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VIMENTIN ANTIBODIES: A POTENTIAL ROLE IN EARLY GRAFT DAMAGE AND LATE GRAFT FAILURE IN RENAL ALLOGRAFTS?.
Vaughan Carter FIBMS 1, Brian K. Shenton PhD 2, Brian Susskind PhD 3, Marlene L. Rose PhD 4 and W. Martin Howell PhD 1. 1 Histocompatibility and Immunogenetics, National Blood Service, Newcastle upon Tyne, Tyne and Wear, United Kingdom ; 2 Dept of Surgery, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom ; 3 Transplantation Immunology, Hoxworth Blood Centre, Cincinnati, OH, USA and 4 Transplant Immunology, Imperial College, Harefield, Middlesex, United Kingdom .
Vimentin is ubiquitous in cells of mesenchymal origin and may be exposed during transplant rejection. Vimentin antibodies have been demonstrated in autoimmune disease and are found de-novo following cardiac and more recently renal transplantation.
95 patients listed for primary renal transplant and 45 patients suffering chronic allograft loss were tested for vimentin antibodies using a novel in-house flow cytometric assay. Results were compared with a reference control group of healthy blood donors. A significant difference between the patient groups was found (high anti-vimentin in 19/45 chronic rejection and 19/95 pre-transplant; p=0.008). In chronic graft loss an association between HLA-DQ2 and development of vimentin antibodies was found: HLA-DQ2 positive relative mean fluorescence (RMF) range 0.58-5.22, mean 2.14. HLA-DQ2 negative RMF range 0.3-2.98, mean 1.05 (p=0.001).
In addition 3 patients undergoing secondary renal transplant who were HLA-DQ2 positive, ABO matched, HLA antibody and crossmatch negative had early vascular damage in the presence of raised and increasing levels of vimentin antibodies.
Peptide modelling has identified a vimentin peptide complementary to the 5 peptide binding anchor residues of the DQA1*0501/DQB1*0201 encoded molecule. Presentation of this peptide could lead to T-cell-dependent production of vimentin antibodies observed in these patients.