2010 - TTS International Congress


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Assays to Predict Allograft Rejection

112.4 - Early Post Transplant DeNovo HLA Antibodies Predict Decline in Lung Allograft Function at 18 months Post Transplant

Presenter: Ayesha, Haroon, ,
Authors: Haroon A., Singer L., Hwang D., Binnie M., Chaparro C., Chow C., DePerrot M., Pierre A., Waddell T., Yasufuku K., Azad S., Keshavjee S., Tinckam K.

EARLY POST TRANSPLANT DENOVO HLA ANTIBODIES PREDICT DECLINE IN LUNG ALLOGRAFT FUNCTION AT 18 MONTHS POST TRANSPLANT

ASSAYS TO PREDICT ALLOGRAFT REJECTION

A. Haroon1, L. Singer2, D.M. Hwang2, M. Binnie2, C. Chaparro2, C. Chow2, M. Deperrot2, A. Pierre2, T.K. Waddell3, K. Yasufuku2, S. Azad2, S. Keshavjee2, K. Tinckam4
1, University of TOronto, Toronto/CANADA, 2, University of Toronto, Toronto/CANADA, 3Thoracic Surgery, Toronto General Research Institute, Toronto/ON/CANADA, 4Hla Laboratory - Dept Of Laboratory Medicine, University Health Network, Toronto/CANADA

Body: Introduction: Both pre-and post transplant HLA antibodies (HLAAb) in isolation have been correlated with bronchiolitis obliterans syndrome (BOS) and graft failure in lung transplant, but the temporal relationship of post transplant HLAAb to clinically relevant outcomes is not well described. Methods: We conducted a retrospective review of 98 consecutive lung transplant from 11/06 to 12/07 with 3 month survival, who had protocol post transplant HLAAb testing q3mo for one year (solid phase, Luminex ™ platform).We examined the relationship of HLAAb development and presence to acute rejection (AR), diffuse alveolar damage (DAD), infections, radiographic findings, 6-minute walk, and pulmonary function tests at 3,6,9,12, and 18 months post transplant. C4d staining was not routinely performed in this cohort’s biopsies. Patients were divided into 3 groups for comparison: no HLAAb pre- or post-transplant (NoAb n=58), sensitized with HLAAb pre-tx (PreTxAb, n=18),and post-transplant de novo HLAAb (DNAb, n=22). The PreTxAb group received our standard high-risk protocol of perioperative plasma exchange, IVIg and MMF. Routine immunosuppression with CsA, azathioprine and prednisone was used for the remaining patients. Where appropriate, categorical variables were compared with Chi-squared or Fisher’s exact test, and continuous variables were compared using T-test, ANOVA, Kruskal-Wallis or Rank-sum tests. Results: Of 22 DNAb, 18 developed Ab at 3-6 months and 4 at 9-12 months. 18 month survival between the three groups was not statistically different (NoAb 86.2%; PreTxAb 94.4%, DNAb 77.2%, p=NS log-rank) Immunosuppression therapy was comparable between NoAb and DNAb groups. There was no association between de novo HLAAb or pre-transplant HLAAb and AR, DAD, infection, 6 minute walk, or XR findings at any timepoint. Early de novo HLAAb, and to a lesser extent pre-transplant HLAAb, were associated with decreased FEV1 at 18 months post-transplant to <80% of best FEV1 achieved (BOS-1). (Table) After adjusting for AR and CMV infection in the first year, early DNAb remained a significant predictor of BOS at 18 months post-transplant (OR 7.68:2.28-25.8).

Table. Impact of PostTx HLAAb on FEV1 Over Time
NoAb DNAb PreTxAb p
BOS-1 9m (% of recipients) (n=87 available) 18.0 (9/50) 25.0 (5/20) 23.0 (4/17) 0.71
BOS-1 12m (% of recipients) (n=83 available) 14.0 (7/50) 23.5 (4/17) 18.7 (3/16) 0.65
BOS-1 18m (% of recipients) (n=81 available) 18.6 (9/48) 70.6 (12/17) 37.5 (6/16) <0.001
% Best FEV1 9m (med:IQR) 93: 86-97% 88: 80-96% 94: 81-98% 0.57
% Best FEV1 12m (med:IQR) 96: 88-100% 92:82-96% 95 :84-99% 0.24
% Best FEV1 18m (med:IQR) 97: 86-100% 73: 65-87% 92:65-97% 0.0003

Conclusions: De novo HLAAb developed in 22% of pts in the first post transplant year, the majority in the first 3-6 months. This study demonstrates that pre-transplant HLAAb and the development of post-transplant de novo HLAAb, precedes and predicts subsequent decline in lung graft function 18 months after lung transplant, thus defining a potential window of opportunity for Ab specific interventions. Pre transplant HLAAb impact on FEV1 is lessened by an aggressive immunosuppressive protocol. BOS is a complex and multifactorial process, however these results support studies of early detection and treatment of de novo HLAAb to reduce the risk of this component of BOS.

Disclosure: All authors have declared no conflicts of interest.


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