Late antibody-mediated rejection (AMR) is the major cause of renal allograft loss. Current research is focusing on identifying a performant risk stratification in order to guide intervention and prolong kidney survival.

We investigated graft outcome predictors in 24 nonsensitized pediatric kidney recipientspositive for HLA de novo donor specific antibodies (dnDSAs) and treated for late AMR with a combination of plasmapheresis, high IVIG and anti-CD20 MAb. Patients with graft dysfunction (clinical AMR) received 2 treatment courses, while those with subclinical AMR received a second treatment course in case of non response. Failure to remove DSAs, altered renal function and presence of C3d-binding DSAs were negatively associated to graft survival in the univariate analysis (p=0.01, p<0.001, p=0.005 respectively). Given the relevance of DSA removal for therapeutic success, we subsequently analyzed antibody characteristics dictating resistance to anti-humoral treatment. It was found that HLA DQ antigen specificity (odd ratio: 5.5, p=0.005), C3d (odd ratio: 23.1, p<0.001) binding ability, and high mean fluorescence intensity (odd ratio: 33.4, p<0.001) characterize DSAs scarcely susceptible to persistent removal; on the contrary, C1q positivity alone, i.e. .in the absence of C3d binding ability did not show any negative effect on dnDSA removal (odd ratio: 2.0, p=0.46). When looking at a validation cohort of dnDSA-positive patients treated preemptively, we observed 75% removal rate in comparison to 35% in the late AMR group, likely as a result of a more favourable biological profile of dnDSAs at onset. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to obtain stable dnDSA removal, and may be positively influenced by early/preemptive intervention.

CITATION INFORMATION: Nocera A., Cioni M., Tagliamacco A., Basso S., Innocente A., Fontana I., Magnasco A., Trivelli A., Gurrado A., Ramondetta M., Boghen S., Catenacci L., Verrina E., Garibotto G., Ghiggeri G., Cardillo M., Ginevri F., Comoli P. Failure to Remove De Novo Donor-Specific HLA Antibodies is Influenced by Antibody Properties and Identifies Kidney Recipients with Late Antibody-Mediated Rejection Destined to Graft Loss Am J Transplant. 2017;17 (suppl 3).

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