title: Prevalence and specificity of immunoglobulin G and immunoglobulin A non-complement-binding anti-HLA alloantibodies in retransplant candidates.
abstract: The role of complement-binding donor-directed anti-human leukocyte antigen (HLA) antibodies in graft rejection is well established, whereas the prevalence and relevance of non-complement-binding (NCB) anti-HLA antibodies are less well defined. The aim of our study was to establish a sensitive and reliable test system for the detection and the specification of these NCB anti-HLA antibodies. Sera from 60 patients awaiting retransplantation were analysed for the presence of anti-HLA class I alloantibodies with complement-dependent cytotoxicity (CDC) tests. Immunoglobulin (Ig)G(all) anti-HLA class I and class II alloantibodies were differentiated on generic level by plate-based solid phase enzyme-linked immunosorbent assay. Subsequently, a modified bead-based (Luminex) assay was applied, allowing the investigation of IgG(2/4) NCB isotypes as well as IgA(1/2). The anti-HLA specificities of the NCB alloantibodies were determined and compared with known mismatches from previous transplants. Seventeen of the 60 sera (28%) were positive in the CDC increasing to 26 of 60 (43%) in the class I and 33 of 60 (55%) in the class II plate-based assay. Using the modified bead-based system 24 of 60 sera (40%) contained NCB IgG(2/4), which were mostly donor specific. In addition, a high prevalence of NCB IgA antibodies was detected (26 of 60 sera), which occurred independently of IgG(2/4) NCB, and half of which were donor specific. NCB anti-HLA alloantibodies, including the IgA isotype, can reliably be detected using the modified bead-based test system. These NCB alloantibodies had a high prevalence in retransplant candidates and were mostly donor specific.
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nürnberg, Erlangen, Germany. marlies.arnold@uk-erlangen.de
authors.forename: M-L
authors.initials: ML
authors.lastname: Arnold
authors.forename: M
authors.initials: M
authors.lastname: Dechant
authors.forename: I I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: B M
authors.initials: BM
authors.lastname: Spriewald
mesh_terms: D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D007518:Isoantibodies / Q000097:blood / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D012086:Reoperation
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007518:Isoantibodies; D003165:Complement System Proteins