title: De novo development of antibodies to kidney-associated self-antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children.
abstract: Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self-antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney-associated self-antigens develop following pediatric renal transplantation. We investigated post-transplant development of Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney-associated self-antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post-transplant. No samples had Abs to kidney-associated self-antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney-associated self-antigen post-transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation--a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Hesemann
authors.affiliation: Department of Surgery, Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Subramanian
authors.affiliation: Department of Surgery, Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Vikas R
authors.initials: VR
authors.lastname: Dharnidharka
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000276:immunology*; D006084:Graft Rejection; D006801:Humans; D007223:Infant; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D011184:Postoperative Period; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D051437:Renal Insufficiency / Q000097:blood / Q000276:immunology* / Q000601:surgery; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D005353:Fibronectins; D044140:Receptor, Angiotensin, Type 1
keywords: autoantibody; chronic rejection; renal transplantation