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

Abstract

Purpose of reviewThe 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 findingsRecent 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.SummaryHLA-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.

Lowering maintenance immune suppression in elderly kidney transplant recipients; connecting the immunological and clinical dots

“…Pre-transplantation DSA, also noncomplement binding and only detectable in the Luminex assay, constitutes an increased risk for ABMR early and even many years after transplantation, leading to an estimated excessive graft loss of approximately 10-15% at 10 years (134, 135). Why the majority of DSA are not causing clinically relevant ABMR and/or graft loss is not well known but may relate to the affinity, complement binding capacity, and glycosylation profile of the antibodies (136)(137)(138). The current knowledge is insufficient to accurately predict which recipient with, e.g., a fully HLA-mismatched kidney transplant, will experience rejection and who will not.…”

Editorial: Mechanistic and therapeutic advances in antibody-mediated rejection: reasons to be optimistic

“…Although DSA are associated with a higher risk of poor graft outcomes, there is a wide range of scenarios that can follow DSA detection, from asymptomatic to the development of severe acute ABMR leading to early graft loss. In this issue, Louis and Lefaucheur [4] review recent improvements in DSA characterization that extend beyond antibody quantification and include affinity, epitope specificity, immunoglobulin G subclasses and complement-binding capacity. The authors also discuss the clinical importance of DSA as a biomarker for immune risk assessment in the pretransplant period, for the diagnosis and treatment evaluation of ABMR, as well as for immune monitoring and risk stratification after transplantation.…”