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Transthyretin as a potential serological marker for the diagnosis of patients with early rheumatoid arthritis.

OBJECTIVES
To investigate the serum levels and modifications of transthyretin (TTR) in patients with rheumatoid arthritis (RA) by mass spectrometry, and the potential role of TTR in early RA.


METHODS
Serum samples were collected from early RA (ERA), middle and late RA (LRA), osteoarthritis (OA) patients, and healthy controls (HC). Levels of TTR were measured by ELISA, and serum TTR was further detected by Western blot. A subsequent MALDI-TOF-MS was performed to analyse the modified TTR.


RESULTS
Serum TTR levels in ERA (502.46±108.15 mg/l) was significantly higher than that of healthy controls (424.98±117.63 mg/l) (p<0.05). TTR levels in LRA was higher than that of HC but without statistical significance (p>0.05), and no statistical significance between OA (363.90±105.21mg/l) and HC (p>0.05). Two protein bands were identified corresponding to monomer and dimmer TTR by western blot. The proportion of TTR monomer was similar in each group. However, the proportion of TTR dimer in RA was lower than that in HC, which was decreased more in LRA (p<0.05). By MALDI-TOF-MS, four major peaks were observed in sera corresponding to native TTR (13749.86±1.48 m/z), Sul-TTR (13829.63±2.76 m/z), Cys-TTR (13870.70±2.70 m/z), and Cysgly-TTR (13927±5.77 m/z). The proportion of modified TTR varied with different disease stages.


CONCLUSIONS
TTR levels in sera of patients with early RA were significantly increased. Four modified TTR were identified by MALDI-TOF-MS, and the proportion of modified TTR varied with different disease stages. Thus serum TTR could be considered as a potential serological marker for early diagnosis of RA.