Recipient HLA-DR3, tumour necrosis factor-alpha promoter allele-2 (tumour necrosis factor-2) and cytomegalovirus infection are interrelated risk factors for chronic rejection of liver grafts.
OBJECTIVE
The tumour necrosis factor (TNF)-2 promoter allele, which elicits elevated expression of TNF-alpha, is in linkage disequilibrium with the extended haplotype HLA-A1-B8-DR3-DQ2. TNF-2 and HLA-DR3 have been implicated in renal and cardiac graft rejection and loss. Cytomegalovirus (CMV) infection has been associated with chronic allograft rejection. We examined the relationship between HLA-DR3, promoter allele TNF-2 and cytomegalovirus in relation to chronic rejection following liver transplantation.


METHODS
(i) Retrospective analysis of HLA-DR3 was performed in 307 liver transplant recipients and 283 donors. (ii) Prospective analysis of TNF-alpha promoter allele status, HLA-DR3 status and cytomegalovirus infection was assessed in 123 recipients.


RESULTS
(i) Retrospective analysis. Recipient HLA-DR3 (relative risk 1.9; 95% C.I. 1.01-3.58) was a risk factor for chronic rejection. (ii) Prospective analysis. Recipient HLA-DR3 was a risk factor for chronic rejection (relative risk 3.41; 95% C.I. 1.66-7.03) which was elevated further by superimposed CMV infection (relative risk 5.01; 95% C.I. 2-12.55). Recipient TNF-2 was associated with chronic rejection (relative risk 2.29; 95% C.I. 0.9-5.83) through linkage to HLA-DR3.


CONCLUSIONS
Recipient HLA-DR3, TNF-2 status and CMV infection were inter-related risk factors for chronic rejection of liver grafts.
Evans
P C
PC
Department of Medicine, University School of Clinical Medicine, Addenbrooke's NHS Trust, Cambridge, UK.
Smith
S
S
Hirschfield
G
G
Rigopoulou
E
E
Wreghitt
T G
TG
Wight
D G
DG
Taylor
C J
CJ
Alexander
G J
GJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000150:complications*; D005260:Female; D008040:Genetic Linkage; D006084:Graft Rejection / Q000209:etiology* / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015803:HLA-DR3 Antigen; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha