川崎病患儿外周血基质金属蛋白酶1的表达及其与冠状动脉损伤的关系

目的观察基质金属蛋白酶1（matrix metalloproteinase-1,MMP-1）在川崎病患儿外周血不同时期的表达水平,探讨其在冠状动脉（简称冠脉）损伤中的作用。方法40例川崎病患儿（无冠脉损伤组23例,冠脉损伤组17例）,按病程分为急性期、亚急性期和恢复期;另分别以10例败血症患儿、10例健康儿童为发热对照组和正常对照组。应用酶联免疫吸附法检测血清MMP-1蛋白水平、逆转录聚合酶链反应（RT-PCR）检测外周血白细胞MMP-1 mRNA表达水平。结果急性期有、无冠脉损伤组血清MMP-1和白细胞表达MMP-1 mRNA水平均明显高于发热对照组和正常对照组（均P〈0．01）,且冠脉损伤组MMP-1蛋白和mRNA水平较无冠脉损伤组升高更为显著（P〈0．05）;到亚急性期、恢复期时MMP-1蛋白和mRNA水平依次明显降低（各期间比较,均P〈0．01）。川崎病组急性期血清MMP-1蛋白水平与外周血白细胞计数呈显著正相关（r=0．750,P〈0．01）。结论MMP-1在川崎病急性期,尤其在冠脉损伤时表达明显升高;MMP-1的过度表达可能与川崎病冠脉损伤的形成有关。     

人血丙种球蛋白对川崎病血清诱导血管内皮细胞表达基质金属蛋白酶-9的影响

目的　观察川崎病患儿急性期血清对血管内皮细胞表达基质金属蛋白酶- 9(MMP- 9)的影响及人血丙种球蛋白对上述过程的调节作用。方法　血管内皮细胞 (ECV- 30 4 )培养分为单独培养组、正常血清组、川崎病血清组、川崎病血清 人血丙种球蛋白组。应用明胶酶谱法、ELISA测定细胞培养上清中MMP 9活性和蛋白水平 ,RT- PCR法测定MMP 9mRNA表达。结果　川崎病血清组MMP- 9活性、蛋白浓度及mRNA表达水平均较单独培养组和正常血清组明显升高 (P <0 .0 1 ) ;而人血丙种球蛋白能显著抑制川崎病血清的上述诱导作用 (P <0 .0 1 )。结论　川崎病患儿急性期血清能诱导血管内皮细胞表达MMP -9增加 ,可能参与川崎病患儿冠状动脉损伤的发生 ;人血丙种球蛋白防治冠状动脉损伤机制 ,可能与抑制内皮细胞表达MMP- 9有关。     

川崎病患儿血清基质金属蛋白酶-1表达的意义

目的 探讨基质金属蛋白酶-1(MMP-1)在川崎病(KD)患儿冠状动脉损伤中的作用.方法 选择KD患儿36例(其中无冠状动脉损伤组15例,冠状动脉损伤组21例),按病程分为急性期、亚急性期和恢复期;10例健康儿童为健康对照组.应用酶联免疫吸附法检测其血清MMP-1蛋白水平.结果 KD急性期患儿血清MMP-1水平明显高于健康对照组(Pa＜0.01),且冠状动脉损伤组较无冠状动脉损伤组升高更显著(P＜0.05);亚急性期、恢复期其MMP-1水平明显降低(各期间比较Pa＜0.01).KD组急性期血清MMP-1水平与外周血白细胞计数呈显著正相关(r＝0.791 P＜0.01).结论 检测血清MMP-1水平对预测和早期诊断KD并冠状动脉病变具有重要意义.     

川崎病患儿急性期外周血Th9细胞与细胞因子IL-9的变化及临床意义

目的探讨辅助性T细胞9(Th9)及其细胞因子白细胞介素-9(IL-9)在川崎病(KD)患儿急性期外周血的表达及临床意义。方法选取2014年4月至2015年7月45例急性期川崎病患儿进行研究,并且对其进行恢复期随访;另取健康体检儿童45例作为对照组。采用流式细胞术检测外周血Th9水平及酶联免疫吸附试验(ELISA)检测血清IL-9水平。结果 KD患儿急性期Th9及IL-9水平明显高于恢复期和对照组(P0.05);而恢复期患儿与对照组的Th9、IL-9水平差异均无统计学意义(P0.05)。急性期的Th9与CRP、PCT、ESR、PLT及球蛋白水平呈正相关(r=0.324、0.402、0.382、0.467、0.386,均P0.05),与血清白蛋白呈负相关(r=-0.306;P0.05);IL-9水平与CRP、PCT、ESR、PLT、球蛋白水平呈正相关(r=0.365、0.456、0.403、0.423、0.453,均P0.05),与血清白蛋白呈负相关(r=-0.343;P0.05)。结论 KD患儿急性期外周血Th9细胞及其细胞因子IL-9水平明显升高,恢复期降至正常;且Th9表达及IL-9水平与急性期指标密切相关。推测Th9细胞与IL-9在KD的发病及转归过程起重要作用。     

