Changes in successive measures of de novo donor-specific anti-human leukocyte antigen antibodies intensity and the development of allograft dysfunction.

Abstract

Many patients develop de novo donor-specific anti-human leukocyte antigen antibodies (dnDSA) after transplantation. Despite development of dnDSA, not all patients will immediately fail. This study analyzes dnDSA intensity and longitudinal trends as prospective clinical parameters to assess subsequent allograft function. Twenty-four patients with dnDSA onset in the first 2 years after transplantation received antibody monitoring by LABScreen single antigen beads. Estimated glomerular filtration rate (eGFR) was recorded at time of dnDSA onset and up to 24 months thereafter. The dnDSA mean fluorescence intensity (MFI) of the stable function patient group (n=8; eGFR decline ≤ 25%) was compared with the impaired function patient group (n=16; eGFR decline>25%) using first year peak MFI (pMFI), eight month MFI change (ΔMFI), and eighteen month MFI trend (MFI slope). Both groups showed similar dnDSA characteristics (time to onset after transplantation, class I/II distribution, and initial MFI). Between groups, MFI trends were analyzed. Impaired patients showed a higher pMFI during the first year (median pMFI, 13,055 vs. 2,397; P=0.007). Longitudinal analysis revealed that ΔMFI was strongly associated with dysfunction. Both a ΔMFI increase greater than 20% as well as a stronger increase (ΔMFI>50%) were followed by graft dysfunction in almost all patients and could significantly differentiate between stable and impaired function patients (P=0.001 and P=0.04, respectively). Our study suggests that tracking dnDSA intensity, particularly in the early period after onset, is important to estimate the impact of dnDSA on the allograft and could, therefore, determine help on how best to monitor patients with dnDSA.