Incidence and prediction of early antibody-mediated rejection due to non-human leukocyte antigen-antibodies.
BACKGROUND
Antibody-mediated rejection (AMR) is responsible for a large proportion of early allograft losses. While preformed donor-specific human leukocyte antigen (HLA)-antibodies (HLA-DSA) are accountable for the majority of these episodes, non-HLA-DSA are also involved. However, data on the incidence of early AMR due to non-HLA-DSA are currently lacking.


METHODS
This study evaluated (i) the incidence of early AMR due to non-HLA-DSA -- defined by exclusion of circulating HLA-DSA detected by flow beads -- and (ii) the association with donor-specific major histocompatibility complex class I chain-related gene (MICA)-antibodies (MICA-DSA) and angiotensin-receptor antibodies. A retrospective cohort (n=279) risk stratified by complement-dependent cytotoxicity crossmatches (CDC-XM era) and a prospective cohort (n=154) risk stratified by virtual crossmatching using flow beads (virtual-XM era) were investigated.


RESULTS
In the CDC-XM era 25/279 patients (9%) developed early AMR, but only 3/154 patients (2%) in the virtual-XM era (P=0.004). The incidence of early AMR due to HLA-DSA was significantly higher in the CDC-XM era than in virtual-XM era (18/279 patients [6.5%] vs. 0/154 patients [0%]; P=0.0005). However, the incidence of early AMR presumably due to non-HLA-DSA remained unchanged in these two cohorts (7/279 patients [2.5%] vs. 3/154 patients [2%]; P=1.0) consistent with a persisting gap in the ability to identify preformed DSA. Overall, 10/433 patients (2.3%) experienced early AMR presumably due to non-HLA-DSA. None of these 10 patients had angiotensin-receptor antibodies, at most 3/10 patients had MICA-DSA, while the antibodies remained unexplained in 7/10 cases.


CONCLUSIONS
Early AMR due to non-HLA-DSA is a rare event, which is still difficult to predict by currently available assays.
Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Patrizia
P
Amico
Gideon
G
Hönger
Denise
D
Bielmann
Doris
D
Lutz
Daniela
D
Garzoni
Jürg
J
Steiger
Michael J
MJ
Mihatsch
Duska
D
Dragun
Stefan
S
Schaub
D000906:Antibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D000906:Antibodies; D006683:HLA-DQ Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D044140:Receptor, Angiotensin, Type 1