title: Vimentin antibody production in transplant patients and immunomodulatory effects of vimentin in-vitro.
abstract: We investigated the presence of antibodies to vimentin in 150 patients awaiting transplant, (50 kidney, 50 liver and 50 thoracic) and in 51 previously transplanted kidney patients whose grafts had failed. Patients with primary end stage thoracic or kidney disease did not have increased levels of vimentin antibodies, but those with primary liver failure and those with kidney graft failure did. Those with kidney graft failure were more likely to form vimentin antibodies if the patient was HLA-DQ2 positive (p=<0.001). Further to this, we observed antibody mediated rejection in five HLA-DQ2 positive re-transplant patients where no other antibodies were identified. We investigated the effects of vimentin protein on cytokine production in phytohaemagglutinin stimulated and unstimulated peripheral blood mononuclear cells. When exposed to vimentin at low levels there was increased production of IL-10. When cultures were stimulated, there was a decrease in IL-10, IL-2 and IFN-gamma production and a large increase in IL-4 production (p=0.028) compared to the controls. These results suggest that under normal conditions exposure to vimentin can lead to regulation of the immune response. However, if the immune system is active, exposure to vimentin can enhance Th-2 immunity.
authors.affiliation: National Health Service, Blood and Transplant, Newcastle, Newcastle Upon Tyne NE2 4NQ, United Kingdom. Electronic address: vaughan.carter@nhsbt.nhs.uk.
authors.forename: Vaughan
authors.initials: V
authors.lastname: Carter
authors.forename: W Martin
authors.initials: WM
authors.lastname: Howell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D056747:Immunomodulation; D007223:Infant; D007676:Kidney Failure, Chronic / Q000276:immunology*; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D017093:Liver Failure / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000276:immunology*; D012086:Reoperation; D014746:Vimentin / Q000276:immunology* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000906:Antibodies; D016207:Cytokines; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D014746:Vimentin
keywords: APCs; HLA; IL; Ig; MHC class I related chain; MIC; PBMCs; PHA; T helper T cell; Th; antigen presenting cells; human leukocyte antigen; immunoglobulin; interleukin; peripheral blood mononuclear cells; phytohaemagglutinin