TY - JOUR
T1 - Isotypes of autoantibodies against differentially expressed novel malondialdehyde-modified peptide adducts in serum of Taiwanese women with rheumatoid arthritis
AU - Liao, Chen Chung
AU - Chang, Yu Sheng
AU - Cheng, Chao Wen
AU - Chi, Wei Ming
AU - Tsai, Kai Leun
AU - Chen, Wei Jung
AU - Kung, Ting Shuan
AU - Tai, Chih Chun
AU - Lin, Yi Fang
AU - Lin, Hung Tse
AU - Lu, Yi Ying
AU - Lin, Ching Yu
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/1/6
Y1 - 2018/1/6
N2 - This study identified and validated four differentially expressed novel malondialdehyde (MDA)-modified peptide adducts and evaluated autoantibodies against native and MDA-modified peptides among Taiwanese women patients with rheumatoid arthritis (RA), osteoarthritis (OA) and healthy controls (HCs). Ig kappa chain C region76–99, alpha-1-antitrypsin284–298, alpha-2-macroglobulin824–841, and apolipoprotein B-1004022–4040 exhibiting 2-fold differences in relative modification ratios were identified by concanavalin A (Con A) affinity chromatography, 1D SDS-PAGE, in-gel digestion, nano-LC/MS/MS and nano-LC/MS using pooled serum-derived Con A-captured proteins from 9 RA and 9 age-matched HCs. Furthermore, the levels of proteins, serum MDA, and MDA-modified protein adducts were further validated against individual serum from 20 RA and 20 HCs, and autoantibodies against native and their MDA-modified peptides used 45 RA, 30 OA and 45 HCs. Levels of serum MDA and MDA-modified protein adducts were significantly higher in RA than HCs but protein levels were not significantly different. Serum Igs G and M against MDA-modified peptides showed better diagnostic performance in differentiating among patients with RA, OA and HCs, with an area under the receiver operating characteristic curve of 0.96–0.98, sensitivity of 88.9%–97.8%, and specificity of 88.9%–100%. Autoantibodies against MDA-modified epitopes become useful clinical biomarkers for RA. Biological significance By using a label-free relative quantitative proteomic analysis of concanavalin A (Con A)-bound serum samples, the current study discovered and validated malondialdehyde (MDA)-modified peptide adducts as novel biomarkers for differentiating between rheumatoid arthritis (RA) patients and healthy controls (HCs). In addition, the serum levels of MDA, proteins, and MDA-modified protein adducts as well as the MDA modification of proteins were determined. Isotypes of autoantibodies against MDA-modified peptide adducts can be used as serological biomarkers for further discriminating among RA patients, osteoarthritis patients and HCs. This strategy can become the basis for identifying potential diagnostic and pathological biomarkers for RA.
AB - This study identified and validated four differentially expressed novel malondialdehyde (MDA)-modified peptide adducts and evaluated autoantibodies against native and MDA-modified peptides among Taiwanese women patients with rheumatoid arthritis (RA), osteoarthritis (OA) and healthy controls (HCs). Ig kappa chain C region76–99, alpha-1-antitrypsin284–298, alpha-2-macroglobulin824–841, and apolipoprotein B-1004022–4040 exhibiting 2-fold differences in relative modification ratios were identified by concanavalin A (Con A) affinity chromatography, 1D SDS-PAGE, in-gel digestion, nano-LC/MS/MS and nano-LC/MS using pooled serum-derived Con A-captured proteins from 9 RA and 9 age-matched HCs. Furthermore, the levels of proteins, serum MDA, and MDA-modified protein adducts were further validated against individual serum from 20 RA and 20 HCs, and autoantibodies against native and their MDA-modified peptides used 45 RA, 30 OA and 45 HCs. Levels of serum MDA and MDA-modified protein adducts were significantly higher in RA than HCs but protein levels were not significantly different. Serum Igs G and M against MDA-modified peptides showed better diagnostic performance in differentiating among patients with RA, OA and HCs, with an area under the receiver operating characteristic curve of 0.96–0.98, sensitivity of 88.9%–97.8%, and specificity of 88.9%–100%. Autoantibodies against MDA-modified epitopes become useful clinical biomarkers for RA. Biological significance By using a label-free relative quantitative proteomic analysis of concanavalin A (Con A)-bound serum samples, the current study discovered and validated malondialdehyde (MDA)-modified peptide adducts as novel biomarkers for differentiating between rheumatoid arthritis (RA) patients and healthy controls (HCs). In addition, the serum levels of MDA, proteins, and MDA-modified protein adducts as well as the MDA modification of proteins were determined. Isotypes of autoantibodies against MDA-modified peptide adducts can be used as serological biomarkers for further discriminating among RA patients, osteoarthritis patients and HCs. This strategy can become the basis for identifying potential diagnostic and pathological biomarkers for RA.
KW - Autoantibody isotypes
KW - Malondialdehyde
KW - Rheumatoid arthritis
KW - Serum
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U2 - 10.1016/j.jprot.2017.08.012
DO - 10.1016/j.jprot.2017.08.012
M3 - Article
AN - SCOPUS:85032305059
SN - 1874-3919
VL - 170
SP - 141
EP - 150
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -