PMID- 32888256
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Jan
TI  - Adequate tacrolimus exposure modulates the impact of HLA class II molecular 
      mismatch: a validation study in an American cohort.
PG  - 322-328
LID - 10.1111/ajt.16290 [doi]
AB  - Clinicians have few tools to predict the risk of alloimmune injury that would 
      guide immunosuppression management in renal transplant patients. We evaluated 
      human leukocyte antigen (HLA)-DR/DQ molecular mismatch to predict de novo 
      donor-specific antibodies (DSAs) during the first year of transplant and explored 
      how differences in tacrolimus exposure may modulate this risk. HLA-DR and -DQ 
      eplet mismatches were determined between 444 donor-recipient pairs in Denver, 
      Colorado between 2007 and 2013. Previously defined mismatch thresholds stratified 
      recipients into low- (N = 119), intermediate- (N = 153), and high- (N = 172) risk 
      categories. The area under the curve for DSA at 1 year was 0.84 and 0.82 for 
      HLA-DR and HLA-DQ eplet mismatches, respectively. Compared to low-risk patients, 
      there was a graded increase in risk of DR/DQ DSA in intermediate (HR 15.39, 95% 
      CI 2.01-118.09, p = .009) and high-risk (HR 23.81, 95% CI 3.17-178.66, p = 0.002) 
      categories. Intermediate- and high-risk patients with a mean tacrolimus <6 ng/ml 
      versus >8 ng/ml had increased risk of DR/DQ DSA at 1 year (HR 2.34, 95% CI 
      1.05-5.22, p = .04). HLA molecular mismatch represents a reproducible, objective, 
      and clinically relevant tool to stratify patients by alloimmune risk and may help 
      guide personalized immunosuppression management.
CI  - (c) 2020 The Authors. American Journal of Transplantation published by Wiley 
      Periodicals LLC on behalf of The American Society of Transplantation and the 
      American Society of Transplant Surgeons.
FAU - Davis, Scott
AU  - Davis S
AUID- ORCID: 0000-0001-5320-4435
AD  - Department of Medicine, University of Colorado, Aurora, Colorado, USA.
FAU - Wiebe, Christopher
AU  - Wiebe C
AUID- ORCID: 0000-0002-1006-3545
AD  - Department of Medicine, Rady Faculty of Health Sciences, Winnipeg, Manitoba, USA.
FAU - Campbell, Kristen
AU  - Campbell K
AD  - Department of Medicine, University of Colorado, Aurora, Colorado, USA.
FAU - Anobile, Cheri
AU  - Anobile C
AD  - ClinImmune Labs, Aurora, Colorado, USA.
FAU - Aubrey, Michael
AU  - Aubrey M
AD  - ClinImmune Labs, Aurora, Colorado, USA.
FAU - Stites, Erik
AU  - Stites E
AD  - Department of Medicine, University of Colorado, Aurora, Colorado, USA.
FAU - Grafals, Monica
AU  - Grafals M
AD  - Department of Medicine, University of Colorado, Aurora, Colorado, USA.
FAU - Pomfret, Elizabeth
AU  - Pomfret E
AD  - Department of Surgery, University of Colorado, Aurora, Colorado, USA.
FAU - Nickerson, Peter
AU  - Nickerson P
AUID- ORCID: 0000-0002-7393-7799
AD  - Department of Medicine, Rady Faculty of Health Sciences, Winnipeg, Manitoba, USA.
FAU - Cooper, James E
AU  - Cooper JE
AD  - Department of Medicine, University of Colorado, Aurora, Colorado, USA.
LA  - eng
PT  - Journal Article
DEP - 20201011
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 (HLA-DR Antigens)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
CIN - Am J Transplant. 2021 Jan;21(1):9-10. PMID: 33107168
MH  - *Graft Rejection/etiology
MH  - Graft Survival
MH  - HLA Antigens/genetics
MH  - HLA-DR Antigens
MH  - Histocompatibility Testing
MH  - Humans
MH  - *Tacrolimus
MH  - United States
PMC - PMC7821185
OTO - NOTNLM
OT  - alloantibody
OT  - autoimmunity
OT  - clinical research / practice
OT  - histocompatibility
OT  - immunosuppressant - calcineurin inhibitor: tacrolimus
OT  - immunosuppression / immune modulation
OT  - kidney transplantation / nephrology
OT  - monitoring: immune
OT  - rejection
COIS- The authors of this manuscript have no conflicts of interest to disclose as 
      described by the American Journal of Transplantation.
EDAT- 2020/09/06 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/01/22
CRDT- 2020/09/05 05:21
PHST- 2020/05/13 00:00 [received]
PHST- 2020/08/07 00:00 [revised]
PHST- 2020/08/24 00:00 [accepted]
PHST- 2020/09/06 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/09/05 05:21 [entrez]
PHST- 2021/01/22 00:00 [pmc-release]
AID - S1600-6135(22)08342-3 [pii]
AID - AJT16290 [pii]
AID - 10.1111/ajt.16290 [doi]
PST - ppublish
SO  - Am J Transplant. 2021 Jan;21(1):322-328. doi: 10.1111/ajt.16290. Epub 2020 Oct 
      11.