Antibody profiling of bipolar disorder using Escherichia coli proteome microarrays

Abstract

To profile plasma antibodies of patients with bipolar disorder (BD), an E. coli proteome microarray comprising ca. 4200 proteins was used to analyze antibody differences between BD patients and mentally healthy controls (HCs). The plasmas of HCs and patients aged 18-45 years with bipolar I disorder (DSM-IV) in acute mania (BD-A) along with remission (BD-R) were collected. The initial samples consisting of 19 BD-A, 20 BD-R, and 20 HCs were probed with the microarrays. After selecting protein hits that recognized the antibody differences between BD and HC, the proteins were purified to construct BD focus arrays for training diagnosis committees and validation. Additional six BD-A, six BD-R, six HCs, and nine schizophrenic disorder (SZ, as another psychiatric control) samples were individually probed with the BD focus arrays. The trained diagnosis committee in BD-A versus HC combined top six proteins, including rpoA, thrA, flhB, yfcI, ycdU, and ydjL. However, the optimized committees in BD-R versus HC and BD-A versus BD-R were of low accuracy (< 0.6). In the single blind test using another four BD-A, four HC, and four SZ samples, the committee of BD-A versus HC was able to classify BD-A versus HC and SZ with 75% sensitivity and 80% specificity that both HC and SZ were regarded as negative controls. The consensus motif of the six proteins, which form the committee of BD-A versus HC, is [KE]DIL[AG]L[LV]I[NL][IC][SVKH]G[LV][VN][LV] by Gapped Local Alignment of Motifs. We demonstrated that the E. coli proteome microarray is capable of screening BD plasma antibody differences and the selected proteins committee was successfully used for BD diagnosis with 79% accuracy.