P050 : CORRELATION OF THE PRESENCE OF COMPLEMENT BINDING DE NOVO DSA AND PATHOLOGY DEFINED ANTIBODY MEDIATED REJECTION (pAMR) IN HEART RECIPIENTS

Background Close monitoring of donor HLA specific antibody (DSA) strength and function is necessary to identify the risk for developing pAMR. Strongly binding DSAs tend to be complement binding as determined by the C1q binding on single antigen. The C1q binding assay detects more DSA than the complement dependent cytotoxicity (CDC) assay. The ability of a newly introduced assay for C3d binding to detect cytotoxic DSA and the correlation with CDC and C1q results is not known. Aim Our aim was to determine whether the detection of C3d binding DSA correlated with different pathology defined biopsy patterns among our heart recipient population. Methods Biopsy results with concurrent DSA analyses were reviewed for 28 heart recipients that were transplanted between 5/2003 and 7/2012. The biopsy AMR scores were graded by 2011 ISHLT guidelines according to the histopathologic and immunopathologic finding. The specificity and function of persistent de novo DSA was determined by LSA, C1q, C3d binding, and CDC panel. Levels of antibody to the non-HLA Angiotensin Type 1 receptor (AT1R) were determined in selected cases. Results Table 1 summarizes results of 15 samples tested by 4 antibody assays and corresponding pAMR scores. 12/15 (80%) sera showed C3d/C1q binding. 4/4 (100%) samples classified as pAMR2 had both C3d/C1q binding DSAs. 3/5 (60%) samples classified as AMR1 had both C3d/C1q binding DSAs. One AMR1 sample had only detectable C1q binding DSA. 4/5 (80%) AMR0 samples had both C3d/C1q binding DSAs. Three samples with strong levels of AT1R antibody (>17 units): two samples without C3d/C1q binding DSA had pAMR3 and pAMR1 respectively and one with DSAs and pAMR1. Conclusions The presence of LSA-C3d and LSA-C1q pos DSAs correlates with pathology defined pAMR in heart recipients. C3d/C1q DSAs were also identified with pAMR0. pAMR in the absence of DSA was associated with strong levels of AT1R antibody. Thus, both complement binding DSAs and non-HLA specific antibodies provide important insight into the antibody mediated rejection process. J. Kobashigawa: Grant/Research Support; Company/Organization; NIH ; N. Reinsmoen: Grant/Research Support; Company/Organization; Thermo/Fisher. Table 1. Summary of 15 C3d and C1q binding DSA testing results in relation to pAMR scores. pAMR Score Sample C3d DSA C1q DSA Consistency AT1r pAMR0 1 DQ2 DQ2 Yes 2 DQ2,7 DQ2,7 Yes 3 DQ2,7 DQ2,7 Yes 4 Neg DQ7 No 5 DR53 DR53, DQ8 No Strong pAMR1 6 Neg Neg Yes Strong 7 DR52, DQ7 DR52, DQ7 Yes 8 DR53, DQ5,6,7,8,9 DR53, DQ5,6,7,8,9 Yes 9 Neg DQ2 No 10 DQ5 DQ5 Yes pAMR2 11 DQ4 weak DQ4 Yes 12 DQ6 DQ6 Yes 13 DQ7 DQ7 Yes 14 DQ7,8 DQ7,8 Yes pAMR3 15 Neg Neg Yes Strong