Plasma proteomic screening and validation of novel biomarkers in Takayasu's arteritis

To screen and validate differential proteins as novel biomarkers in active Takayasu's arteritis (TAK).

Plasma samples from 40 active, 40 inactive patients, and 40 healthy controls were collected. Protein profiles of plasma were mapped by two-dimensional gel electrophoresis. Differential protein spots were detected and identified by image analysis and mass spectrometry. Plasma concentrations of proteins were measured to validate candidate biomarkers. The area under the receiver operating characteristic (ROC) curve (AUC) of circulating plasma concentrations of candidate biomarkers were calculated to assess diagnostic value.

With a total of 1507 matched gel spots, there were 170 differential expression spots between active and inactive TAK, including 139 up-regulated and 31 downregulated. Only 11 proteins could be identified by mass spectrometry. Serum amyloid A(SAA), fibrinogen, complement C4a, complement C3c, complement C4b binding protein(C4bp), recombination acting gene protein 1(RAG1), alpha-1-acid glycoprotein, alpha-1-microglobulin, complement C7, complement factor H related protein-1 were up-regulated in active patients, while serum amyloid P was down-regulated. Active patients had higher circulating levels of RAG1(P<0.001), C4bp (p=0.012) and SAA (p<0.001), compared to inactive patients, while inactive patients had higher levels than controls (RAG1, p=0.011; C4bp, p=0.012; SAA, p=0.005). The composite AUC with SAA, RAG1, and C4bp was 0.94 (95%CI 0.86-0.98) for discriminating activity, larger than 0.71(95% CI 0.60-0.80) for ESR (p=0.0004) or 0.75(95%CI 0.64-0.84) for CRP (p=0.0014), respectively.

Some acute-phase and immunology-related proteins may serve as novel biomarkers of TAK. Further study of these proteins may be helpful to elucidate the pathologic mechanism.