DSA in solid organ transplantation: is it a matter of specificity, amount, or functional characteristics?

ABSTRACT

PURPOSE OF REVIEW The present review describes the clinical relevance of human leukocyte antigen (HLA) donor-specific antibodies (HLA-DSAs) as biomarkers of alloimmunity and summarizes recent improvements in their characterization that provide insights into immune risk assessment, precision diagnosis, and prognostication in transplantation. RECENT FINDINGS: Recent studies have addressed the clinical utility of HLA-DSAs as biomarkers for immune risk assessment in pretransplant and peritransplant, diagnosis and treatment evaluation of antibody-mediated rejection, immune monitoring posttransplant, and risk stratification. SUMMARY: HLA-DSAs have proved to be the most advanced immune biomarkers in solid organ transplantation in terms of analytical validity, clinical validity and clinical utility. Recent studies are integrating multiple HLA-DSA characteristics including antibody specificity, HLA class, quantity, immunoglobulin G subclass, and complement-binding capacity to improve risk assessment peritransplant, diagnosis and treatment evaluation of antibody-mediated rejection, immune monitoring posttransplant, and transplant prognosis evaluation. In addition, integration of HLA-DSAs to clinical, functional and histological transplant parameters has further consolidated the utility of HLA-DSAs as robust biomarkers and allows to build new tools for monitoring, precision diagnosis, and risk stratification for individual patients. However, prospective and randomized-controlled studies addressing the clinical benefit and cost-effectiveness of HLA-DSA-based monitoring and patient management strategies are required to demonstrate that the use of HLA-DSAs as biomarkers can improve current clinical practice and transplant outcomes.