ORIGINAL ARTICLE Fucosylation of serum α 1 -acid glycoprotein in rheumatoid arthritis patients treated with infliximab Anna Olewicz-Gawlik & Izabela Korczowska-Łącka & Jan K. Łącki & Kamilla Klama & Paweł Hrycaj Received: 10 July 2006 / Revised: 1 January 2007 / Accepted: 24 January 2007 / Published online: 20 February 2007 # Clinical Rheumatology 2007 Abstract To analyze fucosylation of α 1 -acid glycoprotein (AGP) and to identify relations between AGP fucosylation and clinical and biochemical indices of disease activity in patients with rheumatoid arthritis (RA) treated with monoclonal antitumor necrosis factor (TNF) antibody infliximab, we examined 22 patients with RA who underwent a 54-week treatment with infliximab according to ATTRACT protocol. Blood samples were collected at baseline and before every infusion of infliximab. AGP fucosylation was measured using lectin-binding enzyme- linked immunosorbent assay utilizing fucose-specific lectin Aleuria aurantia (AAL). Moreover, the clinical status/ activity, erythrocyte sedimentation rate, serum C-reactive protein (CRP), antitrypsin, α 1 -antichymotrypsin, AGP reac- tivity with concanavalin A, serum C3 and C4 complement components, and serum concentrations of TNF and soluble TNF type 1 and type 2 receptors were determined. In most patients, the fucosylation of AGP decreased rapidly after first infusion of infliximab and remained low during the 54-week therapy (p <0.001). The decrease in AGP affinity to AAL closely followed changes in clinical and laboratory activity of RA and correlated with pretreatment concentrations of CRP (r =0.4986, p <0.05) and TNF (r =0.5181, p <0.05). The fucosylation of AGP can be a part of a negative feedback loop regulating migration of inflammatory cells and colla- genase-3 activity in RA. The decrease in AGP fucosylation accompanied by improvement in clinical and biochemical parameters of RA could possibly reflect reduced migration of inflammatory cells to inflamed joints and AGP-mediated inhibition of collagenase-3 as a response to infliximab treatment. Keywords α1-Acid glycoprotein . Rheumatoid arthritis . Selectins . Sialyl Lewis X Introduction α 1 -Acid glycoprotein (AGP) is an acute phase protein, which is known to increase several-fold in sera of patients with certain pathophysiological conditions including rheu- matoid arthritis (RA), malignant diseases, physical trauma, and bacterial infection. In contrast to C-reactive protein (CRP), which does not contain glycans, AGP is an extensively glycosylated molecule. The oligosaccharide component comprises approximately 45% of molecular weight of AGP and is essential for immunomodulatory effects of AGP [1]. It has been demonstrated that sialyl Lewis X (sLeX)-containing glycans are crucial for anti- neutrophil and anticomplement activity of AGP [2]; sLeX is the ligand for selectins, cell adhesion molecules involved in the recruitment of leukocytes from the circulation into a site of inflammation by mediating the process of tethering and rolling of leukocytes [3–5]. AGP-bound sLeX moieties inhibit cell adhesion to endothelium, as they compete with cellular selectin receptors. L-fucose is a necessary constituent of sLeX epitope. The fucosylation of AGP increases in certain pathological states [6–13] including RA [14–16]. As proinflammatory cyto- kines like tumor necrosis factor (TNF) are responsible for alterations in glycosylation of acute phase proteins [17, 18] TNF inhibition by infliximab may interfere with AGP synthesis and glycosylation in liver. This has already been Clin Rheumatol (2007) 26:1679–1684 DOI 10.1007/s10067-007-0572-7 A. Olewicz-Gawlik (*) : I. Korczowska-Łącka : J. K. Łącki : K. Klama : P. Hrycaj Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Przybyszewskiego 39, 60-356 Poznan, Poland e-mail: anolegaw@wp.pl