Paper 42: Effects of Blood Type Mismatching on Functional Graft Survival after Osteochondral Allograft Transplantation. Issue 7 (30th July 2022) - Williams, Jonathan
Objectives: To explore a factor that may contribute to potentially detrimental sub-rejection immune responses, we compared donor and recipient blood types following osteochondral allograft (OCA) transplants from a subset of patients in an IRB-approved dedicated lifelong registry to determine potential relationships for blood type mismatches with documented graft failures. The study was designed to test the hypothesis that OCA transplantation patients receiving blood type mismatched allografts would be more likely to require OCA revision or artificial arthroplasty surgery compared to those receiving donor-recipient matched allografts. Methods: A subset of patients was selected from those enrolled (n=414) in our center's IRB-approved lifelong registry for OCA transplantation clinical outcomes. This subset included patients with complete donor and recipient ABO and Rh Factor data available such that there was a 2:1 ratio of successful versus failed outcomes for age-, BMI-, and joint-matched OCA transplant recipients for statistical analyses. Donor blood type information was obtained from the respective tissue banks. Recipient blood type information was obtained from electronic medical records. Patients who required OCA revision or artificial arthroplasty were defined as graft failures. Outcomes were assessed for all patients included in the blood type mismatching analyses. Osteochondral tissues that were resected from the knee, hip, and ankle of patients undergoing standard-of-care revision or arthroplasty surgeries, and that otherwise would be discarded, were recovered for histologic assessments. Subjective histologic assessments were performed by a pathologist who was blinded to patient demographics, blood typing information, outcomes data, and tissue source. When aggregates of lymphocytes and plasma cells were observed surrounding small blood vessels (consistent with an immune response), immunohistochemistry for CD3, CD8, and CD20 was performed to further characterize the lymphocytes (T cell marker, cytotoxic T lymphocytes, and B cell marker, respectively) for subjective assessment of relevant immune responses. Subjects were grouped by ABO blood type, Rh Factor, and both. Histologically evaluated failures were separated by immune response as positive or negative. Fisher's exact tests were used for statistical analyses with a p-value of less than 0.05 set a priori to define statistical significance. Results: A total of 103 patients were included for analysis with 33 of these requiring OCA revision or artificial arthroplasty. Of the clinical failures, 18 had previously transplanted osteochondral allograft tissues recovered for histological assessment. Twelve (66%) of these recovered OCAs had aggregates of CD3+, CD8+, and CD20+ lymphocytes around small blood vessels in the bone marrow spaces and adipose/collagenous tissue of the previously transplanted allograft. The remaining resected OCAs (34%) did not show a similar pattern of T- and B-cell infiltrates around blood vessels. Other histologic abnormalities associated with failed OCAs included avascular necrosis, subchondral micro and macro fractures, subchondral collapse, and/or articular cartilage erosion or delamination. No statistically significant differences in proportions for success versus failure based on mismatches for ABO type, Rh Factor, or both were noted. Similarly, no statistically significant differences in proportions for positive versus negative immune responses based on mismatches for ABO type, Rh Factor, or both were noted. Conclusions: Donor-recipient mismatches for ABO blood type and/or Rh Factor were not associated with higher likelihood for patients to require OCA revision or artificial arthroplasty surgery. Similarly, donor-recipient mismatches for ABO blood type and/or Rh Factor were not associated with higher likelihood for positive immune responses in previously implanted OCA tissues recovered from patients who required revision or artificial arthroplasty surgeries. However, two-thirds of the tissues recovered from graft failure cases had T- and B-cell infiltrates, suggesting sub-rejection immune responses occur after OCA transplantation that should be further investigated to determine potential mechanistic relationships with graft failures. The results of the present study support current clinical practice for transplantation of fresh OCAs, which does not require HLA or blood type matching or immunosuppressive medication for recipients. However, histologic assessments suggest that sub-rejection immune responses may play a role in graft failures and should be further investigated.