title: The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases.
abstract: We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.
authors.affiliation: Institut National de la Sante Et de la Recherche Medicale INSERM U643, and Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Brouard
authors.forename: A
authors.initials: A
authors.lastname: Pallier
authors.forename: K
authors.initials: K
authors.lastname: Renaudin
authors.forename: Y
authors.initials: Y
authors.lastname: Foucher
authors.forename: R
authors.initials: R
authors.lastname: Danger
authors.forename: A
authors.initials: A
authors.lastname: Devys
authors.forename: A
authors.initials: A
authors.lastname: Cesbron
authors.forename: C
authors.initials: C
authors.lastname: Guillot-Guegen
authors.forename: J
authors.initials: J
authors.lastname: Ashton-Chess
authors.forename: S
authors.initials: S
authors.lastname: Le Roux
authors.forename: J
authors.initials: J
authors.lastname: Harb
authors.forename: G
authors.initials: G
authors.lastname: Roussey
authors.forename: J-F
authors.initials: JF
authors.lastname: Subra
authors.forename: F
authors.initials: F
authors.lastname: Villemain
authors.forename: C
authors.initials: C
authors.lastname: Legendre
authors.forename: F J
authors.initials: FJ
authors.lastname: Bemelman
authors.forename: G
authors.initials: G
authors.lastname: Orlando
authors.forename: A
authors.initials: A
authors.lastname: Garnier
authors.forename: H
authors.initials: H
authors.lastname: Jambon
authors.forename: H
authors.initials: H
authors.lastname: Le Monies De Sagazan
authors.forename: L
authors.initials: L
authors.lastname: Braun
authors.forename: C
authors.initials: C
authors.lastname: Noël
authors.forename: E
authors.initials: E
authors.lastname: Pillebout
authors.forename: M-C
authors.initials: MC
authors.lastname: Moal
authors.forename: C
authors.initials: C
authors.lastname: Cantarell
authors.forename: A
authors.initials: A
authors.lastname: Hoitsma
authors.forename: M
authors.initials: M
authors.lastname: Ranbant
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: J-P
authors.initials: JP
authors.lastname: Soulillou
authors.forename: M
authors.initials: M
authors.lastname: Giral
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D007518:Isoantibodies