Authors:
A. BASIRE (Marseille, FR)
M. Reynaud-Gaubert (Marseille, FR)
A. Loundou (Marseille, FR)
J. DI CRISTOFARO (Marseille, FR)
P. PAULE (Marseille, FR)
M. PELARDY (Marseille, FR)
L. LYONNET (Marseille , FR)
C. FRASSATI (Marseille, FR)
P. Thomas (Marseille, FR)
C. Gomez (Marseille, FR)
C. PICARD (MARSEILLE, FR)
We investigated the impact of C1q binding to de novo HLA Donor Specific Antibodies (DSA) on the mortality and the occurrence of chronic rejection (CLAD) in 192 Lung transplantation (LTx) recipients from the Marseille Lung Transplant Center between December 2006 and December 2013 and with at least 30-day survival. Complement-binding antibodies were detected retrospectively for patients with de novo DSA at M1 and M3 after LTx, using the C1q Luminex assays. CD16 engagement were assessed within PBMC effector cells by flowcytometry analysis of the decrease of MFI CD16 at the surface of CD3-CD56 NK cell subsets exposed to allogeneic target cells in presence of DSA.
During the study period, 45 LTx recipients developed CLAD (including 8 patients (17%) with RAS and 39 (83 %) with bronchiolitis obliterans) and median overall survival was 35 (+/- 30) months. DSA were detected in 31% of LTx at M1 and 18% at M3. The cumulative DSA MFI (cMFI) level of de novo DSA at M1 were not associated to persistence of DSA at M3 (p=0.40). ROC curve analysis showed that DSA MFI threshold >17,000 was associated with death with 50% sensitivity and 85% specificity. Only DSA at M3 were associated with lower survival (p=0.02) and CLAD occurrence (p=0.01). C1q bound 52% and 33% of DSA at M1 and M3, respectively. Among ten C1q+DSA at M3, eight C1q+ DSA were persistent and two were de novo DSA. The cMFI value of DSA at M1> 10,500 were correlated with C1q binding with 89% sensitivity and 69% specificity. C1q DSA at M1 and M3 were not correlated with clinical occurrence. Interesting, the engagement of CD16 by LTx DSA were very low whatever the MFI intensity, the time after LTx and the clinical occurrence.
Finally, these data show that biochemical and biophysical characteristics of LTx DSA are different to these of DSA in other organ transplantation. They should be confirmed by another larger LTx cohort.