IL-13鳞状细胞癌抗原及IgE在儿童咳嗽变异性哮喘中的检测价值

目的　咳嗽变异性哮喘是一种与白细胞介素 13(IL 13)相关的以气道炎症为特征的疾病。研究表明 ,IL 13所诱导的基因中鳞状细胞癌抗原 (SccAg)表达最多 ,因此推测SccAg在咳嗽变异性哮喘中的发病中也起重要作用。本文旨在评价IL 13、SccAg及免疫球蛋白E(IgE)在咳嗽变异性哮喘患儿中的检测价值。 方法　用酶联免疫吸附试验 (ELISA)法检测 5 1例咳嗽变异性哮喘患儿、2 6例哮喘患儿、33例正常儿童血清IL 13、SccAg及IgE水平 ,并对结果进行统计学处理。 结果　①咳嗽变异性哮喘患儿发作期血清IL 13(2 38.88± 4 0 .0 7ng/L)、SccAg (2 .81± 0 .38ng/ml)水平显著高于缓解期 (85 .15± 17.98ng/L,2 .2 9± 0 .31ng/ml)及正常对照组 (77.2 7±18.16ng/L,2 .2 9± 0 .34ng/ml) (均P <0 .0 1) ,但缓解期及正常对照组间差异无显著性 ;②咳嗽变异性哮喘发作期患儿血清IgE (6 2 2 .4 8± 2 95 .0 1KU/L)水平显著高于缓解期 (373.81± 15 7.92KU/L) ,两组均显著高于正常对照组 (10 2 .99± 38.81KU/L) (均P <0 .0 1) ;③咳嗽变异性哮喘患儿发作期血清IL 13、SccAg及IgE水平与哮喘患儿发作期 (2 6 3.12± 4 9.99ng/L ,3.0 1± 0 .37ng/ml,717.0 4± 314 .0 1KU/L)间差异无显著性。结论　联合检测血清IL 13、SccAg及IgE水     

抗β2糖蛋白1抗体、基质金属蛋白酶9与川崎病相关性及临床意义

目的 观察川崎病急性期患儿血清抗β2糖蛋白1(β2GP1)抗体、基质金属蛋白酶9(MMP-9)水平,探讨其与川崎病相关性及临床意义.方法 采用ELISA法检测47例川崎病患儿血清抗β2GP1抗体、MMP-9水平,应用SPSS11.5软件进行数据分析.30例同期住院、年龄相仿的感染性疾病患儿为发热对照组,均除外心、肝、肾、血液及风湿性疾病.结果 47例川崎病患儿中并发冠状动脉病变者17例.川崎病组和对照组血清中抗β2GP1抗体水平分别为(7.46±2.13)U/ml和(4.38±0.43)U/ml;MMP-9分别为(886.62 ±92.72)ng/ml和(460±179.59)ng/ml,两组比较差异均有统计学意义(P均<0.05);川崎病组中冠状动脉损伤与冠状动脉正常患儿血清抗β2GP1抗体分别为(8.83±0.89)U/ml和(6.18±1.42)U/ml,MMP-9分别为(948.62±81.76)ng/ml和(872.00±34.74)ns/ml,两组比较差异均有统计学意义(P均<0.05);川崎病组血清中抗β2CP1抗体、MMP-9水平呈显著正相关(r=0.665,P<0.05).结论 抗β2GP1抗体、MMP-9在川崎病急性期尤其伴冠状动脉病变时明显升高,两者在川崎病发生、发展过程中具有协同作用,是川崎病冠状动脉损伤血清学重要指标.     

