PMID- 33078553
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 21
IP  - 3
DP  - 2021 Mar
TI  - Estimating alloantibody levels in highly sensitized renal allograft candidates: 
      Using serial dilutions to demonstrate a treatment effect in clinical trials.
PG  - 1278-1284
LID - 10.1111/ajt.16363 [doi]
AB  - Small reductions in calculated panel-reactive antibody (cPRA) are associated with 
      increased kidney transplantation in 100% cPRA patients. However, the high level 
      of antibody in these patients is such that desensitization may reduce antibody 
      but not cPRA, thus the cPRA change on undiluted serum with desensitization is an 
      insensitive measure of effectiveness. We evaluated cPRA reduction, calculated per 
      antibody titer, as a desensitization trial endpoint. To accomplish this, two 
      serum samples from 20 kidney transplant candidates with cPRA >/=99.9% (100%) were 
      obtained and serially diluted in triplicate to determine the titer of individual 
      human leukocyte antigen (HLA) antibody specificities. CPRA was computed per 
      dilution to identify the titer at which cPRA drops below 98%. Inter- and 
      intra-assay variability and changes overtime were determined. The dilution needed 
      to reach a cPRA <98% was within 1 titer for replicates from the same sample, with 
      90% (36/40) concordance. This indicates that only changes >2 titers can be deemed 
      clinically meaningful. The median (IQR) titer difference was 0 (0-1) from 
      baseline to follow-up within 12 months. The cPRA per titer also risk-stratified 
      candidates for trial inclusion. In conclusion, determining the cPRA per titer is 
      a reliable approach to simplify complex antibody data and an ideal endpoint for 
      desensitization trials.
CI  - (c) 2020 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Tambur, Anat R
AU  - Tambur AR
AUID- ORCID: 0000-0002-0320-9825
AD  - Northwestern University, Chicago, Illinois, USA.
FAU - Schinstock, Carrie
AU  - Schinstock C
AUID- ORCID: 0000-0002-3274-3277
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Maguire, Chelsea
AU  - Maguire C
AD  - Northwestern University, Chicago, Illinois, USA.
FAU - Lowe, David
AU  - Lowe D
AD  - One Lambda, Los Angeles, California, USA.
FAU - Smith, Byron
AU  - Smith B
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Stegall, Mark
AU  - Stegall M
AUID- ORCID: 0000-0002-1392-0792
AD  - Mayo Clinic, Rochester, Minnesota, USA.
LA  - eng
PT  - Journal Article
DEP - 20201211
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (HLA Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - Allografts
MH  - HLA Antigens
MH  - Histocompatibility Testing
MH  - Humans
MH  - Isoantibodies
MH  - *Kidney Transplantation
OTO - NOTNLM
OT  - alloantibody
OT  - clinical research / practice
OT  - desensitization
OT  - histocompatibility
OT  - kidney transplantation / nephrology
OT  - panel reactive antibody (PRA)
OT  - sensitization
EDAT- 2020/10/21 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/10/20 06:29
PHST- 2020/07/12 00:00 [received]
PHST- 2020/09/30 00:00 [revised]
PHST- 2020/10/05 00:00 [accepted]
PHST- 2020/10/21 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/10/20 06:29 [entrez]
AID - S1600-6135(22)08462-3 [pii]
AID - 10.1111/ajt.16363 [doi]
PST - ppublish
SO  - Am J Transplant. 2021 Mar;21(3):1278-1284. doi: 10.1111/ajt.16363. Epub 2020 Dec 
      11.