Molvarec Attila, Derzsy Zoltán, Kocsis Judit, Boze Tamás, Nagy Bálint, Balogh Krisztián, Makó Veronika, Cervenak László, Mézes Miklós, Karádi István, Prohászka Zoltán, Rigó János
1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
Cell Stress Chaperones. 2009 Sep;14(5):491-8. doi: 10.1007/s12192-009-0102-4. Epub 2009 Feb 11.
It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer's kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p < 0.001, respectively). However, no other relationship was found between clinical features (maternal age, smoking status, parity, body mass index, gestational age at blood draw, systolic and diastolic blood pressure, gestational age at delivery, and fetal birth weight) and measured laboratory parameters of the study subjects and serum anti-Hsp antibody levels in either study group. In conclusion, anti-Hsp60 and anti-Hsp70 antibodies as naturally occurring autoantibodies are present in the peripheral circulation of healthy pregnant women. Nevertheless, humoral immunity against heat shock proteins was not associated with preeclampsia. Further studies are warranted to explore the role of heat shock proteins and immune reactivity to them in the immunobiology of normal pregnancy and preeclampsia.
先前已有报道称,心血管疾病患者体内循环抗热休克蛋白(Hsp)抗体水平会升高。本研究的目的是测定健康孕妇和先兆子痫患者体内循环抗人Hsp60、抗分枝杆菌Hsp65和抗人Hsp70抗体水平,并研究它们与研究对象的临床特征以及炎症标志物(C反应蛋白(CRP))、内皮激活标志物(血管性血友病因子抗原)或内皮损伤标志物(纤连蛋白)、氧化应激标志物(丙二醛)以及血清Hsp70水平之间的关系。93例先兆子痫患者和127例血压正常的健康孕妇参与了这项病例对照研究。采用酶联免疫吸附测定(ELISA)法检测血清抗Hsp60、抗Hsp65、抗Hsp70和Hsp70水平。使用制造商提供的试剂盒通过自动分析仪测定血清CRP水平。采用ELISA法定量血浆血管性血友病因子抗原水平,采用散射比浊法测定血浆纤连蛋白浓度。采用基于硫代巴比妥酸的比色法测定血浆丙二醛水平。统计分析采用非参数方法。在我们所有的血清样本中均检测到抗Hsp60、抗Hsp65和抗Hsp70抗体。对照组和先兆子痫组血清抗Hsp60、抗Hsp65和抗Hsp70抗体水平无显著差异。先兆子痫患者血清Hsp70和CRP水平以及血浆VWF抗原、纤连蛋白和丙二醛水平均显著高于血压正常的健康孕妇。在对照组和先兆子痫组中,血清抗Hsp60抗体水平与血清抗Hsp65抗体水平均呈显著相关(Spearman相关系数R分别为0.55和0.59;p均<0.001)。然而,在任何一个研究组中,研究对象的临床特征(产妇年龄、吸烟状况、产次、体重指数、采血时的孕周、收缩压和舒张压、分娩时的孕周以及胎儿出生体重)与所测实验室参数和血清抗Hsp抗体水平之间均未发现其他相关性。总之,抗Hsp60和抗Hsp70抗体作为天然存在的自身抗体存在于健康孕妇的外周循环中。然而,针对热休克蛋白的体液免疫与先兆子痫无关。有必要进一步研究热休克蛋白及其免疫反应性在正常妊娠和先兆子痫免疫生物学中的作用。