P选择素及E选择素在小儿川崎病血管损伤中的作用机制及其意义

目的探讨P选择素(P-selectin, PS)、E选择素(E-selectin, ES)在小儿川崎病血管损伤中的作用机制,寻找其与冠状动脉(简称冠脉)损伤之间直接关系的依据.方法应用酶联免疫吸附实验(ELISA)双抗体夹心法、放免法检测36例川崎病(KD)患儿、20例发热疾病患儿、30例健康对照组儿童的PS、ES、血栓素(TXB2)、6酮前列腺素F1α(6-KPGF1α),并将KD患儿分为急性期、亚急性期、恢复期;有冠脉损伤(CAL)组与无冠脉损伤(NCAL)组,根据初始应用静脉丙种球蛋白(IVIG)48小时是否热退分为IVIG有效组与IVIG无效组.结果 KD患儿组的PS、ES急性期[ (211±28、186±14)ng/ml ]、亚急性期[(238±27、151±13)ng/ml]和恢复期[(198±21、100±9) ng/ml]均高于健康对照组 [(102±36、72±10)ng/ml],差异有显著性(P<0.01);治疗后PS仍维持较高水平,但IVIG有效组PS、ES下降与急性期相比差异有显著性(P<0.01);CAL组PS、ES[(281±78、210±52)ng/ml]水平明显高于NCAL组[(217±15、108±10)ng/ml,P<0.01 ],IVIG有效组PS、ES水平治疗后2周比治疗后1周降低,差异有显著性(P<0.01),IVIG无效组PS水平治疗后2周仍高于治疗后 1周,但差异无显著性(P>0.05);治疗后1周IVIG无效组与IVIG有效组PS水平未降低,差异无显著性(P>0.05);治疗后2周IVIG无效组PS、ES水平仍显著高于IVIG有效组(P<0.01),差异有显著性,PS的高峰期在亚急性期.KD患儿急性期TXB2水平显著升高,与健康对照组相比差异有显著性(P<0.01),亚急性期与正常组、CAL与NCAL组间差异无显著性(P>0.05),治疗后TXB2水平迅速降低;6-KPGF1α急性期、亚急性期、恢复期水平显著低于健康对照组(P<0.01);治疗后2周仍未达正常水平,CAL与NCAL组间差异无显著性(P>0.05);发热疾病组急性期PS、ES水平与健康对照组相比差异无显著性(P>0.05);KD组患儿ES与CRP水平差异有极显著性(r＝0.79 ,P<0.01),发热疾病组ES与CRP水平差异无显著性,KD组患儿PS与血小板计数(PLT)水平差异有极显著性(r＝0.75 ,P<0.01),发热疾病组PS与PTL差异无显著性.结论 PS、ES水平在KD患儿组急性期和亚急性期升高可能在川崎病患儿血管损伤的病理生理发生机制中起重要作用,PS、ES具有预示KD患儿CAL潜在的可能性.     

内皮素-1在新生儿缺氧缺血性脑病中的变化及意义

目的　探讨内皮素 - 1(ET - 1)在新生儿缺氧缺血性脑病 (HIE)中的变化及意义。方法　采用放射免疫法测定 2 0例正常小儿和 5 2例HIE患儿的血清及脑脊液 (CSF)中ET 1水平 ,并将HIE患儿分为轻、中、重 3组。结果　正常对照组血清ET 1为 6 8.71± 12 .0 3ng/L。轻、中、重度HIE血清ET 1在急性期分别为 98.38±12 .82ng/L ,10 7.2 1± 18.5 6ng/L ,119.5 6± 14.6 9ng/L ;恢复期分别为73.44± 11.79ng/L ,75 .73± 11.38ng/L ,83.92± 15 .99ng/L。HIE患儿急性期血清ET 1水平显著高于恢复期及正常对照组 ,P <0 .0 1。轻、中、重度HIE患儿急性期CSF中ET 1水平分别为 43.79± 7.14ng/L ,5 1.0 7± 11.19ng/L ,6 1.86± 13.5 5ng/L ;恢复期CSF中ET 1水平分别为 30 .79± 4.42ng/L ,33.0 7± 4.84ng/L ,39.5 0± 5 .5 6ng/L。急性期CSF中ET 1水平显著高于恢复期 ,均P <0 .0 1,且血清及CSF中ET 1水平与病情轻重密切相关。急性期HIE患儿血清和CSF中ET 1水平 ,重度组明显高于正常对照组P <0 .0 1及P <0 .0 5 ,尤以重度组升高显著 ;恢复期轻 ,中度组ET 1水平降至正常 ,而重度组仍维持在较高水平 ,且血清及CSF中ET 1水平与病情轻重密切相关。血清和CSF中ET 1水平与 1分钟Apgar评分呈显著负相关。 结论　ET 1在HIE的发     

