Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening Marker by Liquid Chromatography Tandem-mass Spectrometry

Molecules. 2017 May 14;22(5):805. doi: 10.3390/molecules22050805.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of RA prescreening. e identified differentially expressed proteins (DEPs) by using liquid chromatography tandem-mass spectrometry in health-prescreening sera with high rheumatoid factor (RF) values, and compared the findings with those from sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated, and 57 were downregulated in high-RF sera. Pathway analysis revealed that these DEPs were related to immune responses. Additionally, four DEPs were statistically analyzed by proteomic analysis; of these, SAA4 was significantly validated in individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly upregulated in RA patients (n = 40, 66.43 ± 12.97 ng/mL) compared with normal controls (n = 40, 4.79 ± 0.95 ng/mL) and had a higher area under the curve than C-reactive protein. Thus, we identified SAA4 as a protein that was positively correlated with RF and RA. SAA4 may represent a novel prescreening marker for the diagnosis of RA.

Keywords: LC-MS/MS; pre-screening; rheumatoid factor; serum amyloid A4.

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / metabolism*
  • Biomarkers / metabolism*
  • C-Reactive Protein / metabolism
  • Chromatography, Liquid / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteomics
  • Serum Amyloid A Protein / metabolism*
  • Tandem Mass Spectrometry / methods*

Substances

  • Biomarkers
  • SAA4 protein, human
  • Serum Amyloid A Protein
  • C-Reactive Protein