title: Emerging role of donor-specific anti-human leukocyte antigen antibody determination for clinical management after solid organ transplantation.
abstract: Preformed and de novo donor-specific HLA antibodies (DSA) have been associated with allograft dysfunction and failure. The application of solid-phase methods have increased the sensitivity and specificity of antibody detection; however the clinical significance of these DSA is under evaluation. In the present study, we summarize six cases (four renal transplant recipients, one multivisceral recipient, and one heart-and-lung transplant recipient) to illustrate the role of the histocompatibility laboratory in providing the most comprehensive workup to assess the risk of graft dysfunction associated with antibody-mediated rejection (AMR). These cases illustrate the potential risk assessment for AMR in various situations: (1) in patients exhibiting low levels of DSA pretransplantation; (2) protocol immunosuppression minimization during stepwise weaning; and (3) desensitization protocols. Furthermore, increased sensitivity of DSA determination is indicated for the interpretation of focal C4d and its clinical significance. The clinical relevance of monitoring for circulating DSA with solid-phase single-antigen assays is also discussed. These cases exemplify the rationale for all patients to be monitored for DSA post-transplantation, with the frequency adjusted based on the individual risk for AMR.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. zeevia@upmc.edu
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: John G
authors.initials: JG
authors.lastname: Lunz
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Steven
authors.initials: S
authors.lastname: Webber
authors.forename: Alin
authors.initials: A
authors.lastname: Girnita
mesh_terms: D003181:Complement C4 / Q000276:immunology / Q000378:metabolism; D003888:Desensitization, Immunologic; D006084:Graft Rejection; D006680:HLA Antigens / Q000276:immunology*; D016041:Heart-Lung Transplantation; D006648:Histocompatibility; D006801:Humans; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation; D008991:Monitoring, Physiologic; D016377:Organ Transplantation; D011182:Postoperative Care; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*
chemical_list: D003181:Complement C4; D006680:HLA Antigens; D007518:Isoantibodies