Humoral allo-immunity is a major determinant of kidney graft survival, and de novo donor specific anti-HLA antibodies (dnDSA) are associated with an increased risk of graft dysfunction and graft loss. Recent reports support the hypothesis that acute rejection may trigger dnDSA appearance. However, graft prognosis is not impaired by T-cell mediated rejection (TCMR). This discrepancy let us to conduct a longitudinal cohort study to explore dnDSA appearance after an episode of TCMR.
We considered all adequate kidney graft biopsies performed in our institution from 09/01/04 to 12/31/10 (n=3204). High immunological-risk kidney transplant recipients (graft rank>1, pre-transplantation DSAs, PRA>80%) and multi-organ recipients were excluded. We then selected biopsies meeting Banff Classifications TCMR criteria (n=97). Luminex was used to monitor patients for presence of anti-HLA antibodies. Positive sera were subsequently tested by luminex single antigen assays to determine specificities. Absence of DSA before the TCMR event was defined by (i) one negative anti-HLA Ab screening before the TCMR; (ii) the absence of DSA in case of positive screening before the TCMR; (iii) or two negative screenings after the TCMR, considering that spontaneous DSA disappearance is a rare occurrence.
We identified 75 non-sensitized patients with TCMR history eligible for this study. Median recipient age at transplantation was 50 years old (range: 22-77). Sex ratio (M/F) was 4.36/1 and 29% of grafts came from living donors. TCMR was subclinical in 40% of cases. Distribution of acute TCMR grades was 12 IA (16%), 35 IB (47%), 21 IIA (28%), 4 IIC (5%) and 3 III (4%) according to Banff Classification, and TCMR occurred a median time of 3.0 months post transplantation (0.2-46.3). Only three patients (4%), 2 with grade IB and 1 with grade IIB TCMR, developed dnDSA within one year after TCMR at 1.7, 11 and 11 months after TCMR.
We did not observe an incidence peak of dnDSA appearance within a year after TCMR in non-sensitized patients. Consequently, TCMR does not seem to trigger humoral allo-immunity in kidney transplant recipients. These results are consistent with the lack of impact of TCMR on long-term graft survival.
To cite this abstract in AMA style:Chemouny J, Suberbielle C, Loupy A, Legendre C, Anglicheau D. T-Cell Mediated Rejections Do Not Induce De Novo Donor Specific Antibodies in Non-Sensitized Kidney Transplant Recipients: A Longitudinal Cohort Analysis [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/t-cell-mediated-rejections-do-not-induce-de-novo-donor-specific-antibodies-in-non-sensitized-kidney-transplant-recipients-a-longitudinal-cohort-analysis/. Accessed September 23, 2017.
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