Renal transplant recipients with negative CDC [CDC-XM] and Flow crossmatch [Flow-XM] and low level DSA [by Luminex] have worse outcomes than non-sensitized patients. The aim of this study was to confirm, using C1qScreen™, the results of our previous study, using C4d beads, showing that the ability of preformed DSA to activate the classical pathway of complement dictates pathogenicity and predicts acute rejection.
52 patients [23m:29f, age 48.3±11.8 years, 29 deceased: 23 live donor, 28 first graft: 24 subsequent grafts] had preformed DSA detected by Luminex. 25 had class I DSA, 19 class II, and 8 both class I and class II. Mean fluorescent intensity [MFI] of the sum of DSA was 3152±2922. All patients were T and B cell CDC and T cell Flow-XM negative and all received a steroid-sparing regimen of alemtuzumab, one week of steroids and tacrolimus.
Pre-transplant sera were retested with the commercially available C1qScreen™ assay using Phycoerythrin-labelled anti-C1q antibody to detect C1q bound to the Fc portion of anti-HLA IgG on microbeads.
One or more complement fixing anti-HLA antibodies were detected in 22/52 [42%] patients, 6 class I, 9 class II and 7 with both class I+II. 12/52 patients had C1q positive DSA [C1q+DSA], 10/52 patients had C1q positive third party, non DSA, anti-HLA antibodies [C1q+TPA] and 30/52 patients had no C1q positivity [C1q–DSA].
Death censored graft survival was 94.2% and 87.5% at 1 and 3 years. 14/52 [27%] patients had antibody-mediated rejection [AMR] diagnosed at indication biopsy.
Preformed anti-A, B or DR C1q+DSA strongly predict the occurrence of AMR despite negative crossmatch [all patients with preformed anti-A, B, DR C1q+DSA experienced AMR, p<0.001].
However AMR did not universally occur in patients with Cw, DQ and DP C1q+DSA.
This study confirms our previous findings, using a C4d bead assay, that patients with low level preformed complement fixing DSA are at high immunological risk. The C1qScreen™ assay can identify these patients prospectively and allow intervention to reduce this risk.
Lawrence, C.: Other, OneLambda, Have Received Support To Attend Conferences.
To cite this abstract in AMA style:Lawrence C, Willicombe M, Brookes P, Clarke C, Santos-Nunez E, Roufosse C, Warrens A, Taube D. Complement-Activating Low-Level Preformed Donor-Specific Antibodies Detected by C1qScreen™ Predict Early Antibody-Mediated Rejection in Renal Allografts [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/complement-activating-low-level-preformed-donor-specific-antibodies-detected-by-c1qscreen-predict-early-antibody-mediated-rejection-in-renal-allografts/. Accessed July 30, 2021.
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