Aim This case report aimed to evaluate the occurrence of HLA antibodies in non-sensitized patient following immediate allograft loss. Methods Luminex single antigen beads antibodies profile and HLA antigens epitope analysis were used to analyze the HLA antibodies in a 25-year-old female with end-stage renal disease secondary to focal segmental glomerulosclerosis (FSGS). The patient presents for a second renal allograft with a potential living donor. The patient’s first renal allograft was a 0 antigen mismatched organ from her father. The first transplant failed ∼29 months after the transplant due to recurrence of FSGS. The Patient’s typing was: A2, A23, B37, B44, Bw4, Bw4, C2, C5, DRB1 ∗ 11, DRB1 ∗ 15 DQB1 ∗ 06, DQB1 ∗ 03:01 (7). The donor’s typing was: A2, A30, B42, B53, Bw6, Bw4, C4, C17, DRB1 ∗ 13, DRB1 ∗ 18 DQB1 ∗ 04, DQB1 ∗ 03:01 (7). Prior to transplantation the recipient has no IHLA antibodies as determined by solid phase testing and the allogeneic flow cytometry crossmatch was T- and B- cell negative. Twenty-four hours post transplantation the patient undergone transplant nephrectomy for non-immunological causes. Results Strikingly, the post graft-nephrectomy PRA was 98% class I and 0% class II. Antibody specificities were identified to A25, A30 , A31, A34, A66, A68, Bw6 , B13, B27, B38, B49, B51, B52, B53 , B57, B59, B63, B77, C15 antigens (DSAs is highlighted). Immediately after the second graft nephrectomy, the patient became highly sensitized with 98% PRA. Conclusions Short term exposure to allo-antigens under immunosuppression can result in formation of HLA antibodies after allograft nephrectomy and withdrawal of immunosuppressive drugs. High PRA after nephrectomy could be partially attributed to the fact that the patient is homozygous Bw4, and the second donor was positive for the Bw6 public epitope.