title: Pretransplant donor-specific anti-HLA antibodies as predictors of early allograft rejection in ABO-compatible liver transplantation.
abstract: The significance of preexisting donor-specific HLA antibodies (HLA-DSAs) for liver allograft function is unclear. Our previous studies have shown that humoral alloreactivity frequently accompanies acute cellular rejection (ACR). In the present study, we set out to determine whether pretransplant HLA-DSAs correlate with clinically significant ACR in the first 90 days after transplantation and, if so, to determine their predictive values. Class I HLA-DSAs and class II HLA-DSAs were determined by single-antigen bead flow cytometry for 113 consecutive adult transplants. A statistical analysis was performed for data from 109 consecutive patients with graft survival greater than or equal to 90 days. All patients who developed biochemical graft dysfunction underwent liver biopsy for hematoxylin-eosin and complement component 4d staining. Cox proportional hazards models and associated hazard ratios revealed a significant association of pretransplant HLA-DSAs with clinically significant ACR: this association started with a mean fluorescence intensity (MFI) as low as 300 for both class I (hazard ratio = 2.7, P  < 0.01) and class II (hazard ratio = 6.0, P  < 0.01). Pretransplant HLA-DSAs were associated with an increased risk of ACR: P  < 0.01 for class I (42% versus 18%), P  < 0.001 for class II (37% versus 7%), and P  < 0.001 for either class I or II (36% versus 3%). Class I or II HLA-DSAs with an MFI ≥ 1000 had the best positive predictive value for clinically significant ACR at 46%, whereas class I or II HLA-DSAs with an MFI ≥ 300 had the best negative predictive value at 97.1%. Although our study was based on consecutive patients, it was limited by the relatively low number of single-center subjects. In conclusion, the present study indicates that pretransplant HLA-DSAs, even at low levels of allosensitization, correlate with the risk of clinically significant ACR. Our findings suggest that anti-human leukocyte antigen antibodies could serve as donor-specific markers of immunoreactivity to the liver graft.
authors.affiliation: Departments of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Alexandru I
authors.initials: AI
authors.lastname: Musat
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Pigott
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ellis
authors.forename: Rashmi M
authors.initials: RM
authors.lastname: Agni
authors.forename: Glen E
authors.initials: GE
authors.lastname: Leverson
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Powell
authors.forename: Katelyn R
authors.initials: KR
authors.lastname: Richards
authors.forename: Anthony M
authors.initials: AM
authors.lastname: D'Alessandro
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lucey
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry*; D001706:Biopsy; D015935:Complement C4b / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D006680:HLA Antigens / Q000737:chemistry*; D006650:Histocompatibility Testing; D006801:Humans; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000276:immunology* / Q000628:therapy*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry; D011184:Postoperative Period; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D012306:Risk; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D000017:ABO Blood-Group System; D000906:Antibodies; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d