G2(T)
DETECTION OF DONOR SPECIFIC ANTIBODIES PREDICTS ANTIBODY MEDIATED
REJECTION AND TRANSPLANT GLOMERULOPATHY
Willicombe, M, Brookes, P, Roufosse, C, Galliford, J, McLean, A, Cook, T, Cairns, T, Taube, D
Imperial College Kidney and Transplant Centre, London
BACKGROUND: Acute antibody mediated rejection [AMR] and transplant glomerulopathy [TG]
respectively, are the leading immunological causes of renal allograft loss.
AIMS: In this paper, we show that the early detection of donor specific antibodies [DSAbs] by single
antigen beads at the time of transplantation [preformed] or subsequently [de novo] predicts rejection,
both AMR and acute cellular rejection [ACR], TG and graft loss.
METHODS: We retrospectively analysed 469 patients [M:F 308:161, DD:LD 241:228,
1stgrafts:regrafts 412:57, mean HLA mismatch 3.23 ± 1.61] who received an ABO compatible renal
transplant.
All patients had a negative CDC and FCXM crossmatch at the time of transplantation and received
Alemtuzumab induction with a steroid sparing immunosuppressive regime. All patients’ sera were
tested pre and post transplant at 3 months and then at 6 monthly intervals or when clinically indicated
by Luminex methods.
RESULTS: 51/469 [10.9%] of patients were found to have preformed DSAbs and 74/418 [17.7%]
patients developed de novo DSAbs. Table 1 shows the 54 month event free survival in patients with
preformed DSAbs compared with DSAb- patients.
Allograft loss
Rejection
ACR
AMR
TG
DSAb+
85.8%
65.5%
89.9%
73.6%
87.7%
DSAb93.7%
79.6%
84.8%
91.4%
95.8%
p value
0.04
0.0069
0.38
<0.0001
0.0095
Table 2 shows the 54 month event free survival in de novo DSAb+ and DSAb- patients.
Allograft loss
Rejection
ACR
AMR
TG
DSAb+
85.0%
46.6%
72.1%
60.3%
80.8%
DSAb95.6%
86.9%
87.4%
98.2%
99.1%
p value
0.0006
<0.0001
0.0014
<0.0001
<0.0001
We calculated that detecting pre-transplant DSAb or de novo DSAb in the absence of allograft
dysfunction increases the risk of graft loss [OR: 3.49 (1.35-9.03), p=0.001], all rejection [OR:3.51
(2.09-5.88), p<0.0001], AMR [OR:19.02 (7.57-47.81), p<0.0001] and TG [OR:27.39 (7.95-94.36),
p<0.0001].
CONCLUSION: The identification of DSAbs at the time of transplant and their subsequent
development is a powerful predictor of rejection and graft loss. Not all patients with DSAbs develop
rejection and further work to determine which antibodies are pathogenic is in progress.
Risk stratification strategies should be developed to either avoid transplanting these patients, augment
their immunosuppression and facilitate informed consent.