Heterogeneity of Non-HLA Antibody Prevalence in Kidney Antibody-mediated Rejection With the Commercial Luminex Assays

The current state of non-HLA antibody testing in antibody-mediated rejection (AMR) remains not standardized and controversial.

We used 2 different commercial solid-phase assays to investigate the presence of non-HLA antibodies in a cohort of kidney transplant recipients stratified according to biopsy-proven AMR and HLA-donor-specific antibody status.

Assay 1 and 2 evaluated 60 and 39 different non-HLAs, of which 25 were shared. From the 25 common antigens, only 36% (n = 9) have a moderate correlation ( r ≥ 0.6) in signal intensity. We observed significant heterogeneity in the prevalence of specific non-HLA antibodies detected between assay 1 and 2. Furthermore, the 2 assays showed substantial differences in the quantities, as well as specificities, of the positive non-HLA antibodies in each patient. Overall, the number of patients with positive antibodies that were detected by both assays was relatively low (median, 5 patients [interquartile range, 3-8] and 6 patients [interquartile range, 3-10] for transplant and biopsy samples, respectively, according to different antigens). Additionally, the panel of specific non-HLA antibodies found associated with AMR (and specifically with AMR/HLA donor-specific antibody negative) and graft loss was assay dependent.

We have shown that the current non-HLA antibody assays exhibit significant heterogeneity in terms of antibodies identified per patient and in association with rejection and graft loss.