T-cell responses to minor histocompatibility antigens (mHAs) mediate both antitumor immunity (graft-versus-leukemia [GVL]) and graft-versus-host disease (GVHD) in allogeneic stem cell transplant. Identifying mHAs with high allele frequency, tight binding affinity to common HLA molecules, and narrow tissue restriction could enhance immunotherapy against leukemia. Genotyping and HLA allele data from 101 HLA-matched donor-recipient pairs (DRPs) were computationally analyzed to predict both class I and class II mHAs likely to induce either GVL or GVHD. Roughly twice as many mHAs were predicted in HLA-matched unrelated donor (MUD) stem cell transplantation (SCT) compared with HLA-matched related transplants, an expected result given greater genetic disparity in MUD SCT. Computational analysis predicted 14 of 18 previously identified mHAs, with 2 minor antigen mismatches not being contained in the patient cohort, 1 missed mHA resulting from a noncanonical translation of the peptide antigen, and 1 case of poor binding prediction. A predicted peptide epitope derived from GRK4, a protein expressed in acute myeloid leukemia and testis, was confirmed by targeted differential ion mobility spectrometry-tandem mass spectrometry. T cells specific to UNC-GRK4-V were identified by tetramer analysis both in DRPs where a minor antigen mismatch was predicted and in DRPs where the donor contained the allele encoding UNC-GRK4-V, suggesting that this antigen could be both an mHA and a cancer-testis antigen. Computational analysis of genomic and transcriptomic data can reliably predict leukemia-associated mHA and can be used to guide targeted mHA discovery.

Introduction Positioning of implant components for total hip arthroplasty (THA) is important for polyethylene liner wear, prosthesis joint stability, and range of motion. The introduction of fluoroscopy for the direct anterior approach has been shown to improve physician accuracy for component positioning. Few studies compare the use of intraoperative fluoroscopy for THA component positioning in posterior THA. The purpose of this project is to retrospectively evaluate the effect of intraoperative fluoroscopy on component positioning for THA using posterior and direct anterior approach (DAA). Materials and Methods A retrospective review of postoperative weight-bearing X-ray films of THAs was performed over a 2-year period where a single fellowship–trained total joint surgeon introduced direct anterior approach into his practice while expanding the intraoperative use of fluoroscopy for all THA procedures, regardless of approach. Component position was evaluated through radiographic measurement of acetabular cup inclination (goal of 40 degrees), limb length discrepancy (goal of 0 mm), and femoral component offset difference (goal of 0 mm). Radiographic analysis was performed by two independent providers. Statistical analysis was performed using Student’s t-tests. Results A total of 107 patients with an average age of 62 years were identified during the 2-year period surrounding the THA practice change, adding fluoroscopy to posterior and DAA THA. Three cohorts were identified: cohort A: 44 patients who underwent posterior THAs without the use of intraoperative fluoroscopy, cohort B: 35 patients who underwent direct anterior approach THAs with the use of intraoperative fluoroscopy, and cohort C: 18 patients who underwent posterior THAs with the use of intraoperative fluoroscopy. The use of intraoperative fluoroscopy for the posterior approach versus unguided posterior approach increased accuracy of both cup inclination (44 degrees vs 50 degrees, P < .05) and femoral offset (4 mm vs 7 mm, P < .05). A comparison of DAA with fluoroscopy versus posterior approach without fluoroscopy showed improvement in cup inclination (48 degrees vs 50 degrees, P < .05). Fluoroscopy with posterior approach versus fluoroscopy with DAA was found to have improved cup inclination (44 degrees vs 48 degrees, P < .05). Conclusion Intraoperative use of fluoroscopy can improve component positioning for posterior THA.

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