The presence of maternal autoantibodies has been previously associated with preeclampsia, although the composition of the antibody repertoire in preeclampsia has not been well characterized. Given this, we applied a bacterial display peptide library to identify peptides that preferentially react with plasma antibodies from patients with preeclampsia (n=15) versus healthy-outcome pregnancies (n=18). Screening using fluorescence-activated cell sorting identified 38 peptides that preferentially bind to antibodies from individuals with preeclampsia. These preeclampsia-specific peptides possessed similar motifs of R(G)/S(G)/-WW(G)/S, RWW(G)/S, or WGWGXX(R)/K distinct from the angiotensin II type 1 receptor epitope AFHYESQ. Seven library-isolated peptides and a cell surface-displayed angiotensin II type 1 receptor epitope were used to construct a diagnostic algorithm with a training set of 18 new preeclamptic and 22 healthy-outcome samples from geographically distinct cohorts. Cross-validation within the training group resulted in averaged areas underneath a receiver operating characteristic curve of 0.78 and 0.72 with and without the known receptor epitope, respectively. In a small validation set (12 preeclamptic; 8 healthy), the algorithm consisting only of library-isolated peptides correctly classified 10 preeclamptic and 6 healthy samples using a predefined cutoff that achieved 61% sensitivity (95% confidence interval, 36%-83%) at 95% specificity (95% confidence interval, 77%-100%) in training set (n=40) cross-validation. Our results indicate that antibodies with specificities other than anti-angiotensin II type 1 receptor are prevalent in preeclampsia patients and may be useful as diagnostic biomarkers.
Keywords: antibodies; biological markers; diagnosis; peptide library; preeclampsia.