The significance of pretransplant donor‐specific antibodies reactive with intact or denatured human leucocyte antigen in kidney transplantation

Summary 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 (i B eads) 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 i B eads, whereas 28 (11%) were caused by reactivity with denatured DNA . Patients with DSA defined either by regular SAB or i B eads 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 i B eads 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 .