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Two index cases of living-related donor renal allografts patients developed C4d-negative rejection. Both cases had negative cytotoxic crossmatch and negative flow crossmatch before transplantation. The serum creatinine levels were tabulated. Both cases experienced augmented anti-T cell therapy (intravenous methyl prednisolone) at the time of rejection, which failed to improve renal function. Meantime, our HLA lab identified circulating anti-class I and/or II HLA antibodies towards donor mismatched antigens by Luminex multiplex bead array. Additional therapy included high-dose IVIg and plasma exchange. The renal function improved significantly. Furthermore, the donor-specific antibody strength decreased after combined plasmapheresis and IVIG therapy. These cases highlight the importance of donor-specific antibody detection by sensitive solid phase assays in the context of C4d-negative ABMR.

The importance of donor-specific anti-HLA antibodies (DSA) identification in renal transplant patients with C4d-negative biopsies