Abstract

Transplantation across HLA antibody barriers is associated with an increased risk for early antibody mediated rejection (AMR). Post-transplant monitoring of donor specific HLA-antibody (DSA) is critical to allow for effective anti-rejection intervention. In this HLA incompatible case, we sought to determine whether HLA-C1q data provides additional information regarding the deleterious nature of the DSA or the stage of an immune response (expansion vs. contraction) during an active AMR. HLA-antibodies were assessed in sequential sera using solid phase immunoassays (Lifecodes Single Antigen, Imunor; and C1qScreen, One Lambda). AHG enhanced T cell CDC crossmatch (XM) tests were also performed. On Day +5 post transplant, both HLA-IgG and C1q assays showed a rise in DSA (HLA-A68). Anti-rejection therapy included alternate day plasmapheresis, low dose intravenous Ig (100mg/kg), bortezomib, rituximab, and eculizimab. By Day +9, C1q-MFI for A68 was nearly twofold stronger than the HLA-IgG MFI and the CDC-XM converted from negative to positive. On Day +13, the HLA-IgG MFI remained stable, consistent with a positive CDC-XM, while the HLA-C1q MFI dramatically decreased by tenfold. A negative CDC-XM confirmed the decrease observed on the C1q assay [ Table 1 ]. In this case, HLA-C1q analysis provided additional functional information regarding the quality of the DSA that preceded any change observed on the HLA-IgG immunoassay. This decrease in HLA-C1q may reflect a class switch to a less efficient complement fixing IgG subclass or an affinity change in the dominant clones comprising the DSA antibody repertoire.

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