title: Identification of Non-HLA antigens targeted by alloreactive antibodies in patients undergoing chronic hemodialysis.
abstract: The only treatment of end-stage renal disease patients undergoing chronic dialysis is kidney transplantation. However, about half of graft recipients encounter organ loss within ten years after renal transplantation. There is emerging evidence that the presence of alloreactive antibodies against non-HLA antigens in the serum of the recipient prior transplantation is associated with higher incidence of chronic rejection. However, the molecular identity of these antigens is largely unknown. To determine the most common non-HLA antigens, we tested lymphocytic extracts from 20 healthy volunteers with sera of 28 patients on the transplantation waiting list by Western blotting. There was a group of five proteins that was recognized by most sera. Using patient's own lymphocytes revealed that autoimmunity plays a minor role in this recognition. Two-dimensional Western blotting experiments followed by mass spectrometry identified the antigens as tubulin beta chain, vimentin, lamin-B1, and Rho GDP-dissociation inhibitor 2. A detailed analysis of vimentin expression revealed that the antigenic 60 kDa isoform is underrepresented in patient's lymphocytes in comparison to those of healthy volunteers. The study revealed that preformed alloreactive antibodies are directed against a small number of specific protein isoforms. Our findings could provide a basis for future improvement of donor-recipient matching.
authors.affiliation: Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Senada
authors.initials: S
authors.lastname: Bilalic
authors.forename: Michael
authors.initials: M
authors.lastname: Veitinger
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Ahrer
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gruber
authors.forename: Maria
authors.initials: M
authors.lastname: Zellner
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
authors.forename: Gregor
authors.initials: G
authors.lastname: Bartel
authors.forename: Daniel
authors.initials: D
authors.lastname: Cejka
authors.forename: Christian
authors.initials: C
authors.lastname: Reichel
authors.forename: Veronika
authors.initials: V
authors.lastname: Jordan
authors.forename: Christopher
authors.initials: C
authors.lastname: Burghuber
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Mühlbacher
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: Rudolf
authors.initials: R
authors.lastname: Oehler
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D006435:Renal Dialysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies