title: Polyreactive antibodies developing amidst humoral rejection of human kidney grafts bind apoptotic cells and activate complement.
abstract: Antibody mediated rejection (AMR) is associated with a variety of graft-reactive antibodies following kidney transplant. To characterize these antibodies, we immortalized 107 B cell clones from a patient with AMR. In a previous study, we showed that six clones were reacting to multiple self-antigens as well as to HLA and MICA for two of them, thus displaying a pattern of polyreactivity. We show here that all six polyreactive clones also reacted to apoptotic but not viable cells. More generally we observed a nearly perfect overlap between polyreactivity and reactivity to apoptotic cells. Functionally, polyreactive antibodies can activate complement, resulting in the deposition of C3d and C4d at the surface of target cells. Testing the serum of 88 kidney transplant recipients revealed a significantly higher IgG reactivity to apoptotic cells in AMR patients than in patients with stable graft function. Moreover, total IgG purified from AMR patients had increased complement activating properties compared to IgG from non-AMR patients. Overall, our studies show the development of polyreactive antibodies cross-reactive to apoptotic cells during AMR. Further studies are now warranted to determine their contribution to the detection of C4d in graft biopsies as well as their role in the pathophysiology of AMR.
authors.affiliation: Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: F
authors.initials: F
authors.lastname: Porcheray
authors.forename: J W
authors.initials: JW
authors.lastname: Fraser
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: A
authors.initials: A
authors.lastname: McColl
authors.forename: J
authors.initials: J
authors.lastname: DeVito
authors.forename: I
authors.initials: I
authors.lastname: Dargon
authors.forename: Y
authors.initials: Y
authors.lastname: Helou
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.forename: T C
authors.initials: TC
authors.lastname: Girouard
authors.forename: S L
authors.initials: SL
authors.lastname: Saidman
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: A
authors.initials: A
authors.lastname: Palmisano
authors.forename: U
authors.initials: U
authors.lastname: Maggiore
authors.forename: A
authors.initials: A
authors.lastname: Vaglio
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Zorn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood*; D015153:Blotting, Western; D016022:Case-Control Studies; D003167:Complement Activation / Q000276:immunology*; D015935:Complement C4b / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: Antibody-mediated rejection; C4d; apoptosis; polyreactive antibodies
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