Abstract
The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1604-1614 |
| Number of pages | 11 |
| Journal | American Journal of Transplantation |
| Volume | 18 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2018 |
Funding
Renata Albrecht (US Food and Drug Administration), Nancy Bridges (National Institutes of Health, National Institute of Allergy and Infectious Diseases), and Mark Aeder (United Network for Organ Sharing). Subgroups were charged with providing educational primers on (1) the definition and use of HLA diagnostic testing and (2) the biological basis of immunologic naD?veté versus memory. Orgasnp-ecific groups were tasked to establish criteria to assess patients’ risk in the context of a naD?ve-rsus-memory immunologic response and to use this distinction to inform HLA diagnostic use pretransplant and posttransplant. Initial recommendations were formulated, followed by face-to-face deliberations of the full group on February 26, 2017, at the Arizona Biltmore Hotel in Phoenix, Arizona. Importantly, subgroups were asked to identify key knowledge gaps that, if addressed, could significantly advance clinical practice. Representatives from the US Food and Drug Administration (FDA), National Institutes of Health (NIH), and the United Network for Organ Sharing (UNOS) attended as observing stakeholders. It should be noted that the STAR Working Group refrained from specific recommendations for therapeutic protocols for 2 major reasons: (1) high-quality evidence is lacking to support one approach over another, and (2) for a given patient, the risk of memory or de novo alloimmunity, and the requirements for risk mitigation therapies, varies significantly based on the target organ (most notably in the case of liver transplants). Logistics: Victoria Convers, Anthony Celenza (Association Headquarters). Sponsors: American Society for Histocompatibility and Immunogenetics, American Society of Transplantation, Canadian Blood Services, Canadian Society of Transplantation, Immucor, International Society for Heart and Lung Transplantation, Mark Terasaki and Laurinda Jaffe in memory of Paul I. Terasaki, National Institute of Allergy and Infectious Diseases, and One Lambda | A Thermo Fisher Scientific Brand.
Keywords
- alloantibody
- clinical research/practice
- clinical trial design
- guidelines
- histocompatibility
- immunobiology
- monitoring: immune
- sensitization
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)