The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies

Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid o...

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Main Authors: Edward J. Filippone, John L. Farber
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/5197396
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author Edward J. Filippone
John L. Farber
author_facet Edward J. Filippone
John L. Farber
author_sort Edward J. Filippone
collection DOAJ
description Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA mismatches. Determination of the pathogenicity of alloantibodies is evolving. Potential features include antibody strength (as assessed by antibody titer or, more commonly and inappropriately, mean fluorescence intensity) and ability to fix complement (in vitro by C1q or C3d assay or by IgG subclass analysis). Technical issues with the use of solid phase assays are also of prime importance, such as denaturation of HLA antigens and manufacturing and laboratory variability. Questions and controversies remain, and here we review new relevant data.
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spelling doaj-art-ec0087f08ee944d5a8b712a4abe2ffab2025-02-03T06:00:40ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/51973965197396The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA AntibodiesEdward J. Filippone0John L. Farber1Division of Nephrology, Department of Medicine, Sydney Kimmel School of Medicine, Thomas Jefferson University, Philadelphia, PA, USADepartment of Pathology, Sydney Kimmel School of Medicine, Thomas Jefferson University, Philadelphia, PA, USACentral to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA mismatches. Determination of the pathogenicity of alloantibodies is evolving. Potential features include antibody strength (as assessed by antibody titer or, more commonly and inappropriately, mean fluorescence intensity) and ability to fix complement (in vitro by C1q or C3d assay or by IgG subclass analysis). Technical issues with the use of solid phase assays are also of prime importance, such as denaturation of HLA antigens and manufacturing and laboratory variability. Questions and controversies remain, and here we review new relevant data.http://dx.doi.org/10.1155/2016/5197396
spellingShingle Edward J. Filippone
John L. Farber
The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies
Journal of Immunology Research
title The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies
title_full The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies
title_fullStr The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies
title_full_unstemmed The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies
title_short The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies
title_sort humoral theory of transplantation epitope analysis and the pathogenicity of hla antibodies
url http://dx.doi.org/10.1155/2016/5197396
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