The Impact of Screening Method on HLA Antibody Detection Before and After Lung Transplantation: A Prospective Pilot Study

Abstract

Introduction: Highly sensitive solid phase assays have allowed for increased identification of human leukocyte antigen (HLA) antibodies pre- and post-lung transplant. However, significant center-to-center variability exists in screening techniques. Some institutions perform an initial screen for the presence of any antibodies and then using single-antigen beads (SAB) to determine antibody identity if the pre-screen is positive. Other institutions do not pre-screen, using SAB only. As a result, there are conflicting data on the epidemiology and relevance of pre- and posttransplant anti-HLA antibodies. Methods: We performed a single center pilot prospective study of adult patients undergoing lung transplantation between July 2015 and October 2016. Enrolled patients had HLA antibody testing prior to transplant and within 3 months post-transplant by 1) pre-screening followed by SAB testing and 2) by SAB alone. Results: Among the 29 enrolled patients, pre-transplant HLA antibodies were found at MFI 1000-3000 in 7 (24.1%) and at MFI >3000 in 2 (6.9%) with the use of pre-screening, and MFI 1000-3000 in 11 (39.3%) patients and at MFI >3000 in 5 patients (17.9%) with SAB alone. The additional pre-transplant antibodies identified by SAB only were not associated with positive retrospective B-cell crossmatch results. Pre-transplant HLA antibody status was more strongly associated with donor-specific HLA antibody development when assessed by pre-screening (OR 9.5, CI 0.8 to 109.2; p 1⁄4 0.07) versus by SAB alone (OR 1.2, 95% CI 0.2 to 5.5; p 1⁄4 0.88). Conclusion: The use of SAB alone is associated with increased identification of HLA antibodies compared to pre-screening followed by SAB. The additional antibodies detected and not associated with positive retrospective B-cell crossmatch or donor-specific HLA antibody formation. This suggests that the additional sensitivity from SAB testing may have limited clinical significance, and its use alone may therefore reduce opportunities for transplant and increase waitlist time.