title: Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress.
abstract: OBJECTIVE
  To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc).
  
  
  METHODS
  Serum samples from SSc patients (n = 70) and healthy controls (n = 23) were examined by ELISA using human recombinant Prx I. The presence of anti-Prx I antibody was further evaluated by immunoblotting analysis. To determine the functional relevance of anti-Prx I antibody in vivo, we assessed whether anti-Prx I antibody was able to inhibit Prx I enzymatic activity using yeast thioredoxin reductase system.
  
  
  RESULTS
  IgG anti-Prx I antibody levels in SSc patients were significantly higher than healthy controls and this autoantibody was detected in 33% of SSc patients. The presence of IgG anti-Prx I antibody was associated with longer disease duration, more frequent presence of pulmonary fibrosis, heart involvement, and anti-topoisomerase I antibody and increased levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-Prx I antibody levels also correlated positively with renal vascular damage and negatively with pulmonary function tests. Furthermore, anti-Prx I antibody levels correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress. Immunoblotting analysis confirmed the presence of anti-Prx I antibody. Remarkably, Prx I enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-Prx I antibody.
  
  
  CONCLUSIONS
  These results suggest that elevated IgG anti-Prx I autoantibody is associated with the disease severity of SSc and that anti-PrxI antibody may enhance the oxidative stress by inhibiting Prx I enzymatic activity.
authors.affiliation: Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwata
authors.forename: F
authors.initials: F
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Komura
authors.forename: E
authors.initials: E
authors.lastname: Muroi
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: S
authors.initials: S
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology*; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000276:immunology*; D054464:Peroxiredoxins; D011673:Pulsatile Flow; D012595:Scleroderma, Systemic / Q000276:immunology*; D012720:Severity of Illness Index; D014797:Vital Capacity
chemical_list: D000975:Antioxidants; D001323:Autoantibodies; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D010544:Peroxidases; D054464:Peroxiredoxins