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단백분석을 통해 전신홍반루푸스의 잠재적 생물표지자로서 확인된 타액 내 단백의 특성화

초록/요약

Objectives: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by pathogenic autoantibodies and uncontrolled inflammatory response. There are few reliable biomarkers available for diagnosis and monitoring the disease. We tried to find and characterize specific protein components in saliva of patients with SLE for their use as biomarkers in future. Material and Methods: Salivary proteins were prepared from 11 samples from patients with SLE and healthy controls (HC), and were subjected to 2-dimensional gel electrophoresis (2-DE). The spots with greater than 2 fold change in intensity were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MS) analysis. The relative and absolute amounts of the several candidate proteins in saliva of patients with SLE and rheumatoid arthritis (RA) and HC were analyzed using western blotting and enzyme-linked immunosorbent assay. Results: Proteomic analysis using 2-DE and MS identified 20 differentially expressed protein spots in the saliva of SLE patients compared in that of HC. Among them, proteins with more than two-fold differences in expression were found as immunoglobulin gamma-3 chain C (IGHG3), immunoglobulin alpha-1 chain C region, protein S100, lactotransferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. salivary IGHG3 levels were increased in SLE (3.0 ± 1.4 pg/mL) compared to those in RA (1.5 ± 0.7 pg/mL, p < 0.001) or HC (1.2 ± 0.5 pg/mL, p < 0.001), and salivary lactotransferrin levels were increased in SLE (5.0 ± 1.7 pg/mL) compared to those in RA (3.1 ± 1.6 pg/mL, p < 0.001) or HC (2.3 ± 1.7 pg/mL, p < 0.001). Salivary lactotransferrin levels were correlated with complement 3 (r = 0.27, p = 0.01) and complement 4 (r = 0.27, p = 0.02). The follow up study, the patient with increased salivary IGHG3 had significantly different in changes of hemoglobin (-0.85 ± 0.87 vs 0.42 ± 0.99 /μL, p = 0.02) and changes of complement 3 (-7.67 ± 14.15 vs 7.0 ± 9.34, p = 0.02) compared to those not. In addition, the patients with increased salivary lactotransferrin had significantly different in changes of ESR (-2.0 ± 4.6 vs 8.4 ± 9.56, p = 0.02) compared to those not, and salivary lactotransferrin levels negatively correlated with complement 3 levels (r = -0.5, p= 0.02). Conclusion: Salivary IGHG3 and lactotransferrin levels were significantly increased in patients with SLE compared to those in patients with RA or HC, and could be used as potential biomarkers of SLE.

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목차

I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
Ⅲ. RESULTS 12
Ⅳ. DISCUSSION 24
V. REFERENCES 29
국문요약 36

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