新生儿缺氧缺血性脑病血清IL-8水平变化研究

目的　白细胞介素 8(IL 8)为缺血 /再灌注时炎症细胞的释放产物 ,并可引起细胞损伤。该研究旨在探讨IL 8是否参与新生儿缺氧缺血性脑病 (HIE)脑缺血 /再灌注损伤。方法　采用双抗体夹心ELISA法检测5 0例HIE患儿 (HIE组 ,其中轻度HIE 1 8例 ,中度HIE 1 7例 ,重度HIE 1 5例 ;合并感染者 2 9例 ,未合并感染者 2 1例 )、30例正常新生儿 (正常对照组 )及 2 0例患感染性疾病无HIE患儿 (感染组 )血清IL 8水平 ,HIE患儿经治疗后复查血清IL 8。结果　HIE组血清IL 8水平高于对照组 (2 1 .5 2± 9.5 9pg/mlvs 1 4 .4 3± 4 .84 pg/ml) ,差异有显著性 (P <0 .0 1 ) ;重度HIE患儿血清IL 8水平高于轻度HIE组 (2 6 .0 7± 1 3.83pg/mlvs 1 7.5 6± 6 .5 2pg/ml) ,差异有显著性 (P <0 .0 5 ) ,与中度HIE组比较 (2 1 .71± 5 .6 5 pg/ml) ,差异无统计学意义 (P >0 .0 5 ) ;HIE患儿治疗后IL 8水平较治疗前下降 (1 4 .5 3± 4 .87pg/mlvs 2 2 .6 0± 7.0 6 pg/ml) ,差异有显著性 (P <0 .0 1 ) ;有感染合并症HIE患儿血清IL 8水平高于无感染合并症患儿及感染组患儿依次为 2 3.79± 1 1 .0 4pg/ml,1 8.38± 6 .0 7pg/ml,1 8.2 2± 8.0 1 pg/ml,差异有显著性 (P <0 .0 5 )。结论　新生儿HIE时血清IL 8升高 ,病情越重升高越显著     

川崎病患儿急性期外周血单个核细胞NLRP3炎症小体的表达及其临床意义

目的 探讨Nod样受体蛋白3（NLRP3）炎症小体与川崎病（KD）患儿急性期炎症反应以及冠状动脉损伤的关系。方法 前瞻性纳入2017年1~10月住院的KD患儿42例为研究对象,其中伴冠状动脉损伤（CAL）9例,非冠状动脉损伤（NCAL）33例。另外选取性别、年龄相匹配的15例肺炎发热患儿作为发热对照组,15例健康儿童作为健康对照组。采用实时荧光定量PCR检测外周血单个核细胞NLPR3炎症小体（NLRP3、ASC和caspase-1） mRNA的表达。采用Spearman秩相关分析法评估NLRP3 mRNA表达与血清C反应蛋白（CRP）、红细胞沉降率（ESR）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、降钙素原、白蛋白及前白蛋白水平的相关性。结果 KD组急性期外周血NLRP3、ASC和caspase-1 mRNA表达明显高于发热对照组及健康对照组（P < 0.05）;CAL组患儿NLRP3 mRNA表达明显高于NCAL组（P < 0.05）。KD患儿急性期NLRP3 mRNA表达与CRP、IL-6、IL-1β、前白蛋白水平存在相关性（r_s分别为0.449、0.376、0.427、-0.416,均P < 0.05）。结论 NLRP3炎症小体可能参与了KD急性期炎症反应及CAL的发生。     

Soluble forms of the selectin family in children with Kawasaki disease: prediction for coronary artery lesions

