Autoantibody against one of the antioxidant repair enzymes, methionine sulfoxide reductase A, in systemic sclerosis: association with pulmonary fibrosis and vascular damage.
Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis and vascular changes in the skin and internal organs with autoimmune background. It has been suggested that oxidative stress plays an important role in the development of SSc. To determine the prevalence and clinical correlation of autoantibody to methionine sulfoxide reductase A (MSRA), one of the antioxidant repair enzymes, in SSc, serum anti-MSRA autoantibody levels were examined in patients with SSc by enzyme-linked immunosorbent assay using recombinant MSRA. The presence of anti-MSRA antibody was evaluated by immunoblotting. To determine the functional relevance of anti-MSRA antibody in vivo, we assessed whether anti-MSRA antibody was able to inhibit MSRA enzymatic activity. Serum anti-MSRA antibody levels in SSc patients were significantly higher compared to controls and this autoantibody was detected in 33% of SSc patients. Serum anti-MSRA levels were significantly elevated in SSc patients with pulmonary fibrosis, cardiac involvement, or decreased total antioxidant power compared with those without them. Anti-MSRA antibodies also correlated positively with renal vascular damage determined as pulsatility index by color-flow Doppler ultrasonography of the renal interlobar arteries and negatively with pulmonary function tests. Furthermore, anti-MSRA antibody levels correlated positively with serum levels of 8-isoprostane and heat shock protein 70 that are markers of oxidative and cellular stresses. Remarkably, MSRA activity was inhibited by IgG isolated from SSc sera containing IgG anti-MSRA antibody. These results suggest that elevated anti-MSRA autoantibody is associated with the disease severity of SSc and may enhance the oxidative stress by inhibiting MSRA enzymatic activity.
Ogawa
Fumihide
F
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Shimizu
Kazuhiro
K
Hara
Toshihide
T
Muroi
Eiji
E
Komura
Kazuhiro
K
Takenaka
Motoi
M
Hasegawa
Minoru
M
Fujimoto
Manabu
M
Takehara
Kazuhiko
K
Sato
Shinichi
S
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001808:Blood Vessels / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D056945:Hep G2 Cells; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D008297:Male; D051150:Methionine Sulfoxide Reductases / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000150:complications / Q000276:immunology*; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology*; D018617:Ultrasonography, Doppler, Pulsed
D001323:Autoantibodies; D018840:HSP70 Heat-Shock Proteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D051150:Methionine Sulfoxide Reductases