dimethylarginine and Scleroderma--Systemic

The purpose of this study is to clarify the relationship between systemic sclerosis (SSC) and oxidative stress markers in blood.. We conducted a systematic literature search of databases, including PubMed and Embase, for studies reporting circulating oxidative stress markers in patients with SSC and controls published from 1980 to December 2015. Standardized mean differences (SMDs) and 95% confidence intervals (95%CI) were calculated.. Of the 1076 articles initially retrieved, 47 were included in our meta-analysis including 12 oxidative stress markers. The concentrations of nitric oxide (SMD = 0.77; 95%CI: 0.18, 1.36; p = 0.01), malondialdehyde (SMD =1.63; 95%CI: 1.03, 2.24; p = 0.000), asymmetric dimethylarginine (SMD = 0.51; 95%CI: 0.12, 0.91; p = 0.011), and ROOH (SMD = 3.37; 95%CI: 0.28, 6.46; p = 0.033) in the blood of patients with SSC were higher than those of the control group, whereas the concentrations of superoxide dismutase (SMD = -1.11; 95%CI: -1.57, -0.65; p = 0.000) and vitamin C (SMD = -1.12; 95%CI: -1.51, -0.73; p = 0.000) were lower than in the control group.. The oxidative stress markers in blood for patients with SSC were aberrant, indicating the imbalanced states of oxidation and antioxidation in SSC.

Topics: Arginine; Ascorbic Acid; Biomarkers; Case-Control Studies; Humans; Malondialdehyde; Nitric Oxide; Oxidative Stress; Scleroderma, Systemic; Superoxide Dismutase

SSc is a CTD characterized by vascular involvement, with generalized disturbance of the microcirculation, which may lead to pulmonary artery hypertension (PAH). Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor. Increased concentrations of plasma ADMA may also contribute to endothelial dysfunction in patients with pulmonary vascular disease. The aim of our study was to elucidate the possible relationship between serum ADMA and PAH in patients with SSc. Moreover, we sought to investigate the effect of ADMA levels on the functional capacity of these patients.. Plasma ADMA levels were measured in 66 patients with SSc (63 females, mean age 57.8 +/- 12.8 yrs, median duration of disease 9.9 yrs, 47 with lcSSc and 19 with dcSSc disease) and 30 healthy controls (29 females, mean age 58.2 +/- 8.4 yrs). Systolic pulmonary artery pressure (sPAP) assessed by echocardiography, lung function tests, 6-min walk test (6MWT) and serum ADMA levels were recorded from patients.. In 24 patients, the diagnosis of PAH was established. Mean value of ADMA for SScPAH patients was 0.44 +/- 0.22 micromol/l compared with 0.26 +/- 0.18 micromol/l for patients without PAH and 0.25 +/- 0.20 micromol/l for controls (P = 0.001). ADMA levels were inversely correlated with the 6MWT (r = -0.55, P = 0.005).. In patients with SScPAH, increased ADMA serum levels and their negative association with exercise capacity suggests that the NO pathway is involved in the development of pulmonary vascular disease.

Topics: Aged; Analysis of Variance; Arginine; Case-Control Studies; Echocardiography; Echocardiography, Doppler; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Respiratory Function Tests; Scleroderma, Systemic

Anti-Sm antibodies, identified in 1966 by Tan and Kunkel, are highly specific serological markers for systemic lupus erythrematosus (SLE). Anti-Sm reactivity is found in 5-30% of SLE patients, depending on the autoantibody detection system and the racial background of the SLE population. The Sm autoantigen complex comprises at least nine different polypeptides. All of these core proteins can serve as targets of the anti-Sm B-cell response, but most frequently the B and D polypeptides are involved. Because the BB'Sm proteins share cross-reactive epitopes (PPPGMRPP) with U1 specific ribonucleoproteins, which are more frequently targeted by antibodies that are present in patients with mixed connective tissue disease, the SmD polypeptides are regarded as the Sm autoantigens that are most specific to SLE. It was recently shown that the polypeptides D1, D3 and BB' contain symmetrical dimethylarginine, which is a component of a major autoepitope within the carboxyl-terminus of SmD1. In one of those studies, a synthetic dimethylated peptide of SmD1 (amino acids 95-119) exhibited significantly increased immunoreactivity as compared with unmodified SmD1 peptide. Using immobilized peptides, we confirmed that the dimethylated arginine residues play an essential role in the formation of major SmD1 and SmD3 autoepitopes. Moreover, we demonstrated that one particular peptide of SmD3 represents a more sensitive and more reliable substrate for the detection of a subclass of anti-Sm antibodies. Twenty-eight out of 176 (15.9%) SLE patients but only one out of 449 (0.2%) control individuals tested positive for the anti-SmD3 peptide (SMP) antibodies in a new ELISA system. These data indicate that anti-SMP antibodies are exclusively present in sera from SLE patients. Thus, anti-SMP detection using ELISA represents a new serological marker with which to diagnose and discriminate between systemic autoimmune disorders.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antinuclear; Antibody Specificity; Antigen-Antibody Reactions; Arginine; Arthritis, Rheumatoid; Autoantigens; Autoimmune Diseases; Cross Reactions; Dermatomyositis; DNA; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes; Epstein-Barr Virus Nuclear Antigens; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Mixed Connective Tissue Disease; Polymyositis; Reference Standards; Ribonucleoproteins, Small Nuclear; Scleroderma, Systemic; Sensitivity and Specificity; Sjogren's Syndrome; snRNP Core Proteins