Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

作者：Roux A^*; Le Lan I Bendib; Holifanjaniaina S; Thomas K A; Hamid A M; Picard C; Grenet D; De Miranda S; Douvry B; Beaumont Azuar L; Sage E; Devaquet J; Cuquemelle E; Le Guen M; Spreafico R; Suberbielle Boissel C; Stern M; Parquin F

来源：American Journal of Transplantation, 2016, 16(4): 1216-1228.

DOI：10.1111/ajt.13589

• clinical research
• practice
• health services and outcomes research

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 (DSA(pos)AMR(pos)); (ii) DSA positive, AMR negative (DSA(pos)AMR(neg)); (iii) DSA limited, AMR negative (DSA(Lim); equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg)). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos)AMR(pos) (n=22), 40.3% were DSA(pos)AMR(neg) (n=84), 6% were DSA(Lim) (n=13) and 43% were DSA(neg) (n=88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos)AMR(pos) group (2.11.7) compared with DSA(pos)AMR(neg) (1 +/- 1.2), DSA(Lim) (0.75 +/- 1), and DSA(neg) (0.7 +/- 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dyshazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos)AMR(pos) 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.
The authors find an association between antibody-mediated rejection in lung transplantation and chronic lung allograft dysfunction and graft loss.

• 出版日期2016-4