title: ABO incompatible renal transplants and decreased likelihood for developing immune responses to HLA and kidney self-antigens.
abstract: Immune responses to HLA and tissue-restricted self-antigens (SAgs) have been proposed to play a role in the pathogenesis of renal allograft (KTx) rejection. However, ABO incompatible (ABOi) KTx recipients (KTxR) following depletion of antibodies (Abs) to blood group antigens had fewer rejections. To determine the mechanisms, pre- and post-transplant sera from ABOi (n=18) and ABO-compatible (ABOc) (n=45) KTxR were analyzed for Abs against HLA class I and II by LABScreen single antigen assay. The development of Abs to SAgs was measured by ELISA. Immunity to Collagen IV (Col-IV) and cytokines induced were measured by ELISPOT. While 8/45 (18%) ABOc KTxR developed new donor specific antibodies to HLA (DSA) following transplantation, 0/18 ABOi KTxR developed DSA. ABOi KTxR failed to develop Abs to kidney SAgs (Col-IV and fibronectin (FN)). In contrast, 7 ABOc KTxR developed Abs to both Col-IV and FN. Col-IV stimulation of lymphocytes from ABOc KTxR demonstrated increased IFNγ, IL-17 and decreased IL-10. In contrast ABOi recipients following stimulation with antigens resulted in more IL10 and reduced IFN-γ and IL17 production. At one year, the GFR in ABOi KTxR were significantly better (p<0.04) than ABOc KTxR. De novo DSA and immune responses to SAgs are reduced or absent in ABOi KTxR which we propose leads to less acute rejection and better long term function following ABOi KTx.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Vijay
authors.initials: V
authors.lastname: Subramanian
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Muthukumar
authors.initials: M
authors.lastname: Gunasekaran
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Gaut
authors.affiliation: HLA Laboratory - Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Donna
authors.initials: D
authors.lastname: Phelan
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Neeta
authors.initials: N
authors.lastname: Vachharajani
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Rowena Delos
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Wellen
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Surendra
authors.initials: S
authors.lastname: Shenoy
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States. Electronic address: kumart@wustl.edu.
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D001787:Blood Group Incompatibility / Q000276:immunology*; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D005353:Fibronectins / Q000276:immunology; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008875:Middle Aged
chemical_list: D000906:Antibodies; D001324:Autoantigens; D024141:Collagen Type IV; D016207:Cytokines; D005353:Fibronectins; D006680:HLA Antigens
keywords: ABO compatibility; ABO incompatibility; Collagen-IV; DSA; Fibronectin; Renal transplantation