i(3)so3-galactosylceramide and Arthritis--Rheumatoid

Rheumatoid arthritis (RA) patients have accelerated atherosclerosis (AS) leading to excess cardiovascular morbidity and mortality, but traditional risk factors for cardiovascular disease (CVD) are invalid to explain the problem. Sulfatides, as major components of serum lipoproteins, are synthesized in the liver. These molecules are reported to play an important role in the development of AS, thrombogenesis, and inflammation. However, it is unclear whether sulfatides are responsible for such issue. To elucidate the possible association between serum sulfatide and the accelerated progress of AS, evaluated by carotid intima-media thickness (CIMT), and ascertain the related mechanism underlying the correlation in RA cases.. We performed an observational study of 144 patients with RA and 120 sex and age-matched controls. Meanwhile, 107 patients (of the 144 RA patients enrolled at baseline) were invited to undergo a second measurement after 12 months. Serum sulfatide levels of all the enrolled subjects were quantified by mass spectrometry after they were converted into lysosulfatides (LS), and then calculated as the sum of the levels of seven LS molecular species. Serum oxidative stress marker, malondialdehyde (MDA) was detected by ELISA. We subsequently statistically analyzed the causalities between carotid AS and clinical parameters, and the association of serum sulfatide with other variables. Multivariable logistic regression analysis was finally employed by taking all factors to identify independent determinant for carotid atherosclerotic plaque and serum sulfatide level.. A gradual declined trend in serum sulfatide levels was observed in control subjects, non-plaque group, and the plaque group (8.56 ± 1.37 nmol/mL, 5.63 ± 1.57 nmol/mL, 3.18 ± 1.32 nmol/mL, respectively, p < 0.01), along with an increased value of CIMT (0.63 ± 0.07 mm, 0.92 ± 0.14 mm, 1.43 ± 0.22 mm, respectively, p < 0.01). Meanwhile, a negative linear correlation between CIMT and serum sulfatide was further confirmed by Spearman's analysis (r = -0.622, p < 0.01). Eventually, multivariate logistic regression analysis identified serum MDA as the only independent factor for the abnormal level of serum sulfatide, and serum sulfatide was detected as a significant protective factor for the occurrence of carotid plaques in RA cases (p < 0.01), which was confirmed repeatedly by our cross-sectional and longitudinal studies.. Excessive abnormal levels of oxidative stress decreased serum sulfatide levels, followed by a high occurrence of AS in RA patients. Serum sulfatide level might be useful as a predictor (biomarker) for the progression of AS in RA cases.

Topics: Arthritis, Rheumatoid; Biomarkers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Humans; Plaque, Atherosclerotic; Risk Factors; Sulfoglycosphingolipids

Gangliosides are a diverse class of glycolipids found in the plasma membrane of mammalian cells and are particularly abundant in cells of the nervous system. Serum antibodies to gangliosides have been detected in various neurological disorders with some evidence that they play a pathogenic role. In this study, we have investigated whether anti-ganglioside antibodies were elevated in a group of patients with rheumatoid arthritis (RA) who developed peripheral neuropathy (PN). An ELISA technique was used to test sera from 28 patients with RA and PN. 38 RA patients without PN and 20 normal controls for the presence of IgG and IgM anti-GM1 and sulphatide antibodies. The patients with RA and PN had higher pain scores (P < 0.005), more extra-articular features (P < 0.05), higher erosive scores (P < 0.0001), lower haemoglobin (P < 0.005), higher ESR (P < 0.001) and were more often on disease-modifying drugs (P < 0.05). Twelve RA patients with PN (43%), but only two RA controls (5%), had positive titres against one or more gangliosides (P < 0.001). The neurologic disability score (NDS) correlated with RA duration (P < 0.05), and with levels of IgM anti-GM1 (P < 0.001) and IgM anti-sulphatide (P < 0.05) antibodies. We conclude that PN is more common in patients with severe rheumatoid disease, and a significant proportion have elevated levels of anti-ganglioside antibodies.

Topics: Aged; Antibodies; Arthritis, Rheumatoid; Female; G(M1) Ganglioside; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Peripheral Nervous System Diseases; Severity of Illness Index; Sulfoglycosphingolipids