PMID- 21152438
OWN - NLM
STAT- MEDLINE
DCOM- 20110208
LR  - 20211020
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 16
DP  - 2010 Nov 11
TI  - Operational post-keratopasty graft tolerance due to differential HLAMatchmaker 
      matching.
PG  - 2362-7
AB  - PURPOSE: Penetrating keratoplasty can restore vision in corneal blindness. 
      However, immunologic rejection threatens graft survival. Matching donors at swine 
      leukocyte antigen (SLA)-class II convey allo-specific tolerance in a large animal 
      kidney-transplantation model despite mismatches at SLA-class I. The same matching 
      pattern seems to account for the blood transfusion effect in kidney 
      transplantation. Relying on the molecular basis of HLAMatchmaker eplets, we 
      assessed whether this finding would also apply to keratoplasty, and if it would 
      enhance the benefit from matching human leukocyte antigen (HLA)-class I alone. 
      METHODS: We retrospectively selected two independent cohorts comprising 586 and 
      975 penetrating keratoplasties. Our computations revealed a quantitative 
      tolerogenicity factor analogous to the animal model. The number of mismatched 
      HLA-class I eplets functioned as a factor for conventional histocompatibility. In 
      the first cohort, we empirically determined the thresholds with the highest 
      predictive power on graft rejection for both factors, and confirmed those 
      thresholds in the second cohort. We applied Cox proportional hazards regression 
      for these analyses. RESULTS: The thresholds with highest predictive power 
      revealed 220 eplets(2) for the tolerance factor and 10 eplets for HLA-class I 
      histocompatibility. The respective hazards ratios were 2.22 (p=0.04) versus 3.63 
      (p<0.01) in the first cohort and 2.09 (p<0.01) versus 1.51 (p=0.02) in the 
      second, confirmatory cohort. The threshold factors proved to be additive in 
      predicting immune reactions in both cohorts, (hazard ratios 2.66 in cohort 1 
      versus 1.70; p<0.01 in cohort 2). CONCLUSIONS: Operational tolerance may be 
      inducible by balanced matching of HLA-class I and II HLAMatchmaker eplets. 
      Furthermore, such tolerance is additive to histocompatibility at HLA-class I.
FAU - Bohringer, Daniel
AU  - Bohringer D
AD  - University Eye Hospital Freiburg, Germany. 
      daniel.boehringer@uniklinik-freiburg.de
FAU - Daub, Frieder
AU  - Daub F
FAU - Schwartzkopff, Johannes
AU  - Schwartzkopff J
FAU - Maier, Philip
AU  - Maier P
FAU - Birnbaum, Florian
AU  - Birnbaum F
FAU - Sundmacher, Rainer
AU  - Sundmacher R
FAU - Reinhard, Thomas
AU  - Reinhard T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101111
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Cohort Studies
MH  - Histocompatibility Antigens Class I/immunology
MH  - Histocompatibility Testing/*methods
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - *Keratoplasty, Penetrating
MH  - Middle Aged
MH  - Proportional Hazards Models
MH  - Reproducibility of Results
MH  - Transplantation Tolerance/*immunology
PMC - PMC2994735
EDAT- 2010/12/15 06:00
MHDA- 2011/02/09 06:00
PMCR- 2010/01/01
CRDT- 2010/12/15 06:00
PHST- 2010/09/21 00:00 [received]
PHST- 2010/11/07 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/02/09 06:00 [medline]
PHST- 2010/01/01 00:00 [pmc-release]
AID - 253 [pii]
AID - 2010MOLVIS0405 [pii]
PST - epublish
SO  - Mol Vis. 2010 Nov 11;16:2362-7.