Background: Although donor-specific HLA antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor clinical outcome in kidney transplantation, not all DSAs are harmful to graft function. Because complement activation is involved in AMR, distinguishing the complement-fixing is important. The C1q assay on single antigen beads (SAB) is sensitive and specific method to identify complement-fixing HLA antibodies. The aim of this study was to investigate the additional significance of C1q-fixing HLA antibodies for the prediction or diagnosis of rejection over IgG-DSA.

Method: This study included 53 renal transplant patients who had HLA-IgG antibodies by SAB assays. 27 of 53 recipients had biopsy-proven acute or chronic rejection (Rej). We retrospectively tested C1q-fixing HLA antibodies pretransplant and at the time of biopsy using C1q assay.

Results: Of 53 recipients, IgG-DSA class I or class II were detected in 34 (64%) sera, and C1q-fixing HLA antibodies were found in 18 (34.0%) sera. There was no significant difference of IgG-DSA frequencies between Rej(+) and Rej(-) recipients (14(51.9%) vs. 20(76.9%), P=0.106). However, the recipients with rejection had higher frequency of C1q-fixing HLA antibodies than Rej(-) patients (14 (51.9%) vs. 4 (15.4%), P=0.008). In comparison of mean fluorescence intensity (MFI) values on SAB assay with C1q-positivity, high MFI values were associated with C1q-fixation. Sera with high MFI (> 5000) had higher frequency of C1q positivity than sera with low MFI (<5000) (anti-HLA class I, 8/11 (72.7%) vs. 1/21 (4.8%), P<0.001 ; anti-HLA class II, 10/18(55.6%) vs. 1/9 (11.1%), P=0.042, respectively)

Conclusions: Since complement fixing is involved in AMR pathogenesis, a sensitive and specific assay detecting complement-fixing and HLA-specific antibodies would be useful to predict poor clinical outcome in kidney transplant patients.

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