Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance.
Solid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panel-reactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.
Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Eva
E
Svobodova
Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Tomas
T
Gazdic
Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Milos
M
Kubanek
Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Jevgenija
J
Vymetalova
Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Ludek
L
Voska
Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Martin
M
Kment
Department of Biostatistics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Vera
V
Lanska
Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Libor
L
Kolesar
Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Marian
M
Urban
Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Ivan
I
Netuka
Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Jan
J
Pirk
Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Vojtech
V
Melenovsky
Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Josef
J
Kautzner
Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Antonij
A
Slavcev
Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Ivan
I
Malek
D000328:Adult; D000704:Analysis of Variance; D000918:Antibody Specificity; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000097:blood* / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007114:Immunization / Q000379:methods; D007165:Immunosuppression Therapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D014181:Transplantation Immunology / Q000502:physiology*; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
D006680:HLA Antigens
antibody-mediated rejection; heart transplantation; human leukocyte antigens antibodies; prognosis