OR16 Donor-specific antibodies (DSA) detected by C1Q and C3D assays predict antibody-mediated rejection (AMR) in renal transplant (TX) patients, but specific detection of IGG2, IGG3, IGG4, IGA, and IGM DSA, and ANTI-AT1R and anti-etar antibodies do not

Abstract

Aim To investigate the specific roles for Class I and Class II DSA, complement binding and activation, and non-HLA antibodies, in renal tx patients with AMR. Methods One Lambda®: LABScreen™ (routine total IgG and modified to detect IgG1, IgG2, IgG3, IgG4, IgA, IgM); C1qScreen™; anti-AT1R; anti-ETAR. Immucor®: LIFECODES C3d. Assays were used to detect the presence of antibodies and DSA. The quantity of each antibody and capacity to bind and activate complement were correlated with the histopathologic features found in biopsy specimens. Among 480 renal transplants performed between 2009 and 2014, we enrolled 17 (∼4%) patients with clinical and histopathologic diagnosis of AMR, and compared with matched-controls who had anti-HLA antibodies and apparent DSA, but had not exhibited AMR. We assessed antibodies and DSA MFI values prior to transplantation and at the time of AMR. Results Detection of anti-AT1R, anti-ETAR, and Class I DSA did not correlate with AMR. Class II IgG2, IgG3, IgG4, IgA, and IgM DSA did not correlate with AMR. Class II DSA >500 MFI detected by LABScreen™ + C1q + IgG1 + C3d identified 82% of patients and only 12% of controls, p = 0.00009 (88% PPV, 17% NPV), whereas, C1q + C3d identified 71% of patients and no controls, p = 0.00002 (100% PPV, 23% NPV). Notable is that anti-HLA Class II DSA detected by C1q and C3d correlates with rejection, and the injury found on biopsies was primarily tubulointerstitial, consistent with the region where constitutive expression of HLA Class II occurs in renal tissue. Conclusions Clinically “reversible” AMR appears to be due to Class II anti-HLA DSA, which can bind and activate complement. Detection of anti-HLA DSA by the C1q and C3d assays correlate with histological characteristics (tubulointerstitial injury) of AMR in renal allografts, and indicates that monitoring for anti-HLA DSA, which can bind and activate complement, may be useful to detect patients at risk for AMR; thus allowing for earlier detection and treatment prior to graft injury or graft loss.