AIM: To investigate the relationship between the plasma levels of soluble forms of the selectin family and the incidence of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: Thirty-three patients with KD, including group A patients (n = 22) who had no CALs and group B patients (n = 11) who had CALs, as well as age-matched febrile (n = 10) and afebrile controls (n = 11), were studied. RESULTS: Peak plasma E-selectin levels (172.0 +/- 58.6 ng ml(-1)) occurred during the acute phase of KD, while peak plasma P-selectin levels (260.3 +/- 43.2 ng ml(-1)) occurred during the subacute phase of the illness (p<0.05). Plasma L-selectin levels (1757.3 +/- 244.3 ng ml(-1)) during the convalescent phase tended to be higher than in either the acute or the subacute phase (not significant). Before intravenous immunoglobulin treatment, the plasma levels of E- (225.1 +/- 46.8 ng ml(-1)) and P-selectin (259.4 +/- 76.2 ng ml(-1)) of patients with CALs (n = 11) were significantly higher than those of patients (n = 22) with no CALs (E-selectin, 131.6 +/- 36.9 ng ml(-1); P-selectin, 184.9 +/- 84.6 ng ml(-1); p < 0.05). When a plasma E-selectin value before immunoglobulin treatment of >184.7 ng ml(-1) was used as the cut-off point, the sensitivity and specificity for the incidence of CALs were 81.8% and 90.9%, respectively. These findings demonstrate the relationship between plasma levels of selectins and disease severity of Kawasaki vasculitis. CONCLUSION: Higher plasma levels of E-selectin may have potential as a predictor of the incidence of coronary artery lesions in Kawasaki disease patients.     

Genetic analysis of MMP gene polymorphisms in patients with Kawasaki disease

Kawasaki disease (KD) is an acute febrile disorder characterized by systemic vasculitis primarily occurring in coronary arteries. Matrix metalloproteinases (MMPs) have been considered to play pathophysiologic roles in the development of coronary artery lesions (CALs); therefore, an evaluation of the genetic contributions of the MMP genes to the development of CALs in KD patients would be beneficial for the prediction of CAL formation. We focused on the known functional single nucleotide polymorphisms (SNPs) in the MMP genes (MMP-2-735C>T, MMP-3-1612 5A/6A, MMP-9-1562C>T, MMP-12-82A>G, and MMP-13-77A>G) and performed the association study between these SNPs and CAL formation in KD. The study population consisted of 44 KD patients with CALs and 92 without CALs and 175 healthy controls. As a result, allele and genotype frequencies of MMP-13-77A>G showed significant differences between KD patients with CALs and without CALs (p = 0.00989 and p = 0.00551, respectively). The estimated frequencies of the G-C haplotype in the MMP-13 gene promoter were significantly lower in KD patients with CALs than in those without CALs. There was no association between other MMP genes and CAL formation. In conclusion, the genetic evaluation by association study demonstrated that the MMP-13 gene, at least in part, contributed to the development of CALs in KD.     

Prediction of the risk of coronary arterial lesions in Kawasaki disease by serum 25-hydroxyvitamin D3

Kawasaki disease (KD) is associated with the development of coronary arterial lesions (CALs) in children. We aimed to test the hypothesis that circulating 25-hydroxyvitamin D₃ [25-(OH)D₃] could be identified as a clinical parameter for predicting CALs secondary to KD in children. We enrolled 35 children with KD in the acute phase and measured serum 25-(OH)D₃ levels in all of them, then followed up by echocardiography for CALs. Additionally, serum 25-(OH)D₃ levels were obtained in 23 febrile children with respiratory tract infections and 30 healthy children. Of the 35 KD children, nine had CALs according to echocardiography and 26 did not (NCALs). Serum 25-(OH)D₃ levels were not significantly different between NCALs and healthy children (49.2?±?23.8 versus 44.1?±?30.2 ng/ml; P?=?0.49). Serum 25-(OH)D₃ levels were significantly higher in children with CALs than those without CALs (83.9?±?26.3 versus 49.2?±?23.8 ng/ml; P?=?0.001). The cutoff value of 65 ng/ml to predict subsequent CALs had a specificity of 0.73, sensitivity of 0.78, and diagnostic accuracy of 0.74. Conclusion: Serum 25-(OH)D₃ levels were elevated dur-ing the acute phase in KD children who had subsequent CALs. Serum 25-(OH)D₃ levels in the acute phase of KD may be used to predict subsequent CALs.     

