Routine Solid Phase Multiplex Anti-HLA Antibody Tests Predict Platelet Refractoriness.

OBJECTIVES: No validated screening methods identify patients at risk for human leukocyte antigen (HLA) alloimmune-mediated platelet refractoriness (alloPR). We determined if bead-based HLA antibody tests could predict risk of developing HLA alloPR. METHODS: Hematopoietic progenitor cell transplant patients screened for HLA antibodies without prior refractoriness were identified. Phenotype bead screening results were compared between patients who later did and did not develop alloPR. RESULTS: Seven of 27 patients identified subsequently developed alloPR. The panel reactive antibody (PRA) and mean fluorescence intensity (MFI) of the 10 most reactive beads in the initial screen were significantly higher among patients who later developed alloPR (P < .001). Specifically, PRA of more than 30% and mean MFI of 1,500 or more in the most reactive beads identified at-risk patients. Administration of HLA-compatible platelets yielded significant posttransfusion count increments compared with routine platelets. CONCLUSIONS: HLA antibody screening by phenotype bead assay may prospectively identify at-risk patients for the development of alloPR. However, clinical trials are needed to validate these findings.

HLA-DQ Mismatching and Kidney Transplant Outcomes.

BACKGROUND AND OBJECTIVES: Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection. RESULTS: A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P<0.01), but not in deceased kidney donor recipients (HR, 1.05; 95% CI, 0.98 to 1.12; P=0.18) (P value for interaction <0.01). When taking cold ischemic time into account, HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P=0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P=0.49) (P value for interaction <0.01). Recipients with one or two HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P<0.01) in deceased donor and 1.14 (95% CI, 1.03 to 1.27; P=0.02) in living donor kidney transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not. CONCLUSIONS: HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants.

Anti-HLA antibody testing in hematology patients.

Anti-human leukocyte antigens (HLA) antibodies can adversely impact the care of hematology patients. In particular, HLA antibody testing provides important information for optimal stem cell and platelet donor selection in the management of stem cell recipients and platelet refractory patients. Current testing methods for HLA antibodies are briefly reviewed, with particular emphasis on laboratory and clinical issues associated with solid-phase multiplex assays.

Anti-HLA alloantibodies in surgical patients refractory to platelet transfusion.

Alloimmune platelet refractoriness (alloPR) among actively bleeding surgical patients with thrombocytopenia represents a life-threatening problem. Here we present three cases in which surgical bleeding was complicated by life-threatening thrombocytopenia and alloPR. We demonstrate that the human leukocyte antigens (HLA) antibodies associated with alloPR are broadly reactive and in high concentration, are not removed by hemodilution, and are not absorbed by transfusion of multiple doses of platelet concentrates. HLA alloPR may be under-recognized among surgical patients. Research is needed to develop pre-operative screening methods that will identify patients in need of specialized platelet support using HLA compatible donor products.