冠心病病人红细胞分布宽度及超敏C反应蛋白的水平变化及意义

目的探讨冠心病病人红细胞分布宽度(RDW)及超敏C反应蛋白(hs-CRP)的水平变化及意义。方法选取2015年10月—2016年12月廊坊市第四人民医院心内科住院的冠心病病人236例,其中不稳定型心绞痛130例作为心绞痛组,急性心肌梗死106例作为心肌梗死组。比较两组冠状动脉病变支数、Gensini评分、RDW、hs-CRP水平及不同冠状动脉病变支数病人RDW、hs-CRP的水平,分析RDW、hs-CRP水平与Gensini评分、冠状动脉病变支数的关系。结果心肌梗死组冠状动脉病变支数、Gensini评分及RDW、hs-CRP水平均明显高于心绞痛组(P <0.05)。3支病变组RDW、hs-CRP水平明显高于1支病变组及2支病变组(P <0.05); 2支病变组RDW、hs-CRP水平明显高于1支病变组(P <0.05)。相关性分析显示:冠心病病人RDW、hs-CRP水平与Gensini评分及冠状动脉病变支数明显相关,RDW与hs-CRP呈正相关。结论急性心肌梗死病人RDW和hs-CRP水平较不稳定型心绞痛病人明显增高,且与冠状动脉病变程度呈正相关。     

巨噬细胞炎症蛋白1α与冠状动脉粥样硬化斑块病变相关性

目的 研究血浆巨噬细胞炎症蛋白1α水平在冠状动脉粥样硬化性心脏病患者的变化及与冠状动脉粥样硬化斑块病变严重程度及宽块稳定性的关系.方法 选择正常对照组25例及冠心病组84例(稳定型心绞痛26例,不稳定型心绞痛30例,急性心肌梗死28例),均采血测血浆巨噬细胞炎症蛋白1α;冠心病组患者均行冠状动脉造影记录冠状动脉病变支数及Gensini冠状动脉病变积分,并与血浆巨噬细胞炎症蛋白1α水平进行相关分析.结果 冠心病组血浆巨噬细胞炎症蛋白1α水平明显高于正常对照组(P<0.05).血浆巨噬细胞炎症蛋白1α水平在稳定型心绞痛组、不稳定型心绞痛组和急性心肌梗死组间以及轻、中、重度冠状动脉病变组(按Gemini积分分组)间均逐级升高,差异有显著性(P<0.05),但冠心病不同冠状动脉病变支数组间血浆巨噬细胞炎症蛋白1α水平差异无显著性(P>0.05).血浆巨噬细胞炎症蛋白1α水平与Gemini冠状动脉病变积分存在正相关(r=0.28,P<0.05).结论 冠心病患者血浆巨噬细胞炎症蛋白1α升高,可能是评价冠状动脉粥样硬化斑块病变严重程度及斑块稳定性的有效指标.     

血清基质金属蛋白酶3水平与冠心病及冠状动脉病变程度的关系研究

目的探讨血清基质金属蛋白酶3(MMP-3)水平与冠心病及冠状动脉病变程度的关系。方法选择2010年6月—2012年6月江苏大学附属武进人民医院心内科收治的冠心病患者127例,其中急性心肌梗死(AMI)患者50例(AMI组)、不稳定型心绞痛(UAP)患者37例(UAP组)、稳定型心绞痛(SAP)患者40例(SAP组)。另外选择同期在我院体检健康者50例作为对照组。采用ELISA法测定各组受检者血清MMP-3水平,比较各组受检者及不同冠状动脉病变支数患者血清MMP-3水平。结果对照组受检者血清MMP-3水平为(1.85±0.86)μg/L,SAP组为(1.77±0.96)μg/L,UAP组为(4.22±2.81)μg/L,AMI组为(6.37±1.68)μg/L。AMI组患者血清MMP-3水平UAP组SAP组和对照组(P0.05)。冠状动脉单支病变患者血清MMP-3为(3.72±1.88)μg/L,双支病变患者为(4.22±1.92)μg/L,三支病变患者为(4.86±2.24)μg/L,不同冠状动脉病变支数患者血清MMP-3水平比较,差异无统计学意义(F=0.438,P0.05)。结论血清MMP-3水平与冠心病患者冠状动脉病变程度无明显关系,但与动脉粥样硬化斑块的不稳定性有关,是急性冠脉综合征(ACS)的重要血清标志物。     

冠心病患者血清非对称二甲基精氨酸水平与冠状动脉狭窄程度的相关性

目的探讨血清非对称二甲基精氨酸与冠状动脉狭窄程度及冠心病病情的关系及其临床意义。方法选取75例行冠状动脉造影患者,并根据冠状动脉造影结果和临床表现分为稳定型心绞痛组(n=15)、不稳定型心绞痛组(n=23)、急性心肌梗死组(n=20)和对照组(n=17)。所有患者分别进行病史采集,并检测血脂、非对称二甲基精氨酸水平,应用Gensini积分系统评价患者的冠状动脉粥样硬化病变程度。分析血清非对称二甲基精氨酸水平与年龄、性别构成比、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及冠状动脉病变程度的相关性。结果与对照组血清非对称二甲基精氨酸水平(3.81±0.48μmol/L)相比,稳定型心绞痛组(4.82±0.50μmol/L)、不稳定型心绞痛组(5.52±0.55μmol/L)和急性心肌梗死组(6.03±1.13μmol/L)均明显升高,且差异有统计学意义(P<0.01);不稳定型心绞痛组和急性心肌梗死组血清非对称二甲基精氨酸明显高于稳定型心绞痛组,差异具有统计学意义(P<0.01)。急性心肌梗死组血清非对称二甲基精氨酸与不稳定型心绞痛组相比,虽有升高的趋势,但差异不具有统计学意义(P=0.279)。冠心病各亚组Gensini评分均明显高于对照组(Gensini评分为0),差异有统计学意义(P<0.01);稳定型心绞痛组Gensini评分(17.79±1.86)分别与不稳定型心绞痛组(38.05±4.46)和急性心肌梗死组(40.62±3.80)比较,差异有统计学意义(P<0.01)。血清非对称二甲基精氨酸水平与总胆固醇和低密度脂蛋白胆固醇呈正相关(P<0.01),而与年龄、性别构成比、甘油三酯、高密度脂蛋白胆固醇无显著相关性(P>0.05)。血清非对称二甲基精氨酸水平与冠状动脉狭窄程度Gnesini评分有明显相关性(r=0.704,P=0.000)。结论冠心病患者的血清非对称二甲基精氨酸水平与冠状动脉狭窄程度和冠心病病情的严重程度相关,监测血清非对称二甲基精氨酸水平对于判断冠心病病情、指导诊断治疗具有一定的价值。     

急性冠状动脉综合征患者血清类金属蛋白酶-9及C-反应蛋白检测的临床分析

目的观察急性冠状动脉综合征(ACS)患者血清类金属蛋白酶-9(MMp-9)及C反应蛋白(CRP)水平的变化并与稳定型心绞痛患者比较,分析MMp-9及CRP与ACS的关系.方法67例经冠状动脉造影证实为冠心病患者分为稳定型心绞痛及ACS二组,分别测定MMp-9及CRP的血清水平并进行分析.结果ACS患者MMp-9及CRP水平较稳定型心绞痛组明显增高,分别为(329.90±200.10)ng/L、(644.50±251.69)ng/L及(12.83±8.06)mg/L、(37.49±34.60)mg/L,P＜0.001,差异有统计学意义.结论MMp-9及CRP参与了ACS的发生发展过程.     