川崎病患儿血清MMP-9与TIMP-1质量浓度变化及其临床意义

目的探讨川崎病(KD)患儿血清基质金属蛋白酶-9(MMP-9)及其特异性组织抑制剂1(TIMP-1)质量浓度的变化在预测发生冠状动脉病变(CAL)风险中的临床意义。方法观察组为2003~2004年在四川大学华西第二医院与四川省人民医院住院的KD患儿32例,静脉注射丙种球蛋白(IVIG)前后各抽取患儿外周静脉血1次,同时抽取20名正常体检儿童(正常对照组)外周静脉血。ELISA双抗体法测定血清MMP-9与TIMP-1质量浓度。用二维超声心动图观察心脏冠状动脉病变。结果观察组患儿急性期血清MMP-9、TIMP-1质量浓度及MMP-9/TIMP-1比值均较正常对照组儿童显著增高(P<0.01);IVIG干预前CAL组患儿血清MMP-9质量浓度及血清MMP-9/TIMP-1显著地高于非CAL组患儿(P<0.01);IVIG干预后观察组患儿血清MMP-9质量浓度与MMP-9/TIMP-1显著降低(P<0.01);IVIG干预后CAL组患儿血清MMP-9质量浓度及血清MMP-9/TIMP-1仍显著高于非CAL组患儿(P<0.05),而后者MMP-9/TIMP-1基本降至正常儿童水平;观察组患儿血清TIMP-1质量浓度在IVIG干预前后无显著变化。结论MMP-9与TIMP-1可作为KD合并CAL的一种关联因素,动态监测血清MMP-9质量浓度和(或)MMP-9/TIMP-1比值对预测KD并发CAL具有较重要临床意义。     

基质金属蛋白酶9及组织抑制物1对预测和早期诊断川崎病冠状动脉病变的意义

目的探讨川崎病（Kawasaki disease,KD）血清基质金属蛋白酶9（matrix metallopmteinase-9,MMP-9）及其特异性组织抑制物1（tissue inhibitor of metalloproteinase-1,TIMP-1）水平的动态变化在冠状动脉病变（coronary artery lesion,CAL）的预测和早期诊断中的临床价值。方法实验组KD合并CAL患儿15例,未合并CAL患儿44例,急性期静脉注射免疫球蛋白（intravenous immunoglobulin,IVIG）前后、亚急性期及恢复期各抽取1次外周静脉血,对照组为20例正常体检儿童。ELISA双抗体法测定血清MMP-9与TIMP-1含量。结果KD患儿急性期血清MMP-9含量、TIMP-1含量及MMP-9／TIMP-1均较正常对照组增高（P〈0、01）;IVIG干预后KD患儿血清MMP-9含量与MMP-9／TIMP-1比值降低（P〈0．01）;KD合并CAL患儿IVIG干预前血清MMP-9含量及血清MMP-9／TIMP-1比值高于无CAL患儿（P〈0．01）。结论川崎病冠状动脉病变患儿血清MMP-9含量与MMP-9／TIMP-1比值在急性期高于无冠状动脉病变患儿,提示MMP-9含量的急剧升高及与TIMP-1相互拮抗作用的失代偿可能是川崎病冠状动脉病变的高风险因素,动态监测血清MMP-9含量和（或）MMP-9／TIMP-1比值对预测和早期诊断川崎病合并冠脉病变具有重要的临床意义。     

Extracellular matrix turnover and disease severity in Anderson–Fabry disease

Background: Anderson–Fabry disease (AFD) is an inherited metabolic disease associated with premature death from cardiovascular and renal disease. Recent studies have shown that patients with AFD develop progressive left-ventricular (LV) remodelling. We hypothesized that patients with AFD have abnormal extracellular matrix (ECM) turn over compared with normal controls.
Methods and Results: Twenty-nine (mean age (±SD), 44.1±11.7 years; 15 male) consecutive patients with AFD and 21 age- and gender-matched controls (mean age, 39.7±11.3 years; 10 male) had serum analysed for matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP)-1 and -2 levels using an in-house enzyme-linked immunosorbent assay. MMP-9 levels were significantly elevated in patients compared with controls (mean difference from controls, 427.1 ng/ml, 95% CI, 252.1 – 602.2 ng/ml, p <0.001). There was a negative correlation between MMP-9 and fractional shortening (r = − 0.5, p =0.01). There were no differences in TIMP levels between patients and controls. There was no correlation between LV mass or maximal LV wall thickness and MMP-9 levels. There was a positive correlation between MMP-9 levels and the Mainz Severity Score Index (r = 0.5, p =0.01). These relationships remained significant, independently of gender and age-using stepwise linear regression analysis.
Conclusion: Patients with AFD have higher levels of MMP-9 compared with controls. MMP-9 levels correlated with clinical markers of disease severity suggesting that abnormal ECM turnover plays an important role in the pathogenesis of AFD. This in turn suggests that MMP-9 levels may be a useful circulating marker for disease severity and a surrogate marker for the response to enzyme replacement therapy.