To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc).
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.
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.
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.
"The positive correlation between serum BDNF levels and forced vital capacity could also reflect the potential link between this NT and oxidative stress. Forced vital capacity is known to decrease with enhanced oxidative stress in SSc , . Furthermore, BDNF-induced activation of TrkB signaling in vivo promotes prostacyclin biosynthesis by cerebral arteries . "
[Show abstract][Hide abstract] ABSTRACT: Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data.
Serum samples were obtained from 55 SSc patients and 32 control subjects to measure NTs levels by ELISA and to determine their relationships with SSc profiles.
Serum NGF levels were higher in SSc patients (288.26 ± 170.34 pg/mL) than in control subjects (170.34 ± 50.8 pg/mL, p<0.001) and correlated with gammaglobulins levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls (1121.9 ± 158.1 vs 1372.9 ± 190.9 pg/mL, p<0.0001), especially in pulmonary arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05). NT-3 levels were similar in SSc and in the control group (2657.2 ± 2296 vs 2959.3 ± 2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF levels in the SSc group (and not in controls).
Low BDNF serum levels were not previously documented in SSc, particularly in the diffuse SSc subset and in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative correlation between NGF and BDNF levels observed in SSc and not in healthy controls could be implicated in sympathic vascular dysfunction in SSc.
PLoS ONE 11/2010; 5(11):e13918. DOI:10.1371/journal.pone.0013918 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This is a review of autoantibodies described in systemic sclerosis with an emphasis on recently published studies. In the past, most, if not all of the discussion on this topic focused on antinuclear antibodies, but it is now appreciated that autoantibodies to cytoplasmic, cell surface, intercellular and plasma components are also important in the context of systemic sclerosis.
A number of recent studies have highlighted the disease associations of autoantibodies and the potential pathogenic role of the more traditional autoantibodies, such as antitopoisomerase I and anticentromere antibodies. The recent identification of autoantibodies directed to the platelet-derived growth factor receptor is of particular interest because of its possible association with the pathogenesis of systemic sclerosis.
Autoantibodies in systemic sclerosis are associated with demographic, diagnostic, pathological, and prognostic features of the disease. Emerging research on the pathogenic roles of newer autoantibodies provides valuable insights into disease pathogenesis and potential therapeutic targets.
Current Opinion in Rheumatology 12/2007; 19(6):580-91. DOI:10.1097/BOR.0b013e3282e7d8f9 · 4.89 Impact Factor
Woting Gan, Yanqi Dang, Xin Han, Shuang Ling, Ju Duan, Jun Liu, Jin-Wen Xu
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