Late Antibody-Mediated Rejection in a Large Prospective Cross-Sectional Study of Kidney Allograft Recipients--Preliminary Results of the Screening Phase of the BORTEJECT Trial.
There is limited data on the rate of late antibody-mediated rejection (ABMR) in unselected transplant cohorts. Here, we investigated the prevalence and characteristics of ABMR in a large cohort of long-term kidney allograft recipients. Patients were screened in the context of a randomized controlled trial (BORTEJECT study; ClinicalTrials.gov: NCT01873157) designed to investigate the impact of bortezomib on the course of late ABMR. The study (initiation in October 2013) includes a cross-sectional ABMR screening (key inclusion criterion: functioning graft at ≥ 180 days) to identify 44 recipients eligible for inclusion in the intervention trial. Patients were screened for donor-specific antibodies (DSA) applying solid phase technology and DSA+ recipients underwent protocol biopsies. Through November 2014, ABMR screening (after a median of 6.5 years post-transplantation) had been completed for 714 recipients. One hundred one patients (14%) had DSA above a threshold of 1,000 mean fluorescence intensity (MFI). Forty-four of 78 DSA+ recipients (6% of the overall cohort) subjected to biopsy were diagnosed with C4d-positive (n = 17) or -negative (n = 27) ABMR and 40 consented to participate in the intervention trial. DSA+ABMR+ and DSA+ABMR- patients differed significantly with respect to the MFI of the highest level DSA (P < 0.001), whereby ABMR or C4d positivity were moderately predicted by MFI values (area under the receiver operating characteristic curve: 0.75 and 0.84, respectively). In conclusion, the results of this cross-sectional analysis suggest a ≥ 6% prevalence of late ABMR. We demonstrate that the more frequent finding of circulating DSA may not necessarily associate with ABMR diagnosis, especially in patients with low antibody levels.
Farsad
F
Eskandary
Gregor
G
Bond
Heinz
H
Regele
Nicolas
N
Kozakowski
Zeljko
Z
Kikić
Markus
M
Wahrmann
Helmuth
H
Haslacher
Rainer
R
Oberbauer
Vido
V
Ramassar
Philip
P
Halloran
Georg A
GA
Böhmig
D000368:Aged; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage; D012307:Risk Factors; D012698:Serologic Tests; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011719:Pyrazines; D000069286:Bortezomib