Post-transplantation dynamics of non-HLA antibodies and early panel intensity as predictors of ABMR in kidney transplantation
Jinghong Tan1, Mingchuan Huang1, Wenrui Wu1, Huanxi Zhang1, Longshan Liu1, Changxi Wang1.
1Organ Transplant Center, the First Affliated hospital of Sun Yet-sen University, Guangzhou, People's Republic of China
Purpose: The potential role of non-human leukocyte antigen (non-HLA) antibodies in kidney allograft antibody-mediated rejection (ABMR) has been proposed. The post-transplant evolution and association of antibodies with ABMR development remains unclear.
Methods: In a single-center retrospective study, we examined the ABMR group (n = 15) and the stable allograft function group (n = 15). Serum samples collected pre-transplantation and at post-transplantation days 7, 30, 90, 180, and 360 underwent testing for a panel of 60 non-HLA antibodies. Antibody intensity was calculated by comparing measured MFI values with kit cutoff MFI values. Spearman correlation was to evaluate correlation among antibodies. Regression models were to evaluate the predictive capacity of non-HLA antibodies on ABMR.
Results: Total non-HLA antibody intensity was comparable between the two groups pre-transplantation. Antibody intensity decreased at day 7 post-transplantation, returning to pre-transplantation levels around day 30, followed by a gradual increase in intensity in both groups. Eight out of the 60 non-HLA antibodies demonstrated significantly higher intensity in ABMR recipients and predictive capacity for ABMR at day 30. After excluding highly correlated antibodies, KRT8, PECR, and PLA2R1 antibodies were included for the panel. The panel antibody intensity was significantly higher in ABMR recipients both pre-transplantation and at day 30 post-transplantation. Recipients with high antibody intensity at day 30 had a significantly elevated risk of ABMR incidence compared to those with lower intensity (One-year: 50% (29.6% - 84.4%) vs 86.7% (71.1% - 100%), p = 0.002). Both intensity and intensity-based grade were independently associated with a higher risk of ABMR (Intensity: HR = 2.30, CI 1.32 - 4.01, p = 0.003; Grade: HR = 4.59, CI 1.23 - 17.21, p = 0.024).
Conclusions: Non-HLA antibody intensity exhibited a decline and subsequent rebound shortly after transplantation. A high antibody intensity panel, including KRT8, PECR, and PLA2R1 antibodies at day 30 post-transplantation, demonstrated predictive capacity for ABMR.
