title: Donor-specific antibodies accelerate arteriosclerosis after kidney transplantation.
abstract: In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n=40) or without (n=59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 ± 0.11 to 1.12 ± 0.10, P=0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 ± 0.11 to 0.81 ± 0.10, P=not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donor-specific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.
authors.affiliation: Laboratoire d’Anatomie Pathologique, Hôpital Européen Georges Pompidou, APHP, Paris, France. garyhillparis@aol.com
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hill
authors.forename: Dominique
authors.initials: D
authors.lastname: Nochy
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: J P
authors.initials: JP
authors.lastname: Duong van Huyen
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.forename: Julien
authors.initials: J
authors.lastname: Zuber
authors.forename: Dany
authors.initials: D
authors.lastname: Anglicheau
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Empana
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loupy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D001161:Arteriosclerosis / Q000209:etiology*; D001706:Biopsy; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008875:Middle Aged; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies