type phospholipase A2 receptor

BackgroundThe renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed.MethodsWe established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls.ResultsThe sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %.ConclusionsThe dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis.     

有氧结合抗阻训练对原发性高血压患者血压变异性及血液相关指标的影响

目的 观察有氧结合抗阻训练对原发性高血压患者血压变异性（BPV）及血液相关指标的影响。 方法 将90例原发性高血压患者按照随机数字表法分为常规治疗组、有氧运动组、联合治疗组，每组30例。3组患者均给予常规降压药物治疗，有氧运动组在常规基础上增加有氧运动训练，联合治疗组在有氧运动组基础上增加抗阻训练。治疗前、治疗12周后（治疗后），观察3组患者24 h收缩压（SBP）、舒张压（DBP）的平均值及标准差，进行血液指标检查，计算血浆致动脉硬化指数。 结果 治疗前，3组患者24hSBP、24hDBP及24hSSD、24hDSD比较，差异均无统计学意义（P>0.05）。与组内治疗前比较，3组患者治疗后24hSBP、24hDBP均有所下降（P<0.05）。与常规治疗组比较，有氧运动组、联合治疗组治疗后24hSBP、24hDBP均显著下降（P<0.05）。与有氧运动组治疗后比较，联合治疗组治疗后24hSBP［（126.3±7.56）mmHg］、24hDBP［（84.2±5.1）mmHg］均显著下降（P<0.05）。与组内治疗前比较，有氧治疗组、联合治疗组治疗后24hSSD下降（P<0.05）。与常规治疗组治疗后比较，有氧治疗组、联合治疗组24hSSD下降（P<0.05）。3组患者治疗前AIP、Lp-PLA2比较，差异无统计学意义（P>0.05）。与组内治疗前比较，有氧运动组、联合治疗组AIP、Lp-PLA2均有所下降（P<0.05）。与常规治疗组比较，有氧运动组、联合治疗组AIP、Lp-PLA2均有所降低（P<0.05）。与有氧运动组治疗后比较，联合治疗组AIP（2.08±0.23）有所降低（P<0.05）。 结论 降压药物能够降低血压，但不能有效控制血压变异、降低血脂、改善动脉硬化指数。长期有规律的有氧运动能使中老年高血压患者BPV下降，血脂、动脉硬化指数降低、心血管疾病风险降低。有氧运动结合轻中度循环阻力运动在改善上述指标方面的效果较好。     

Mutation of the phospholipase catalytic domain of the Pseudomonas aeruginosa cytotoxin ExoU abolishes colonization promoting activity and reduces corneal disease severity

We have previously shown that ExoU, a type III secreted cytotoxin of Pseudomonas aeruginosa, causes acute cytotoxicity towards corneal epithelial cells in vitro, and contributes to corneal disease pathology and ocular colonization in vivo. Subsequently, we reported that ExoU represses phagocyte infiltration of infected corneas in vivo. ExoU has patatin-like phospholipase activity that is required for cytotoxic activity in vitro (mammalian cell injury and death) and for disease in a murine model of pneumonia. We hypothesized that the phospholipase activity was required for ExoU-mediated corneal disease and ocular colonization. Using the murine scarification model, corneal disease pathology was examined after inoculation with approximately 10(6)cfu of a P. aeruginosa effector mutant (PA103DeltaexoUexoT::Tc) complemented with either exoU (pUCPexoU), phospholipase-inactive exoU (pUCPexoUD344A) or a plasmid control (pUCP18). Eyes were photographed and disease severity scored at 24 and 48h post-infection. Viable bacteria colonizing infected eyes were quantified at 6 and 48h. Complementation with exoU caused significantly more pathology (increased disease severity scores) and enabled bacteria to better colonize (by approximately 1000-fold) at 48h as compared to phospholipase-inactive exoU which did not differ from plasmid control. Surprisingly, exoU did not contribute to early (6h) colonization. In-vitro assays confirmed that the phospholipase domain of exoU was required for cytotoxicity towards human corneal epithelial cells. Taken together these data show that the phospholipase activity of the P. aeruginosa cytotoxin, ExoU, plays a role in the pathogenesis of corneal infection via mechanism(s) occurring after initial colonization of a susceptible cornea.