Pretransplant C1q Fixing Human Leukocyte Antigen Antibodies and Humoral Rejections in Patients after Living Kidney Transplantation

Antibodies (Abs) directed against human leukocyte antigens (HLA) are associated with antibody mediated rejection and graft failure after kidney transplantation, but the problem of discrimination between relevant and irrelevant HLA Abs detected by solid phase assays has still not been solved. The new C1q assay based on single antigen beads detects a subset of HLA Abs that is able to fix the complement component C1. In this preliminary study we retrospectively analyzed C1q fixing HLA Abs in 20 selected living kidney transplantation donor/recipient pairs. Group A comprised 9 recipients with biopsy proven acute rejection. Six of them had positive pretransplant flow cytometric T cell crossmatches (FCXM). Group B comprised 11 recipients with negative FCXM results and without rejection. We measured pretransplant IgG HLA Abs using single antigen beads and subsequently also C1q fixing HLA Abs. Pretransplant testing of group A revealed 7 (78%) HLA-class I positive patients [3 (43%) with donor-specific Abs (DSA)] and 6 (67%) HLA-class II positive patients [2 (33%) with DSA]. Testing of group B resulted in comparable results: 8 (72%) HLA-class I positive patients [2 (25%) with DSA], and 7 (64%) HLA-class II positive patients [1 (14%) with DSA], respectively. Subsequent analysis of C1q fixing Abs within group A confirmed two patients to be positive for HLA-class I Abs, and only one for HLA-class II. DSA was not detected in any patient of group A. Group B was completely negative. Therefore, a trend to a higher risk for humoral rejections could be observed when pretransplant C1q positivity was present (p=0.07, RR 2.83, OR 12.38). Two of the three C1q positive patients were also positive for pretransplant cytotoxic antibodies, which supports the validity of the C1q assay. Our study indicates a potential improvement of HLA antibody analysis with single antigen beads using the C1q assay. A multicenter study has been initiated to confirm our preliminary results.