title: The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients.
abstract: Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance.
authors.affiliation: 1 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.2 Department of Internal Medicine, Nephrology, University of Michigan, Ann Arbor, MI.3 Nephrology Department and Renal Transplant Unit, Hospital del Mar, Parc de Salut Mar, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.4 Heart and Lung Transplant Program, Department of Experimental and Specialty Medicine, Academic Hospital S. Orsola-Malpighi, University of Bologna, Bologna, Italy.5 Pathology Department, University of Pittsburgh Medical Center, Pittsburgh, PA.6 Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI.7 Transplantation Immunology, Department of Transfusion Medicine, Padua University Hospital, Padua, Italy.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: OʼLeary
authors.forename: Millie
authors.initials: M
authors.lastname: Samaniego
authors.forename: Marta Crespo
authors.initials: MC
authors.lastname: Barrio
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Arjang
authors.initials: A
authors.lastname: Djamali
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cozzi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016377:Organ Transplantation / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies