(P-TS-57) HLA Class 1 Antibody Reactivity Is Dynamic Among Patients with Immune-Mediated Platelet Refractoriness: A Retrospective Cohort Study

Background/Case Studies: While a significant body of literature informs our understanding of red blood cell antibody behavior, little has been described about the persistence, evanescence, or senescence of Human Leukocyte Antigen Class 1 antibodies (HLA-1 Ab) in platelet transfusion refractoriness (PTR). This retrospective cohort study describes the observed course of HLA-1 Ab expression over repeat testing of patients with known or suspected immune-mediated PTR towards understanding immune profile dynamicity with implications for clinical transfusion management.

Study

Design/Methods: Patients with two or more episodes of HLA-1 Ab testing performed in the University of California San Francisco health system (UCSF) initiated between 1/1/2021 and 12/31/2023 were included in this study. All HLA-1 Ab test results were recorded, and Calculated Panel Reactive Antibody (cPRA) values were calculated from strong (Mean Fluorescence Intensity, MFI: >8500) and moderate (MFI 2000-8499) HLA-1 Abs, as defined by the UCSF Immunogenetics and Transplantation Laboratory. Patient demographic and clinical data were obtained through electronic medical record review (Epic Systems). This study was approved by the UCSF Institutional Review Board.

Results/Findings: A total of 32 patients met inclusion criteria over the three-year study period. Patients ranged in age from 1 to 76 years (median: 47 years), and 60% were female. Twenty-two patients (69%) were tested three times for HLA-1 Ab, 12 (38%) were tested four times, and 2 (6%) were tested five or more times. The median time between HLA-1 Ab retesting was 53 days. Initial cPRA values ranged from 0% to 100% (median: 64%). Overall, patient cPRA levels varied over time: 21 patients (66%) had cPRA values that decreased from initial to final testing, 8 (25%) had cPRA values that increased, and 3 (9%) had no change in cPRA value. Of the 9 patients with an initial cPRA ≥ 90%, 6 (67%) had a reduction in cPRA over repeat testing, including 3 (33%) whose cPRA ultimately decreased to < 50%.

Conclusions: While not a common practice among peer institutions, at UCSF, where HLA-1 Ab testing is performed in-house, testing may be repeated for clinical (e.g., decreased patient responsiveness to HLA-compatible platelets) or operational (e.g., challenges in obtaining compatible platelets for patients with high cPRA) reasons. The resulting observational dataset of intra-patient HLA-1 Ab reactivity over time reveals dynamicity in cPRA levels, with nearly two thirds of study patients experiencing a decrease cPRA values. These findings challenge the common practice of one-time HLA-1 Ab testing in the management of PTR and may support more nuanced testing strategies, especially for severely HLA-alloimmunized patients. Additional research is ongoing to identify empiric mediators of cPRA dynamicity and inform the appropriate use cases for repeat HLA-1 Ab testing.