title: The significance of pretransplant donor-specific antibodies reactive with intact or denatured human leucocyte antigen in kidney transplantation.
abstract: Antibodies recognizing denatured human leucocyte antigen (HLA) can co-react with epitopes on intact HLA or recognize cryptic epitopes which are normally unaccessible to HLA antibodies. Their specificity cannot be distinguished by single antigen beads (SAB) alone, as they carry a mixture of intact and denatured HLA. In this study, we selected pretransplant sera containing donor-specific HLA class I antibodies (DSA) according to regular SAB analysis from 156 kidney transplant recipients. These sera were analysed using a SAB preparation (iBeads) which is largely devoid of denatured HLA class I, and SAB coated with denatured HLA class I antigens. A total of 241 class I DSA were found by regular SAB analysis, of which 152 (63%) were also found by iBeads, whereas 28 (11%) were caused by reactivity with denatured DNA. Patients with DSA defined either by regular SAB or iBeads showed a significantly lower graft survival rate (P = 0·007) compared to those without HLA class I DSA, whereas reactivity to exclusively denatured HLA was not associated with decreased graft survival. In addition, DSA defined by reactivity to class I SAB or class I iBeads occurred more frequently in female patients and in patients with historic HLA sensitization, whereas reactivity to denatured HLA class I was not associated with any of these parameters. Our data suggest that pretransplant donor-specific antibodies against denatured HLA are clinically irrelevant in patients already sensitized against intact HLA.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. h.g.otten@umcutrecht.nl
authors.forename: H G
authors.initials: HG
authors.lastname: Otten
authors.forename: M C
authors.initials: MC
authors.lastname: Verhaar
authors.forename: H P E
authors.initials: HP
authors.lastname: Borst
authors.forename: M
authors.initials: M
authors.lastname: van Eck
authors.forename: W G J
authors.initials: WG
authors.lastname: van Ginkel
authors.forename: R J
authors.initials: RJ
authors.lastname: Hené
authors.forename: A D
authors.initials: AD
authors.lastname: van Zuilen
mesh_terms: D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D011489:Protein Denaturation; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: denatured HLA; donor specific antibodies; kidney transplantation; single-antigen bead array