Immunological risk stratification in highly sensitized transplant candidates: integrating molecular matching, crossmatching, donor selection, and desensitization

Highly sensitized transplant candidates continue to face significant barriers to transplantation because of pre-existing antibodies against donor HLA antigens. These patients often experience longer waiting times, reduced access to suitable donors, and a greater risk of antibody-mediated rejection following transplantation. While advances in histocompatibility testing have improved our ability to identify and characterize HLA antibodies and find more compatible donors, important questions remain regarding how best to assess immunological risk and translate laboratory findings into clinical decision-making.

In recent years, advances in molecular matching, epitope and eplet analysis, virtual crossmatching, and antibody assessment have opened new opportunities to better understand alloimmune risk. At the same time, desensitization strategies and novel therapeutic approaches continue to expand transplant opportunities for highly sensitized patients who previously had limited options.

This Research Topic aims to bring together clinicians, laboratory scientists, and researchers working across solid organ transplantation and immunogenetics to examine current and emerging approaches for immunological risk assessment, donor selection, achieving successful transplantation, and post-transplant management in highly sensitized transplant candidates. We welcome contributions addressing the following areas across all solid organs:

• Molecular and epitope-based HLA matching strategies for donor selection, acceptable mismatch identification, and individualized risk assessment
• Virtual and physical crossmatching, including interpretation of discrepant results and management of therapeutic antibody interference
• HLA and donor-specific antibody characterization and monitoring before and after transplantation, including dilution-based strength assessment, complement-binding assays, IgG subclasses, and thresholds for crossing preformed DSA
• Biomarkers of rejection risk, including integration of molecular and histologic markers
• Immunological risk surveillance strategies tailored to pre-transplant risk profiles
• Donor allocation strategies for sensitized candidates, including compatible allocation, kidney paired donation, and acceptable mismatch programs
• Desensitization strategies, from conventional protocols to emerging targeted therapies, and approaches to assessing treatment response and durability

We are particularly interested in studies that bridge laboratory discoveries with clinical practice and help advance a more personalized approach to transplant care.

Submissions may include original research articles, reviews, systematic reviews, perspective pieces, and translational studies involving kidney, heart, lung, liver, pancreas, and other solid organ transplantation settings. By integrating developments across HLA matching, antibody characterization, donor selection, and desensitization, this collection aims to improve access to transplantation while optimizing long-term graft outcomes for some of the most immunologically complex patients awaiting transplantation.