急性冠状动脉综合征患者血清热休克蛋白70的变化及其相关因素分析

目的 观察冠心病患者血清热休克蛋白70水平的变化及其相关因素进行分析.方法 共入选冠心病患者66例和无冠心病的健康对照者21例,再将冠心病患者分为急性冠状动脉综合征组46例(包括不稳定型心绞痛23例和急性心肌梗死23例)和稳定型心绞痛组20例.用ELISA测定血清热休克蛋白70水平,同时测定血清高敏C反应蛋白、空腹血糖、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及甘油三酯水平以及外周血白细胞计数等指标.结果 急性冠状动脉综合症组血清热休克蛋白70水平(4.72±2.01 μg/L)显著高于稳定型心绞痛组(2.33±1.44 μg/L)和对照组(2.41±0.96 μg/L;P<0.01),但在稳定型心绞痛组与对照组之间差异没有统计学意义(P>0.05).冠心病亚组分析显示,血清热休克蛋白70水平在急性心肌梗死组(5.94±1.98 μg/L)显著高于不稳定型心绞痛组(3.49±1.10 μg/L;P<0.01),在不稳定型心绞痛组显著高于稳定型心绞痛组(2.33±1.44 μg/L;P<0.01).线性相关分析发现,热休克蛋白70水平与白细胞计数(r=0.337,P<0.01)、肌酸激酶同工酶(r=0.653, P<0.01)及高敏C反应蛋白(r=0.658,P<0.01)呈正相关,与高密度脂蛋白胆固醇(r=-0.211,P<0.05)呈负相关.结论 血清热休克蛋白70水平可能是预测动脉粥样硬化斑块不稳定性和评估急性冠状动脉综合症病情严重程度的敏感指标.     

冠心病患者脑钠肽与冠状动脉病变程度的相关性研究

目的探讨脑钠肽与冠心病患者冠状动脉(冠脉)病变严重程度的相关性。方法入选行冠脉造影检查的冠心病患者173例,所有患者入院后均行冠脉造影检查及血浆脑钠肽(BNP)检查,分析不同冠脉病变支数、冠心病分型、冠脉病变程度(Gensini积分)与患者血清BNP水平之间的关系。结果随着冠脉病变支数增加,患者BNP水平呈显著增加趋势(P0.05)。稳定型心绞痛、不稳定型心绞痛、心肌梗死三组患者BNP水平呈显著增加趋势,三组BNP水平之间差异有统计学意义(P0.05)。BNP100pg/ml的患者Gensini积分显著高于BNP100 pg/ml的患者Gensini积分,分别为(53.7±15.9)分vs.(29.3±20.7)分,差异具有统计学意义(P0.05)。Gensini积分与BNP水平存在显著正相关(r=0.476,P0.05)。结论 BNP水平与冠心病患者冠脉病变严重程度正相关,BNP水平有可能作为冠心病患者冠脉病变严重程度的判断指标。     

血清脂蛋白相关磷脂酶A_2水平与冠心病关系

目的探讨冠心病患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)的水平与冠状动脉粥样斑块稳定性和冠状动脉病变程度的关系及临床意义。方法144例患者根据冠状动脉造影结果分为冠状动脉粥样硬化性心脏病(冠心病,n=96)组和对照组(n=48),冠心病患者再根据临床症状、病变支数、Gensini积分分组,ELISA方法检测受试者Lp-PLA2水平,进行对比分析。结果冠心病患者血清Lp-PLA2水平显著高于对照组(P0.01);急性心肌梗死(AMI)组Lp-PLA2水平显著高于稳定型心绞痛(SAP)组、不稳定型心绞痛(UAP)组(P均0.01);不同病变支数组和Gensini积分组之间Lp-PLA2水平有显著性差异(P均0.01);冠心病Logistic回归分析结果示Lp-PLA2与冠心病独立相关,优势比为1.028～1.068。冠状动脉Gensini积分的多元逐步回归分析显示Lp-PLA2与冠脉积分独立相关,(P0.01)。结论Lp-PLA2是冠心病的独立危险因素之一,血清Lp-PLA2水平能反映冠状动脉粥样斑块的稳定性及冠状动脉病变的严重程度。     

