title: Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: a 30-month analysis in living donor kidney transplantation.
abstract: Selection of donors for kidney transplantation depends on accurate prediction of risk factors for immunologic rejection. Historically, cytotoxicity crossmatch (CXM) examining lysis of donor cells by preformed anti-human leukocyte antigen (HLA) antibodies (Abs) has been considered the best predictor of immunologic rejection. However, there is much interest in defining anti-HLA Ab specificity in recipient sera by immunoassay to predict crossmatch results and aid in donor selection. Current immunoassays for anti-HLA Abs are highly sensitive, though correlation between Abs detected by immunoassay and their functional relevance in CXM and subsequent transplantation is not well defined. In this study, we retrospectively examined the predictive value of detection of donor-specific anti-HLA Abs (DSA) by Luminex Single Antigen assay from 149 consecutive living donor kidney transplant recipients. We demonstrate that detection of DSA by immunoassay accurately predicted negative crossmatch and graft survival. However, this approach had limited sensitivity for predicting positive crossmatch, attributable to either limited typing of donor HLA-DQ and -DP alleles or due to non-HLA Abs. False-positive prediction of CXM correlated with detection of "weak" Abs with low mean fluorescence intensity (MFI < 2000). Furthermore, we found that a ratio of the MFI of the DSA bead to the MFI of the positive control bead was a better method for identifying weak DSA that did not result in CXM-positive reactions. Interestingly, patients with weak DSA and negative CXM had equivalent graft survival over an 18 month follow-up period, suggesting that weak DSA may not preclude transplantation.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Morris
authors.forename: Donna L
authors.initials: DL
authors.lastname: Phelan
authors.forename: Martin D
authors.initials: MD
authors.lastname: Jendrisak
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D046148:Donor Selection / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation; D019520:Living Donors; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D006680:HLA Antigens