Multiple Hyperacute Rejections in the Absence of Detectable Complement Activation in a Patient with Endothelial Cell Reactive Antibody

This case involves a 54-year-old patient with polycystic kidney disease and a history of hyperacute allograft rejections. Two previous compatible live donor transplants functioned immediately but failed within the first 12 h due to antibody-injury. This patient was referred for a third transplant due to decreased vascular access and progressive hypotension from uremic autonomic dysfunction. He was broadly sensitized to HLA; however, a live donor was identified through kidney paired donation for whom he had no donor-specific HLA antibody (HLA-DSA). This patient received one plasmapheresis (PP) and intravenous immunoglobulin (IVIg) treatment, anti-CD25, and anti-CD20 antibodies prior to transplant. The allograft functioned immediately but became anuric within 24 h. A biopsy revealed antibody-mediated injury in the absence of C4d. Daily PP/IVIg, a second dose of anti-CD20, and eculizumab were administered. A retrospective endothelial cell crossmatch (ECXM) was positive with serum drawn 3 days prior to transplant and these EC antibodies were enriched for IgG2 and IgG4, noncomplement activating subclasses. Postoperative day (POD) 3, HLA-DSA remained negative but a rescue splenectomy was performed. Cultured splenocytes produced antibodies that bound donor ECs but not lymphocytes. Bortezomib was initiated on POD5. Despite aggressive therapy, the allograft never regained function (read more).

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