Sensitization in heart transplantation — the expression of circulating antibodies against a potential donor — presents challenges for heart transplant recipients and physicians, concludes a scientific statement from the American Heart Association (AHA) summarizing emerging knowledge in the field.
Sensitization in transplantation "remains a limitation to access to heart transplant, increases waiting time, and sometimes even excludes patients from transplant," Monica Colvin, MD, chair of the writing group, told theheart.org | Medscape Cardiology.
Current management strategies for sensitization in heart transplantation have yet to be standardized, and current therapies have yielded "inconsistent results," said Colvin, director of heart transplant research at the University of Michigan in Ann Arbor.
The statement was published online February 19 in Circulation. It has been endorsed by the International Society for Heart and Lung Transplantation.
Based on the latest scientific data and consensus, the writing group offers a number of "clinical pearls" on detection and management of sensitization in heart transplantation.
They note that close to 20% of heart transplant candidates have a panel of reactive antibodies (PRA) consistent with sensitization. Any level of detectable antibody may be considered sensitization; however, common thresholds for desensitization therapies are PRA greater than 25% or calculated PRA (cPRA) greater than 50%, the statement notes. Sensitization can occur through antigenic exposure or viral infection and as a result of genetic predisposition.
Antibody screening methods vary in sensitivity and specificity, the authors note. Percent PRA is imprecise, dependent on panel cell construction, not standardized, and not representative of the true donor pool. For these reasons, specificity is now required to determine a cPRA, and the term PRA is now largely obsolete, the statement says.
It advises Luminex-based assays, especially with single-antigen beads (SABs), as the preferred method for pretransplantation and posttransplantation screening, identification, and monitoring of antibodies for all 11 human leukocyte antigen (HLA) loci.
Additional testing, such as IgG titers, complement-binding assays, and IgG subtyping assays, can be useful — and often is needed to determine the clinical significance of detected donor-specific HLA antibodies (DSAs), the statement says.
Based on the evidence, sensitization to HLA class I and class II antibodies confers a higher risk of rejection and cardiac allograft vasculopathy (CAV) and increases waiting time for heart transplant candidates. Patients exhibiting a positive pretransplantation crossmatch to donor HLA are at high risk for rejection and mortality. Avoiding a positive crossmatch and using measures to reduce preformed antibodies may be beneficial in improving posttransplantation outcomes, the authors report.
The writing group emphasizes that there are numerous gaps in evidence-based medical management of the sensitized patient and that much of the current knowledge about management stems from the renal transplant literature.
"Although current strategies involve antibody suppression and removal with intravenous immunoglobulin, plasmapheresis, and antibody therapy, newer strategies with more specific targets are being investigated," they write.
"Studies are underway to evaluate newer antibody therapy, such as eculizumab (Soliris, Alexion Pharmaceuticals); however, these therapies are expensive and heart transplant trials are frequently difficult to enroll and limited by sample size," Colvin told theheart.org | Medscape Cardiology.
She also noted that questions remain on the timing of desensitization therapies and how to manage sensitized patients with left ventricular assist devices.
In an online commentary, Donna Mancini, MD, Department of Cardiology, Icahn School of Medicine at Mount Sinai in New York City, notes that heart transplantation is an "evolving field."
"Nowhere is that more evident than in the identification and management of HLA and non-HLA antibodies in heart transplant candidates and recipients," she said. "With the development of new sensitive techniques which identify HLA antibodies in patient sera, there has been both a simplification of, and an added complexity to, patient management."
Mancini said the extensive review of allosensitization by Colvin and colleagues "serves as an educational tool for all practitioners."
Colvin and Mancini have disclosed no relevant financial relationships. Disclosures for writing group members are listed with the original article.
Circulation. Published online February 19, 2019. Abstract, Editorial
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