血清超敏C-反应蛋白、视黄醇结合蛋白4及血浆结合珠蛋白水平在冠心病患者中的变化及其意义

目的探讨冠心病(CHD)患者血清超敏C-反应蛋白(hs-CRP)、视黄醇结合蛋白4(RBP4)及血浆结合珠蛋白(Hp)水平的变化及其临床意义。方法选取2014年2月至2017年2月广安市人民医院心血管内科经冠状动脉造影检查确诊的CHD患者140例作为CHD组,另选取同期在我院心血管内科住院的非CHD患者60例作为对照组。将CHD组患者根据临床表现分为3个亚组:急性心肌梗死(AMI)组(n=38)、不稳定型心绞痛(UAP)组(n=62)和稳定型心绞痛(SAP)组(n=40)。依据病变支数分为3个亚组:单支病变组(n=27)、双支病变组(n=54)和三支病变组(n=59)。检测各组患者的血清hs-CRP、RBP4、Gensini评分及血浆Hp水平,并分析各指标与病情严重程度的关系。采用SPSS 16.0软件进行数据处理。依据数据类型,组间比较分别采用t检验和x~2检验。相关性分析采用Pearson线性相关分析法。结果 CHD组患者的血清hs-CRP[(7.29±3.65)vs(2.84±1.16)mg/L]、RBP4[(49.64±8.32)vs(42.07±5.51)ng/ml]及血浆Hp[(95.26±19.14)vs(70.13±16.33)mg/L]水平均显著高于对照组(P0.05)。AMI亚组患者的血清hs-CRP、RBP4、Gensini评分及血浆Hp水平均显著高于SAP亚组和UAP亚组患者(P0.05);UAP亚组患者的血清hs-CRP、RBP4、Gensini评分及血浆Hp水平均显著高于SAP亚组患者(P0.05)。三支病变亚组患者的血清hs-CRP、RBP4、Gensini评分及血浆Hp水平均显著高于双支病变和单支比病变亚组患者(P0.05);双支病变亚组患者的血清hs-CRP、RBP4、Gensini评分及血浆Hp水平均显著高于单支病变亚组患者(P0.05)。CHD患者的Gensini评分与血清hs-CRP(r=0.619)、RBP4(r=0.554)及血浆Hp(r=0.592)水平均呈显著正相关(P0.05)。结论 CHD患者血清hs-CRP、RBP4及血浆Hp水平显著升高,且与冠状动脉病变严重程度密切相关。     

心型脂肪酸结合蛋白与急性冠脉综合征患者冠状动脉病变程度的关系

目的探讨心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)与近期发作急性冠脉综合征患者的冠状动脉病变严重程度的相关性及原因分析。方法入选暨南大学医学院附属第四医院急性冠脉综合征(发作12 h内)患者168例,其中急性心肌梗死86例、不稳定型心绞痛82例。采用双抗体夹心酶联免疫吸附试验(ELISA)法检测血清H-FABP、肌钙蛋白(cardiac troponin T,CTnT)及肌酸磷酸激酶同工酶(creatine phosphokinase isoenzyme,CK-MB)浓度。采用Gensini积分系统对冠状动脉血管病变狭窄程度、病变部位及范围进行定量评定。比较急性心肌梗死组与不稳定型心绞痛组血清H-FABP浓度及冠状动脉病变Gensini积分;比较Gensini积分、冠状动脉狭窄程度、病变支数亚组之间H-FABP浓度;采用直线回归分析方法分析血清H-FABP浓度与冠状动脉病变严重程度、血清cTnT浓度、血清CK-MB浓度的相关性。结果急性心肌梗死组血清H-FABP浓度显著高于不稳定型心绞痛组,差异有统计学意义[(88.5±32.9)pg/mL vs.(14.3±5.4)pg/mL,P<0.01]。随着冠状动脉狭窄程度加重、累及支数增加及Gensini积分增加,血清H-FABP浓度显著升高,差异有统计学意义(P<0.05)。血清H-FABP浓度与cTnT(r=0.627,P<0.05)及CK-MB(r=0.530,P<0.05)具有相关性;与患者冠状动脉病变严重程度呈正相关(r=0.538,P<0.01),其相关系数高于cTnT与冠状动脉病变严重程度的相关性(r=0.385,P<0.05)。结论血清H-FABP浓度升高反映了冠状动脉病变严重程度,临床可根据血清H-FABP浓度升高推断冠状动脉病变的严重程度,并采取积极的治疗措施。     

Circulating soluble LR11, a novel marker of smooth muscle cell proliferation,is enhanced after coronary stenting in response to vascular injury

Objective

Restenosis after vascular intervention remains a major clinical problem. Circulating LR11 has been shown a novel marker of intimal smooth muscle cell (SMC) proliferation in human and animal studies. The present study was performed to clarify the clinical significance of circulating LR11 in patients with stable angina pectoris after coronary stenting.

Methods and results

We firstly investigated the circulating sLR11 levels for 28 days after arterial injury in mice, and then assessed time-dependent change in circulating sLR11 level after coronary stenting in a clinical study. Mouse sLR11 levels rapidly increased to 4.0-fold of the control value without cuff placement at postoperative day (POD) 14, and the levels gradually declined to 3.1-fold of the control value until POD 28 in mice. The circulating soluble LR11 levels were measured (before and at 14, 60 and 240 days after coronary stenting in a clinical study of 102 consecutive patients with stable angina pectoris who were treated with percutaneous coronary intervention. Circulating sLR11 levels were significantly increased on days 14 and 60 after the procedure and positively associated with the angiographic late loss index.

Conclusions

Our study suggested that circulating sLR11 levels may be a potential marker for angiographic late loss in patients after coronary stenting. Further mechanistic studies are expected to know the clinical significance of sLR11 as a novel marker for intimal SMC.     

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes.

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.     

Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis

OBJECTIVE: To analyze S-100 protein expression, in the form of myeloid-related protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP antigen expression in PsA patients. METHODS: Serum, synovial fluid (SF), and synovium (taken at arthroscopy) samples were obtained from PsA (before and after MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and SF were measured by enzyme-linked immunosorbent assay. Expression of MRP8, MRP14, and MRP8/MRP14 in synovium was determined by immunohistochemistry. RESULTS: MRP8, MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA, RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed significantly higher MRP8/MRP14 levels in SF (mean +/- SD 15310 +/- 16999 ng/ml [median 11400]) than in serum (908 +/- 679 ng/ml [median 695]) (P = 0.0001). MRP8/MRP14 levels in serum correlated with systemic parameters of disease activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C-reactive protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with local parameters of disease activity (white blood cell count r = 0.45, P = 0.01; acute-phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was significantly higher in the synovial sublining layer (SLL) of PsA patients compared with RA and SpA patients. MRP antigens were predominantly expressed in perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP expression in serum and synovium from PsA patients was significantly reduced. Serum levels of MRP were more sensitive to the effects of MTX than were the ESR, CRP, or clinical joint scores. CONCLUSION: MRP levels in serum and SF correlate with local and systemic inflammation and are equally increased in PsA, RA, and SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of PsA patients is increased, particularly in perivascular regions, compared with that in RA and SpA patients, suggesting a central role of MRP proteins in transendothelial migration of leukocytes in PsA. Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis.     

Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile idiopathic arthritis

OBJECTIVE: An unsolved problem in juvenile idiopathic arthritis (JIA) is to identify patients at special risk for relapse. It is important to adjust anti-inflammatory and immunosuppressive therapy to the children's actual disease activity especially in times of remission. Our aim was to analyze if the serum levels of MRP8/MRP14 are reliable predictive markers for the risk of relapse in clinically inactive juvenile idiopathic arthritis. METHODS: Serum concentrations of MRP8/MRP14 were determined by ELISA and correlated with laboratory and clinical parameters for disease activity in patients with JIA. 29 patients with changing disease activity were followed up for a mean time of 2.9 years. Two groups of patients--one before relapse (mean 3.7 months) but without clinical signs of disease reactivation, and one in remission for 12 further months--were compared. RESULTS: MRP8/MRP14 serum levels in patients before relapses were significantly higher than the levels in patients in stable remission for one year (662 ng/ml versus 395 ng/ml; p < 0.05). Using a cut-off for MRP8/MRP14 of 450 ng/ml the likelihood ratio for relapse was 3.7 (positive predictive value 80%), while no differences were found for C-reactive protein and erythrocyte sedimentation rate between the two groups. CONCLUSION: MRP8/MRP14 correlate with individual disease activity in patients with JIA. Our data suggest that local disease activity may be present even months before flares become clinically apparent. Serum levels of MRP8/MRP14 can give a hint as to clinically occult disease activity, in this way helping to adjust therapy in times of low disease activity.     

Increased perivascular synovial membrane expression of myeloid‐related proteins in psoriatic arthritis

Objective

To analyze S‐100 protein expression, in the form of myeloid‐related protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP antigen expression in PsA patients.

Methods

Serum, synovial fluid (SF), and synovium (taken at arthroscopy) samples were obtained from PsA (before and after MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and SF were measured by enzyme‐linked immunosorbent assay. Expression of MRP8, MRP14, and MRP8/MRP14 in synovium was determined by immunohistochemistry.

Results

MRP8, MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA, RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed significantly higher MRP8/MRP14 levels in SF (mean ± SD 15,310 ± 16,999 ng/ml [median 11,400]) than in serum (908 ± 679 ng/ml [median 695]) (P = 0.0001). MRP8/MRP14 levels in serum correlated with systemic parameters of disease activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C‐reactive protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with local parameters of disease activity (white blood cell count r = 0.45, P = 0.01; acute‐phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was significantly higher in the synovial sublining layer (SLL) of PsA patients compared with RA and SpA patients. MRP antigens were predominantly expressed in perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP expression in serum and synovium from PsA patients was significantly reduced. Serum levels of MRP were more sensitive to the effects of MTX than were the ESR, CRP, or clinical joint scores.

Conclusion

MRP levels in serum and SF correlate with local and systemic inflammation and are equally increased in PsA, RA, and SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of PsA patients is increased, particularly in perivascular regions, compared with that in RA and SpA patients, suggesting a central role of MRP proteins in transendothelial migration of leukocytes in PsA. Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis.

     

红斑狼疮患者瘦素及可溶性瘦素受体检测的临床意义

目的探讨血清瘦素(Lp)和可溶性瘦素受体(sLR)与不同临床分型的红斑狼疮(LE)及系统性红斑狼疮(SLE)病情活动程度的关系。方法于2004年6月至2005年12月对中国医科大学附属第二医院和中国医科大学附属第一医院的39例LE患者,同年龄、性别、体重指数(BMI)均相匹配的31名健康人对照,采用放射免疫法和酶联免疫吸附实验(ELISA)检测血清Lp和sLR水平。结果(1)与正常对照相比较,LE患者血清Lp水平增高和sLR水平下降,差异有统计学意义(P<0.01),活动期SLE患者血清Lp水平增高和sLR水平下降尤为显著;但非活动期SLE、亚急性皮肤型红斑狼疮(SCLE)和盘状红斑狼疮(DLE)患者血清Lp和sLR水平差异无统计学意义(P>0.05)。(2)Lp与BMI呈正相关,与sLR呈负相关;SLE患者的病情活动程度与血清Lp水平呈正相关,与sLR水平呈负相关(P<0.01)。结论Lp和sLR水平异常可能与LE的发病密切相关。     

Enhanced expression of myeloid-related protein complex (MRP8/14) in macrophages and multinucleated giant cells in granulomas of patients with active cardiac sarcoidosis.

BACKGROUND: The myeloid-related protein complex (MRP8/14) is expressed in activated human macrophages and reported to be involved in the inflammatory process. The expression of MRP8/14 in patients with cardiac sarcoidosis and idiopathic dilated cardiomyopathy (DCM) was investigated. METHODS AND RESULTS: Serum MRP8/14 levels were measured in 35 patients with sarcoidosis and 23 patients with DCM. Sera from 30 normal volunteers served as controls. Additionally, the expression profiles of MRP8/14 in the myocardium from 12 patients with active cardiac sarcoidosis and 10 DCM patients were examined immunohistochemically. Serum MRP8/14 levels were significantly higher in patients with sarcoidosis than in normal controls [515+/-549 (SD) ng/ml vs 230+/-115 ng/ml, p=0.0019]. In the sarcoidosis group, serum MRP8/14 levels in patients with definite cardiac involvement (n=10) were significantly higher than in those without (n=25) (974+/-878 ng/ml vs 332+/-204 ng/ml, p=0.0227) and they were also higher than in DCM patients (vs 252+/-108 ng/ml, p=0.0026). Immunohistochemically, MRP8/14 was specifically positive in the cytoplasm of macrophages and multinucleated giant cells in the myocardial granulomas. CONCLUSIONS: MRP8/14 may be involved in the pathogenesis of sarcoid granulomas. The measurement of serum MRP8/14 levels is useful for the diagnosis of sarcoidosis, and their higher levels suggest the cardiac involvement.     

Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation

OBJECTIVES: To determine whether myeloid related proteins (MRP8/MRP14), a complex of two S100 proteins related to neutrophil and monocyte activation, might be used as a marker for disease activity, and as an early indicator of relapse in juvenile idiopathic arthritis. PATIENTS AND METHODS: A group of 12 patients who underwent an autologous haematopoietic stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA) were studied. MRP8/MRP14 serum concentrations were determined by a sandwich enzyme linked immunosorbent assay (ELISA) as described. Improvement from baseline was described by a definition of improvement employing a core set of criteria as detailed previously by Giannini. RESULTS: After ASCT, MRP8/MRP14 serum concentrations in JIA showed a positive correlation with the Child Health Assessment Questionnaire (CHAQ; r=0.80) and erythrocyte sedimentation rate (r=0.45), but not with the total leucocyte count (r=0.26). Mean MRP8/MRP14 serum concentrations dropped markedly in the first three months after ASCT (p=0.0039) and clinical parameters of disease activity such as CHAQ markedly improved (p=0.0039). During a transient relapse there was an increase in MRP8/MRP14. CONCLUSIONS: MRP8/MRP14 serum concentration can be used as a marker for disease activity in patients who receive an ASCT for refractory JIA. This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration.     

Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease.

OBJECTIVES: This study investigated patients with acute Kawasaki disease (KD) to validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity and severity of coronary artery lesion development. BACKGROUND: Both MRP-8 and -14, which are S100-proteins secreted by activated neutrophils and monocytes, bind specifically to endothelial cells and induce thrombogenic and inflammatory responses in a variety of disease conditions. METHODS: We investigated 61 patients with acute KD and examined sequential changes in serum levels of MRP-8/MRP-14, messenger ribonucleic acid (mRNA) expression of MRP-8 and -14 in circulating granulocytes and monocytes, and amounts of MRP-8/MRP-14 bound to circulating endothelial cells. RESULTS: The serum MRP-8/MRP-14 levels as well as mRNA expressions of MRP-8 and -14 in granulocytes were strongly upregulated during the early stage of acute KD, and decreased dramatically within 24 h of intravenous immune globulin therapy (p < 0.05) in 45 responders. In contrast, in 16 nonresponders both of these increased after the initial treatment. The number of MRP-8/MRP-14-positive circulating endothelial cells was higher in patients with acute KD than in control patients and increased significantly by 2 weeks after the onset of KD, especially in patients in whom coronary artery lesions developed. CONCLUSIONS: We show for the first time that MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute KD, and intravenous immune globulin treatment suppresses their gene expression. Serum levels of MRP-8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP-14-positive circulating endothelial cell may predict the severity of vasculitis, confirming an important role for distinct inflammatory reactions in endothelium.     

Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis

OBJECTIVE: To analyze which physiologic stimuli induce secretion of myeloid-related protein 8 (MRP8) and MRP14, two S100 proteins expressed in neutrophils and monocytes, and to determine whether serum concentrations of these proteins are reliable parameters for monitoring inflammatory activity in pauciarticular juvenile rheumatoid arthritis (JRA). METHODS: Secretion of MRP8 and MRP14 was analyzed using a coculture system of endothelial cells and monocytes. Concentrations of MRP8/MRP14 in the serum and synovial fluid of JRA patients or culture medium were determined by enzyme-linked immunosorbent assay. The expression of MRP8 and MRP14 by leukocytes in synovial tissue or fluid was investigated using immunohistochemistry. RESULTS: MRP8 and MRP14 were specifically released during interaction of activated monocytes with tumor necrosis factor-stimulated endothelial cells. Secretion was mediated via an increase in intracellular calcium levels in monocytes. In contrast, contact with resting endothelium inhibited protein kinase C-induced secretion of the proteins by monocytes. In JRA patients, MRP8 and MRP14 were strongly expressed in infiltrating neutrophils and monocytes within the inflamed joints and could be found in significantly higher concentrations in synovial fluid (mean 42,800 ng/ml) compared with serum (2,060 ng/ml). Concentrations of MRP8/MRP14 in serum correlated well with those in synovial fluid (r = 0.78) and showed a strong correlation with disease activity (r = 0.62). After intraarticular triamcinolone therapy, the serum concentrations of MRP8/MRP14 decreased significantly in therapy responders, whereas no differences were found in patients who showed no clinical benefit. CONCLUSION: MRP8 and MRP14 are specifically released during the interaction of monocytes with inflammatory activated endothelium, probably at sites of local inflammation. Their serum concentrations represent a useful marker for monitoring local inflammation in JRA.