Jeffrey J Kiernan1, Cynthia A Ellison1,2, Kathryn J Tinckam1,3,4,2. 1. Regional HLA Laboratory, Laboratory Medicine Program, University Health Network. 2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. 3. Division of Nephrology, University Health Network. 4. Department of Medicine, University of Toronto.
Abstract
PURPOSE OF REVIEW: This review describes the utility and limitations of measure for assessing the presence, relative strength, and clinical impact of human leukocyte antigen (HLA) alloantibodies, as well as the other qualitative features of antibodies that are important considerations in assessing patient risk. RECENT FINDINGS: Using MFI as a measure of antibody amount is limited for a variety of reasons. Standardized serum manipulations such as ethylene-diamine-tetra-acetic acid treatment or serum dilution results in better definition of relationships between MFI and antibody titer or complement activation, toward greater alignment in defining positivity. Increased understanding of HLA epitopes has improved the ability to precisely define donor specific HLA antibody (DSA) specificities and the analysis of structural HLA Class II epitope mismatches in donor-recipient pairs may assist in the prevention of de novo DSA development. Studies of antibody isotypes and immunopathological mechanisms underlying graft injury mediated by non-HLA antibodies are expanding the assessemnt of immunological risk. SUMMARY: Careful analysis of both semiquantitative and qualitative properties of donor-specific antibodies continues to improve our ability to study the effects of DSA on clinical outcomes in solid organ transplantation.
PURPOSE OF REVIEW: This review describes the utility and limitations of measure for assessing the presence, relative strength, and clinical impact of human leukocyte antigen (HLA) alloantibodies, as well as the other qualitative features of antibodies that are important considerations in assessing patient risk. RECENT FINDINGS: Using MFI as a measure of antibody amount is limited for a variety of reasons. Standardized serum manipulations such as ethylene-diamine-tetra-acetic acid treatment or serum dilution results in better definition of relationships between MFI and antibody titer or complement activation, toward greater alignment in defining positivity. Increased understanding of HLA epitopes has improved the ability to precisely define donor specific HLA antibody (DSA) specificities and the analysis of structural HLA Class II epitope mismatches in donor-recipient pairs may assist in the prevention of de novo DSA development. Studies of antibody isotypes and immunopathological mechanisms underlying graft injury mediated by non-HLA antibodies are expanding the assessemnt of immunological risk. SUMMARY: Careful analysis of both semiquantitative and qualitative properties of donor-specific antibodies continues to improve our ability to study the effects of DSA on clinical outcomes in solid organ transplantation.