title: Do synovial fluid acute phase proteins from patients with rheumatoid arthritis originate from serum?
abstract: This study was performed in order to gain insight into the occurrence, glycosylation and the possible origin of the acute-phase proteins alpha1-acid glycoprotein (AGP) and alpha1-protease inhibitor (PI) in sera and synovial fluid from patients with rheumatoid arthritis (RA). Therefore paired sera and synovial fluid samples from patients with RA, and paired synovial fluid samples from right and left knees of patients with varying degrees of arthritis were studied. Crossed affinity immunoelectrophoresis (CAIE) was used with concanavalin A and Aleuria aurantia lectin for the detection of the degree of branching and fucosylation, respectively, and the monoclonal CSLEX-1 for the detection of Sialyl Lewis(X) (SLe(X)) groups on AGP. For PI, not only CAIE, but also high-pressure-anion-exchange chromatography with pulsed amperometric detection was used to study the glycosylation. It was established that the concentrations of AGP and PI were increased in the serum of RA patients compared to normal healthy controls, but that the concentration of both proteins, as well as albumin, was significantly lower in synovial fluid than in serum. Furthermore, the type of glycosylation of both AGP and PI found in RA was significantly different from that found in normals, with increased fucosylation, but there were no major differences in the degree of branching of AGP- or PI-glycans in RA, compared to normals. No differences in glycosylation could be established between serum and synovial fluid in RA. For PI an increased fucosylation was found, both in serum and synovial fluid, using both methods of detection, and it could be established that only the alpha1-->3- and not the alpha1-->6-fucosylation of PI was affected by RA. The increased fucosylation of AGP resulted in an increased expression of SLe(X) on AGP-glycans. Since the alpha1-->3-fucosylation of AGP was significantly increased in both serum and synovial fluid from RA patients, and this correlated with systemic but not with local disease parameters, it can be suggested that acute phase proteins in synovial fluid are most probably of hepatic origin.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: E C
authors.initials: EC
authors.lastname: Havenaar
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolhain
authors.forename: G A
authors.initials: GA
authors.lastname: Turner
authors.forename: M T
authors.initials: MT
authors.lastname: Goodarzi
authors.forename: E C
authors.initials: EC
authors.lastname: van Ommen
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: W
authors.initials: W
authors.lastname: van Dijk
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000378:metabolism; D009961:Orosomucoid / Q000276:immunology / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D013582:Synovial Fluid / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D009844:Oligosaccharides; D009961:Orosomucoid; D000080506:Sialyl Lewis X Antigen; D000515:alpha 1-Antitrypsin