Autoantibody Against one of the Antioxidant Repair Enzymes, Methionine Sulfoxide Reductase A (MSRA), in Systemic Sclerosis: Association with Pulmonary Fibrosis and Vascular Damage

抄録

Purpose: For protecting oxidative injuries, cell contains multiple antioxidant mechanisms. Methionine sulfoxide reductase A (MSRA) is one of the antioxidant enzyme peptides, which repairs oxidized methionine, methionine sulfoxide, into methionine. Recently, MSRA is suggested to play a protective role against oxidative stress including ischemic/hypoxic injury. Methods: Serum anti-MSRA autoantibody (Ab) levels were examined in 70 patients with SSc by ELISA. Results: Serum anti-MSRA Ab levels were significantly elevated in SSc patients compared to normal controls (mean ± SD; 0.70 ± 0.29, n=70 vs. 0.52 ± 0.15, n=23; p<0.01). Regarding the disease subset, anti-MSRA Ab levels were similar between patients with diffuse cutaneous SSc (n=40) and those with limited cutaneous SSc (n=30). Concerning clinical correlation, anti-MSRA Ab levels significantly increased in SSc patients with pulmonary fibrosis (p<0.05), cardiac involvement (p<0.05), or decreased total antioxidant power (p<0.05) compared with those without pulmonary fibrosis, cardiac disease, or decreased total anti oxidant power. Furthermore, anti-MSRA Ab levels correlated negatively with %VC (r=-0.37, p<0.05) and %DLco (r=-0.26, p<0.05), and positively with renal vascular resistance determined as the PI value (r=0.31, p<0.05). MSRA activity was significantly inhibited by anti-MSRA Ab in the serum of SSc patients. Conclusion: These results suggest that anti-MSRA Ab contributes to the development of the disease severity and activity in SSc by inhibiting one of the antioxidant repair enzymes, MSRA.