Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

Abstract

Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immuno histochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome. Key words: Acute humoral rejection, B-cell-mediated rejection, CD20-mediated rejection, Renal transplantation, Rituximab IntroductionTransplant remains the optimal treatment for patients with end-stage renal disease. 1 Acute graft rejection remains a common complication and affects long-term graft survival. 2,3 Advances in immunosuppressive protocols have led to improvements in acute graft rejection episodes. 3-6 However, acute graft rejection, especially antibody-mediated rejection (AMR), can cause graft loss in some patients and can shorten graft function time in others. The presence of CD20-positive cells in the graft has been associated with poor reversibility of graft function and a trend toward poor graft survival even without AMR. 7-9 Anti-CD20 antibodies (rituximab) have been used as rescue therapy for CD20-mediated refractory acute rejection with successful outcomes. 7,10-15 Herein, we report a case of refractory acute cellular rejection with clusters of CD20-positive lymphocyte graft infiltrates, resistant to steroid pulses, plasmapheresis, and switching of immunosuppressive drug regimen, which was successfully treated with anti-CD20 antibodies. Case ReportA 39-year-old-male with type 2 insulin-dependent diabetes presented with end-stage kidney disease and with both kidneys having small size. The patient had been on regular hemodialysis for 3 years.The patient received a right iliac renal allograft from his 27-year-old brother. The sibling donor had a different compatible blood group, one mismatched HLA DR, negative repeated complement-dependent crossmatch test, and 7% donor nonspecific panel reactive antibody (PRA) class I and 0% PRA class II. There were no complications during the transplant procedure and postoperative period, with total ischemia time of 55 minutes and immediate diuresis. Induction immunosuppr...