title: Pretransplant IgG reactivity to apoptotic cells correlates with late kidney allograft loss.
abstract: Preexisting serum antibodies have long been associated with graft loss in transplant recipients. While most studies have focused on HLA-specific antibodies, the contribution of non-HLA-reactive antibodies has been largely overlooked. We have recently characterized mAbs secreted by B cell clones derived from kidney allograft recipients with rejection that bind to apoptotic cells. Here, we assessed the presence of such antibodies in pretransplant serum from 300 kidney transplant recipients and examined their contribution to the graft outcomes. Kaplan-Meier survival analysis revealed that patients with high pretransplant IgG reactivity to apoptotic cells had a significantly increased rate of late graft loss. The effect was only apparent after approximately 1 year posttransplant. Moreover, the association between pretransplant IgG reactivity to apoptotic cells and graft loss was still significant after excluding patients with high reactivity to HLA. This reactivity was almost exclusively mediated by IgG1 and IgG3 with complement fixing and activating properties. Overall, our findings support the view that IgG reactive to apoptotic cells contribute to presensitization. Taking these antibodies into consideration alongside anti-HLA antibodies during candidate evaluation would likely improve the transplant risk assessment.
authors.affiliation: Transplant Center, The First Hospital of Jilin University, Changchun, China; Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: C
authors.initials: C
authors.lastname: Moore
authors.forename: F
authors.initials: F
authors.lastname: Porcheray
authors.forename: C
authors.initials: C
authors.lastname: Rong
authors.forename: C
authors.initials: C
authors.lastname: Abidoglu
authors.forename: J
authors.initials: J
authors.lastname: DeVito
authors.forename: R
authors.initials: R
authors.lastname: Paine
authors.forename: T C
authors.initials: TC
authors.lastname: Girouard
authors.forename: S L
authors.initials: SL
authors.lastname: Saidman
authors.forename: D
authors.initials: D
authors.lastname: Schoenfeld
authors.forename: B
authors.initials: B
authors.lastname: Levin
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.forename: N
authors.initials: N
authors.lastname: Elias
authors.forename: C
authors.initials: C
authors.lastname: Schuetz
authors.forename: I
authors.initials: I
authors.lastname: Rosales
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.forename: E
authors.initials: E
authors.lastname: Zorn
mesh_terms: D064591:Allografts; D017209:Apoptosis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D019169:Jurkat Cells; D007676:Kidney Failure, Chronic / Q000401:mortality* / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G
keywords: Anti-apoptotic cell antibodies; apoptotic cells; complement; graft loss; kidney transplantation; sensitization