TY - JOUR
T1 - Antibody-Mediated Rejection in Lung Transplantation
T2 - Clinical Outcomes and Donor-Specific Antibody Characteristics
AU - Roux, A.
AU - Bendib Le Lan, I.
AU - Holifanjaniaina, S.
AU - Thomas, K. A.
AU - Hamid, A. M.
AU - Picard, C.
AU - Grenet, D.
AU - De Miranda, S.
AU - Douvry, B.
AU - Beaumont-Azuar, L.
AU - Sage, E.
AU - Devaquet, J.
AU - Cuquemelle, E.
AU - Le Guen, M.
AU - Spreafico, R.
AU - Suberbielle-Boissel, C.
AU - Stern, M.
AU - Parquin, F.
N1 - Publisher Copyright:
© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d+ staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSAposAMRpos); (ii) DSA positive, AMR negative (DSAposAMRneg); (iii) DSA limited, AMR negative (DSALim; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSAneg). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSAposAMRpos (n = 22), 40.3% were DSAposAMRneg (n = 84), 6% were DSALim (n = 13) and 43% were DSAneg (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSAposAMRpos group (2.1 ± 1.7) compared with DSAposAMRneg (1 ± 1.2), DSALim (0.75 ± 1), and DSAneg (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSAposAMRpos patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.
AB - In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d+ staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSAposAMRpos); (ii) DSA positive, AMR negative (DSAposAMRneg); (iii) DSA limited, AMR negative (DSALim; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSAneg). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSAposAMRpos (n = 22), 40.3% were DSAposAMRneg (n = 84), 6% were DSALim (n = 13) and 43% were DSAneg (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSAposAMRpos group (2.1 ± 1.7) compared with DSAposAMRneg (1 ± 1.2), DSALim (0.75 ± 1), and DSAneg (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSAposAMRpos patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.
UR - http://www.scopus.com/inward/record.url?scp=84959378148&partnerID=8YFLogxK
U2 - 10.1111/ajt.13589
DO - 10.1111/ajt.13589
M3 - Article
C2 - 26845386
AN - SCOPUS:84959378148
SN - 1600-6135
VL - 16
SP - 1216
EP - 1228
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 4
ER -