Anti-SELE monoclonal antibody, clone CL2/6

Objective. To investigate aggrecan degradation in juvenile idiopathic arthritis (JIA). Methods. The pattern and abundance of aggrecan fragments in synovial fluid (SF) aspirates from JIA patients were analyzed and compared with aggrecan fragments in SF from patients with other arthritides, children with knee injury, and a knee-healthy reference group. Concentrations of sulfated glycosaminoglycan (sGAG) in SF were measured by Alcian blue precipitation assay. Aggrecan fragments were purified by dissociative CsCl density-gradient centrifugation, deglycosylated, and analyzed by Western blot using antibodies specific for either aggrecanase-derived ARGS, SELE, and KEEE neoepitopes or the aggrecan G3 domain. Results. The concentration of sGAG in SF from patients with JIA was significantly lower compared with that in SF from patients with osteoarthritis (OA) (P < 0.001), patients with juvenile knee injury (P = 0.006), and knee-healthy controls (P = 0.022). Western blot analysis revealed KEEE, SELE, and G3 fragments generated by aggrecanase cleavage in the chondroitin sulfate-rich region of aggrecan in patients with JIA. The pattern of aggrecan fragments in JIA patients was not identical to that in pooled OA SF, although there were notable similarities. Surprisingly, aggrecanase-derived ARGS fragments were barely detectable in JIA SF, in marked contrast to levels in OA SF. Conclusion. Aggrecanases appear to cleave minimally in the interglobular domain of aggrecan in JIA patients despite robust levels of cleavage in the chondroitin sulfate-rich region. These results suggest that in JIA, unlike other arthritides, aggrecanase cleavage in the aggrecan interglobular domain might not be a major pathogenic event.

Background and Aims. A common single nucleotide polymorphism in the E-selectin (SELE) gene S149R results in the loss of E-selectin ligand binding specificity. The 149R allele has been associated with severe cardiovascular diseases. We hypothesized that S149R may regulate platelet activation after stimuli associated with perioperative procedures in patients undergoing isolated coronary artery bypass grafting (CABG). Associations between the S149R polymorphism and an increased risk of perioperative acute thrombotic events with regards to a platelet count and activity were analyzed. Methods. In elective CABG patients (n = 152) we analyzed associations between S149R polymorphism and an increased risk of perioperative acute thrombotic events with regard to platelet count and activity. The S149R SELE gene polymorphism was determined by real-time polymerase chain reaction. Platelet count and activation marker (beta-thromboglobulin-beta TG) were evaluated. Results. Prevalence of the S149R genotypes was as follows: 81.8% (n = 121) of homozygotes (149SS), 15.5% (n = 23) of heterozygotes and 2.7% (n = 4) of homozygotes (149RR). The 149R allele carriers had significantly higher postoperative beta TG levels than the homozygotes (97 [79-120] vs. 76 [66-91] IU/mL, p = 0.03). Sixteen patients had adverse events: myocardial infarction (n = 14), stroke (n = 1) and fatal pulmonary embolism (n = 1). Twelve patients were carriers of the 149R allele. Relative risk (RR) of postoperative adverse events in the 149R allele carriers was 2.03 with 95% CI (1.05-3.03). Conclusions. Postoperative platelet activation is related to the S149R polymorphism, which enhances the risk of adverse events after CABG. (C) 2011 IMSS. Published by Elsevier Inc.