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2016 ; 100
(1
): 39-53
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The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific
HLA Antibody Production in Solid Organ Transplant Recipients
#MMPMID26680372
O?Leary JG
; Samaniego M
; Barrio MC
; Potena L
; Zeevi A
; Djamali A
; Cozzi E
Transplantation
2016[Jan]; 100
(1
): 39-53
PMID26680372
show ga
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.
|*Histocompatibility
[MESH]
|Animals
[MESH]
|Biomarkers/blood
[MESH]
|Drug Therapy, Combination
[MESH]
|Graft Rejection/blood/immunology/*prevention & control
[MESH]
|Graft Survival/drug effects
[MESH]
|HLA Antigens/*immunology
[MESH]
|Histocompatibility Testing
[MESH]
|Humans
[MESH]
|Immunosuppressive Agents/adverse effects/*therapeutic use
[MESH]