2010 - TTS International Congress


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Assays to Predict Allograft Rejection

112.2 - Effect of Desensitization on DSA Strength and C4d Deposition

Presenter: Donna, Lucas, Baltimore, United States
Authors: Lucas D., Leffell M., Montgomery R., Warren D., Zachary A.

EFFECT OF DESENSITIZATION ON DSA STRENGTH AND C4D DEPOSITION

ASSAYS TO PREDICT ALLOGRAFT REJECTION

D.P. Lucas1, M.S. Leffell1, R.A. Montgomery2, D.S. Warren2, A.A. Zachary1
1Medicine, Johns Hopkins University, Baltimore/UNITED STATES OF AMERICA, 2Surgery, Johns Hopkins University, Baltimore/UNITED STATES OF AMERICA

Body: Introduction: Complement activation by donor-specific antibody (DSA), tested as C4d deposition in the Luminex antibody (Ab) assay, has shown to be associated with significantly reduced survival of heart transplants (Tx) compared to the presence of DSA alone (Smith, et al., 2007). Similar results have been shown for renal transplants (Wharmman et al. 2006). Nearly 50% of patients patients desensitized in our program have persistent DSA but many have long term graft survival. We examined sera from patients with persistent DSA to determine if in vitro C4d deposition correlated with clinical outcome. Methods: We examined sera from 40 renal transplant patients with persistent donor-specific antibody (DSA) following desensitization. Sera were tested from time points prior to and after desensitization, and at follow up (mean 10.3 months post transplantation) for changes in strength of antibody to donor or non-donor (third party) HLA and C4d deposition by either. Patients were grouped according to ratio as follows: Grp 1 - DSA and C4d increased; Grp 2 – DSA decreased, C4d increased; Grp 3 – DSA and C4d decreased. Sera were tested with single antigen panels on the Luminex platform according to the method of Smith, et al. (2007). Test values were normalized to account for inter-run differences in test sensitivity. Results: There were no differences among the groups in strength of initial crossmatch ( CDC vs FCXM), number of previous Tx, race, or gender. Group 1 had significantly more rejection episodes in the first year than did groups 2 and 3 (2.7, 1.75 and 1.3). There were no significant differences between the groups in creatinine values at one month (2.24, 1.46, 1.24, respectively) following desensitization (mean=52 days post-Tx). Serum creatinine values at follow up were significantly lower when DSA and C4d were decreased (1.26 mg/dL) vs. when C4d was increased, regardless of whether DSA was decreased (2.31) or not (2.33) (P = 0.03 for both). Notably, changes in strength of antibody or C4d were independent of specificity (class I or class II) and target (donor vs. third party antigen).
Conclusions: Antibody that persists after desensitization may or may not be deleterious to the graft. The data here show that when complement activation persists or increases, there is a long term negative impact on graft function, as measured by serum creatinine. Frequency of rejections in the first year was significantly higher (P = 0.03) in patients with increases in both DSA and C4d (group 1) than in patients with decreases in both (group 3). Group 2 was intermediate between groups 1 and 3, suggesting that even with a decrease in antibody an increase in complement binding is deleterious.

Disclosure: All authors have declared no conflicts of interest.


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