Tissue proteome profiling of preeclamptic placenta using recombinant antibody microarrays

PURPOSE: preeclampsia (PE) is a severe, multi-system pregnancy disorder of yet unknown cause, missing means of treatment, and our fundamental understanding of the disease is still impaired. The purpose of this discovery study was to define candidate placenta tissue protein biomarker signatures to further decipher the molecular features of PE.

EXPERIMENTAL DESIGN: we used recombinant antibody microarrays for multiplexed protein expression profiling of preeclamptic placenta tissue (n=25) versus normal placenta (n=11) targeting mainly immunoregulatory water-soluble proteins and membrane proteins. Furthermore, the three known subgroups of PE were profiled, including women with early onset preeclampsia and late onset preeclampsia, as well as women with PE and bilateral notching and intrauterine growth restrictions.

RESULTS: the data showed that the first generation of candidate PE-associated placenta tissue protein signatures were delineated, indicating that PE (receiver operating characteristics (ROC) AUC value of 0.83) and the subgroups thereof (ROC AUC values ≤ 0.91) could be distinguished. Notably, the data implied that all subgroups, but preeclampsia with bilateral notching and IUGR, could be further classified into novel subsets (ROC AUC values of 1.0) displaying different inflammatory signatures.

CONCLUSIONS AND CLINICAL RELEVANCE: we have taken one step further toward de-convoluting the complex features of PE at the molecular level using affinity proteomics.