Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging surface plasmon resonance

Introduction  

Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology.     

Swainsonine inhibits macrophage receptor-mediated uptake and degradation of a mannosyl-oligosaccharide

Rat pulmonary macrophages were incubated in the presence of a radiolabeled mannosyl-oligosaccharide obtained from ovalbumin. Receptor-mediated endocytosis and degradation of this ligand by the cells was followed in the presence or absence of swainsonine, an inhibitor of alpha-mannosidases. The results indicated that at higher concentrations (greater than 1 microgram/ml) of swainsonine, both the internalization and degradation of the radiolabeled ligand were inhibited. At a concentration of 0.1 microgram/ml of swainsonine, only the degradation was inhibited while the uptake was unaltered. The degradation of the oligosaccharide was blocked due to the inhibition of lysosomal alpha-mannosidase. However, the inhibition of lysosomal alpha-mannosidase was reversible upon withdrawal of swainsonine.     

Partial characteristics of an analog of pyridinoline isolated from human skin

The most abundant amine in acid hydrolysates of human skin, eluting in the crosslink region of a reversed-phase HPLC chromatogram, has the same retention time as pyridinoline standard. This amine is not pyridinoline, since it is a weak fluorophore and its U/V spectrum does not agree with that of pyridinoline. The unknown amine was isolated and characterized by fast atom bombardment mass spectrometry and its structure is consistent with a deoxy-analogue of pyridinoline. It may be a crosslink component of some biological importance, since it is not detectable in skin from a patient with Marfan's Syndrome.