PMID- 12803340
OWN - NLM
STAT- MEDLINE
DCOM- 20030926
LR  - 20061115
IS  - 0966-8519 (Print)
IS  - 0966-8519 (Linking)
VI  - 12
IP  - 3
DP  - 2003 May
TI  - Aortic valve allograft structural deterioration is associated with a subset of 
      antibodies to human leukocyte antigens.
PG  - 382-90; discussion 390-1
AB  - BACKGROUND AND AIM OF THE STUDY: The association between aortic valve allograft 
      dysfunction in patients with long-term follow up and human leukocyte class 2 
      antigen donor/recipient mismatch suggests that elements of the anti-donor immune 
      response penetrate and damage the aortic valve allograft. An aortic valve 
      allograft recipient cohort was studied to determine whether presence of recipient 
      antibodies to donor human leukocyte class 1 or 2 antigen was associated with 
      shorter time to aortic valve allograft dysfunction. METHODS: Both donor and 
      recipient human leukocyte antigen (HLA) type, HLA antibody information and 
      echocardiography data were available for 148 recipients of cryopreserved aortic 
      valve allografts between 1986 and 1998. Structural deterioration of the aortic 
      valve allograft was defined as at least moderate aortic stenosis or regurgitation 
      by echocardiography. Recipient sera were assayed for anti-HLA (class 1 and 2) 
      antibodies using three assays: complement-dependent cytotoxicity (CDC) on T- and 
      B-lymphocyte panels (CDC PRA); flow cytometry using HLA-coated beads (Flow PRA); 
      and an ELISA using HLA-coated microwells. The donor specificity of anti-class 1 
      and 2 HLA antibodies was determined on T- and B-cell panels using CDC. 
      Associations between the results of the three assays and donor-specific class 1 
      and 2 antibodies and time to structural deterioration were analyzed using 
      Kaplan-Meier curves of freedom from structural deterioration. Cox 
      proportional-hazards were used to determine independent predictors of time to 
      structural deterioration. RESULTS: Patients highly positive for HLA class 2 
      antibodies using an ELISA had a significant association (p = 0.007) with shorter 
      time to aortic valve allograft structural deterioration using both a log rank 
      test and Cox proportional-hazards analysis. Patients (n = 15) with donor-specific 
      antibodies to class 2 antigen (DR antigens) had significantly more structural 
      deterioration (p = 0.035) than those without specific antibodies. CONCLUSION: The 
      association between aortic valve allograft structural deterioration and high 
      titer human leukocyte class 2 antigen antibodies, a subset detected by ELISA adds 
      further information about the link between HLA class 2 mismatch and structural 
      deterioration. Further studies are needed to confirm the importance of class 2 
      antibodies on outcome, and to determine by which method these antibodies should 
      be detected. Potential recipients with pre-existing antibodies of these specific 
      types might be expected to sustain accelerated allograft damage.
FAU - Dignan, Rebecca
AU  - Dignan R
AD  - Department of Cardiothoracic Surgery and Clinical Research Center, Vanderbilt 
      University, Nashville, TN, USA.
FAU - O'Brien, Mark
AU  - O'Brien M
FAU - Hogan, Patrick
AU  - Hogan P
FAU - Thornton, Alycia
AU  - Thornton A
FAU - Fowler, Kirsten
AU  - Fowler K
FAU - Byrne, Daniel
AU  - Byrne D
FAU - Stephens, Fiona
AU  - Stephens F
FAU - Harrocks, Susan
AU  - Harrocks S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Heart Valve Dis
JT  - The Journal of heart valve disease
JID - 9312096
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Aortic Valve/immunology/*transplantation
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Cryopreservation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/*immunology
MH  - Graft Survival
MH  - HLA Antigens/analysis
MH  - HLA-DR Antigens/analysis
MH  - Heart Valve Diseases/*surgery
MH  - Histocompatibility Antigens Class II/analysis/*immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Probability
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Risk Assessment
MH  - Tissue Donors
MH  - *Transplantation Immunology
MH  - Transplantation, Homologous
EDAT- 2003/06/14 05:00
MHDA- 2003/09/27 05:00
CRDT- 2003/06/14 05:00
PHST- 2003/06/14 05:00 [pubmed]
PHST- 2003/09/27 05:00 [medline]
PHST- 2003/06/14 05:00 [entrez]
PST - ppublish
SO  - J Heart Valve Dis. 2003 May;12(3):382-90; discussion 390-1.