Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells
Christof Geisen, Anne North, Lisa Becker, V. Brixner, Melissa von Goetz, Laurence Corash, Richard J. Benjamin, Nina Mufti, Erhard Seifried
Abstract
BACKGROUND: The INTERCEPT™ Blood System for Red Blood Cells (RBCs) utilizes amustaline (S-303) and glutathione (GSH) to inactivate pathogens and leukocytes in transfused RBCs. Treatment-emergent low titer non-hemolytic antibodies to amustaline/GSH RBC were detected in clinical trials using a prior version of the process. The amustaline/GSH process was re-formulated to decrease S-303 RBC adduct formation. STUDY DESIGN AND METHODS: A standard three-cell antibody screening panel was modified to include reagent red cells (RRC) with high (S-303H) or low (S-303L) S-303 adduct density as assessed by flow cytometry, representative of the original and current amustaline/GSH treatment processes, respectively. General hospital and RBC transfusion-dependent patients never exposed, and clinical trial subjects exposed to amustaline/GSH RBC were screened for antibodies to amustaline/GSH RBC using a standardized agglutination assay. RESULTS: isotype) antibodies with acridine (a structural element of amustaline) (n = 14) or non-acridine (n = 3) specificity. 11 of 17 sera reacted with S-303L panel RRCs. In clinical studies 81 thalassemia and 25 cardiac surgery patients were transfused with a total of 1085 amustaline/GSH RBCs and no natural or treatment-emergent S-303 antibodies were detected. CONCLUSION: Standardized RRC screening panels are sensitive for the detection of natural and acquired S-303-specific antibodies. Natural low titer antibodies to amustaline/GSH RBC are present in 0.15% of naïve patients. The clinical relevance of these antibodies appears minimal but is under further investigation.