Rheumatology Advance Access published online on August 7, 2007
Rheumatology, doi:10.1093/rheumatology/kem181
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Antibodies against the VRT101 laminin epitope correlate with human SLE disease activity and can be removed by extracorporeal immunoadsorption
Department of Medicine ‘D’, Meir Medical Center, Tel-Aviv University, Kfar-Saba, 1Department of Medicine, Hadassah University Hospital, 2The Authority for Animal Facilities, Hebrew University, Jerusalem and 3Division of Clinical Immunology and Allergy, Bnai-Zion Medical Center, Haifa, Israel.
Correspondence to:
H. Amital, MD MHA, Head of Department of Medicine ‘D’, Meir Medical Center, Tshernichovsky 59, Kfar-Saba, 44281, Israel. E-mail: howard.amital{at}clalit.org.il, hamital{at}netvision.net.il
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Abstract |
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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-
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.
KEY WORDS: SLE, Lupus nephritis, Laminin, Anti-DNA antibodies, Autoantibodies
*Y.N. is the incumbent of the Leifermann chair in Osteoporosis and Arthritis of the Hebrew University.
Submitted 21 March 2007;
revised version accepted 7 June 2007.
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