Prospective determination of heat shock protein serum levels in Saskatchewan women during pregnancy

BACKGROUND

The stress proteins, heat shock protein 27, heat shock protein 70, and αB-crystallin, have all been detected in human serum under normal and disease conditions. Heat shock protein 70 serum levels are known to increase in women with advancing pregnancy, but heat shock protein 27, heat shock protein 70, and αB-crystallin have never been assessed prospectively in pregnancy and labor.

OBJECTIVE

This study aimed to determine the serum levels of heat shock protein 27, heat shock protein 70, and αB-crystallin in women during pregnancy to assess whether the levels increase significantly over time and particularly at term and/or labor.

STUDY DESIGN

A prospective cohort pilot study of serum levels of heat shock protein 27, heat shock protein 70, and αB-crystallin in Saskatoon-area women with singleton pregnancies using enzyme-linked immunosorbent assays was conducted. Serum samples were collected from each patient at 3 periods: <14 weeks of gestation, 22 to 33 weeks of gestation at glucose screening, and at term nonlabor/active labor. The enzyme-linked immunosorbent assay data were subjected to D’Agostino and Pearson tests for normality. If data were not normally distributed, Friedman tests followed by Dunn multiple comparisons tests were performed. If data were normally distributed, they were subjected to repeated measures one-way analysis of variance, followed by Tukey multiple comparisons tests. In addition, a Spearman correlation analysis of heat shock protein levels with increasing gestational age was performed. All data were assessed and graphed using GraphPad Prism software.

RESULTS

Heat shock protein 27 levels were significantly elevated at term/labor compared with the 2 earlier time points assessed (Dunn multiple comparisons test: P<.0001 compared with <14 weeks of gestation and P=.0014 compared with 22–33 weeks of gestation). In addition, heat shock protein 70 serum levels were significantly elevated at term/labor compared with earlier time points (Dunn multiple comparisons test: P=.0005 compared with <14 weeks of gestation and P=.0179 compared with 22–33 weeks of gestation). In contrast, αB-crystallin levels were not significantly different throughout pregnancy. When the serum levels of the heat shock proteins throughout pregnancy were separately examined in the prospective cohorts who were sampled at term or at active spontaneous or induced labor, heat shock protein 27 levels were still significantly elevated at term (Tukey multiple comparisons test: P=.003 compared with <14 weeks of gestation and P=.031 compared with 22–33 weeks of gestation) or at labor (Tukey multiple comparisons test: P<.0001 compared with <14 and 22–33 weeks of gestation). Of note, heat shock protein 27 levels were significantly elevated at term compared with at labor (3.949±0.622 vs 2.139±0.241, respectively; Welch P=.0211). Heat shock protein 70 levels were only significantly elevated at term (Dunn P=.029) or at labor (Tukey P=.015) compared with <14 weeks of gestation. αB-crystallin levels were not significantly different throughout pregnancy in these 2 cohorts. Overall, there was a significant positive correlation between gestational age and heat shock protein 27 or heat shock protein 70 serum concentrations, regardless of whether term/labor was examined as a group or in separate cohorts of patients who were sampled at term or labor.

CONCLUSION

Serum levels of heat shock protein 27 and heat shock protein 70 in pregnant women at term and/or labor were significantly elevated relative to earlier periods of pregnancy, and serum levels positively correlated with gestational age. However, heat shock protein 27 levels were also significantly elevated at term compared with at labor, thereby identifying this small heat shock protein as a candidate biomarker of impending labor. Such a biomarker could be valuable for screening term pregnant women in rural settings who are distant from urban delivery centers to minimize travel, economic costs, and maternal stress.