title: HLA class II DQA and DQB epitopes: recognition of the likely binding sites of HLA-DQ alloantibodies eluted from recombinant HLA-DQ single antigen cell lines.
abstract: Donor-specific antibodies (DSA) in sera of sensitized transplant patients are often produced against the specific epitopes on mismatched HLA antigens. In this study, we selected sera from 30 kidney transplant patients with DSA and AMR to define DQ epitopes. Using adsorption and elution assays, we identified 18 antibody reaction patterns to define 6 new epitopes and to confirm 12 previously defined epitopes. In one patient case, one mismatched antigen produced 3 different antibodies and, in another, antibodies were produced against the alpha and beta chains of the same antigen. For some sera, a single epitope can explain reactions for 27 of the 29 DQ beads in the single antigen panel. Several studies highlighted the prevalence of anti-DQ antibodies. In 2011, Almeshari et al. observed DQ DSA in 34/46 (74%) of rejection episodes - 44 patients had DSA and 20 lost their graft due to AMR. Other studies have shown a high prevalence of anti-DQ antibodies and an association with adverse effects on the graft. We conclude that analysis of the epitopes of the DQ antibodies using Adsorption/Elution and testing on single antigen DQ beads helps to better understand the specificities and cross-reactions of DQ antibodies in transplant patients.
authors.affiliation: One Lambda Inc., Canoga Park, CA, USA. nelawar@onelambda.com
authors.forename: Nadim
authors.initials: N
authors.lastname: El-Awar
authors.forename: Anh
authors.initials: A
authors.lastname: Nguyen
authors.forename: Khalid
authors.initials: K
authors.lastname: Almeshari
authors.forename: Moheeb
authors.initials: M
authors.lastname: Alawami
authors.forename: Fadi
authors.initials: F
authors.lastname: Alzayer
authors.forename: Maha
authors.initials: M
authors.lastname: Alharbi
authors.forename: Nori
authors.initials: N
authors.lastname: Sasaki
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D017951:Antigen Presentation; D001666:Binding Sites, Antibody / Q000235:genetics; D002460:Cell Line; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology* / Q000302:isolation & purification; D006084:Graft Rejection / Q000276:immunology*; D059848:HLA-DQ alpha-Chains / Q000235:genetics / Q000276:immunology*; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation; D011183:Postoperative Complications / Q000276:immunology*; D011485:Protein Binding; D019076:Transgenes / Q000235:genetics
chemical_list: D018985:Epitopes, B-Lymphocyte; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D007518:Isoantibodies
keywords: AMR; Adsorption/Elution; DQ alpha chain; DQ beta chain; DQA; DQB; DSA; PBS; RT; SA; TG; adsorbed and eluted; antibody-mediated rejection; donor-specific antibody; phosphate buffered saline; rHLA; recombinant HLA cell line; room temperature, MFI, mean fluorescence intensity; single antigen; transplant glomerulopathy