*Purpose: Human leukocyte antigen-identical renal transplants among siblings account for a minority of all renal transplants, but have excellent long-term outcomes due to very minimal or no rejection. Rule of thumb is often to titrate down immuno-suppression in such recipients, including use of steroid free protocols.We describe two cases of HLA identical sibling transplants with severe acute rejection, and use of mixed lymphocyte culture for T-cell reactivity

*Methods: A 46-year-old female with history of IgA Nephropathy resulting in ESRD, underwent a live donor kidney transplant from her HLA identical brother. Her pre-transplant calculated panel reactive antibodies (cPRA) were 0%. She received basiliximab/methylprednisolone induction following which she was transitioned to mycophenolate, tacrolimus and prednisone. Prednisone was withdrawn at one week post-transplant and continued on a steroid free protocol. She maintained good allograft function until 30 months post-transplant when serum creatinine was elevated 2.27 from her baseline of 1.1. She had therapeutic tacrolimus levels, normal urine sediment, no proteinuria, negative CMV/ BKV PCR in serum, and a normal allograft ultrasound. Allograft biopsy was consistent with Banff type 1B acute cellular rejection. C4d was negative in peritubular capillaries. We performed Immuno-histochemical staining with CD3/ CD68 antibodies on the tissue which confirmed the infiltrating cells to be lymphocytes. We employed mixed lymphocyte culture (MLC) tests which have historically been used to assess antigenic similarity between donor and recipient. The inability of lymphocytes mixed in culture to proliferate correlates with antigenic similarity, but T cell proliferation demonstrated on flow cytometry indicates the contrary. Interestingly, our recipient displayed T cell reactivity towards the donor cells on MLC, which was markedly higher compared to lymphocytes from three non-matched HLA controls.

*Results: We had another sibling pair with HLA-identical living donor transplant with severe acute cellular rejection 5 years after the transplantation. However, this recipient had non-compliance to immunosuppression for a prolonged period.

*Conclusions: These cases emphasize that severe acute rejections can occur in HLA identical kidney transplants. The age-old method of mixed lymphocyte reaction confirms T cell reactivity that is most likely causing these rejections. The exact antigenic stimulus for these rejections is ill-understood and needs further research.

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