OBJECTIVE: We have previously shown that murine pathogenic lupus autoantibodies bind to VRT101, a 21-mer peptide located at the globular part of the laminin-alpha chain. In this study, we evaluated whether VRT101 also serves as a target for human lupus antibodies, upholding the hypothesis that VRT101 may serve as a potential target in the therapy of lupus. METHODS: Anti-VRT101 and anti-dsDNA reactivity were measured in the serum of lupus patients and compared with that of healthy individuals and patients with other rheumatic disorders. Statistical correlations between disease activity measured by the SLEDAI-2k scale and compatible serum anti-VRT101 and anti-dsDNA levels were defined. A VRT101-coupled sepharose column was assessed for its efficacy in removing serum anti-VRT101 antibody and its safety in extracorporeal apheresis in sheep. RESULTS: Anti-VRT101 and anti-dsDNA antibodies were significantly higher in SLE patients compared with patients with other rheumatic conditions. A high degree of correlation was detected between anti-VRT101 levels and the SLEDAI-2k activity in patients with SLE. Immunoadsorption of lupus patients' sera on the VRT101-sepharose column removed most of the anti-VRT101 antibodies. The column was found to transfer effectively 3l of normal sheep plasma without significant removal of non-specific antibodies or other proteins. CONCLUSIONS: Anti-VRT101 anibodies are abundantly detected in the serum of patients with SLE and correlate with disease activity. Specific removal of serum anti-VRT101 by extracorporeal plasmapheresis with specific immunoadsorption on the VRT101-coupled sepharose columns may serve as a new therapeutic tool for specific immunoadsorption of pathogenic antibodies in SLE patients.
OBJECTIVE: We have previously shown that murine pathogenic lupus autoantibodies bind to VRT101, a 21-mer peptide located at the globular part of the laminin-alpha chain. In this study, we evaluated whether VRT101 also serves as a target for human lupus antibodies, upholding the hypothesis that VRT101 may serve as a potential target in the therapy of lupus. METHODS: Anti-VRT101 and anti-dsDNA reactivity were measured in the serum of lupus patients and compared with that of healthy individuals and patients with other rheumatic disorders. Statistical correlations between disease activity measured by the SLEDAI-2k scale and compatible serum anti-VRT101 and anti-dsDNA levels were defined. A VRT101-coupled sepharose column was assessed for its efficacy in removing serum anti-VRT101 antibody and its safety in extracorporeal apheresis in sheep. RESULTS: Anti-VRT101 and anti-dsDNA antibodies were significantly higher in SLEpatients compared with patients with other rheumatic conditions. A high degree of correlation was detected between anti-VRT101 levels and the SLEDAI-2k activity in patients with SLE. Immunoadsorption of lupus patients' sera on the VRT101-sepharose column removed most of the anti-VRT101 antibodies. The column was found to transfer effectively 3l of normal sheep plasma without significant removal of non-specific antibodies or other proteins. CONCLUSIONS: Anti-VRT101 anibodies are abundantly detected in the serum of patients with SLE and correlate with disease activity. Specific removal of serum anti-VRT101 by extracorporeal plasmapheresis with specific immunoadsorption on the VRT101-coupled sepharose columns may serve as a new therapeutic tool for specific immunoadsorption of pathogenic antibodies in SLEpatients.
Authors: Amy G Clark; Qihua Fan; Graham F Brady; Katherine M Mackin; Evan D Coffman; Melissa L Weston; Mary H Foster Journal: Autoimmunity Date: 2013-01-09 Impact factor: 2.815