Long-term outcome of lung transplantation is predicted by the number of HLA-DR mismatches.
BACKGROUND
The importance of HLA mismatch in determining long-term outcome in lung transplantation remains largely uncertain.


METHODS
A retrospective analysis of 102 consecutive primary lung transplants was performed to identify risk factors for poor long-term outcome after lung transplantation defined as graft survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables included were patient characteristics (age, sex, prior diagnosis), the number of HLA mismatches between donor and recipient, cold ischemic time, cytomegalovirus serologic concordance, number of acute rejections, and time to first rejection. Variables carrying significance in a univariate analysis were subjected to a proportional hazard regression analysis.


RESULTS
In the multivariate analysis, an increased number of acute rejections correlated positively with decreased graft survival (risk ratio [RR] = 1.25; 95% confidence interval [CI], 1.05-1.5; P = 0.011), development of BOS stage I (RR = 1.36/episode; 95% CI, 1.16-1.58;P < 0.001), and BOS stage II (RR = 1.42/episode; 95% CI, 1.2-1.67; P < 0.001). An increased time to rejection correlated positively with reduced graft survival (RR = 1.03/day; 95% CI, 1.01-1.06; P = 0.02), and BOS stage I and II (both RR = 1.04/day; 95% CI, 1.01-1.07; P < 0.005). Compared with 2 HLA-DR mismatches, 0 or 1 mismatch was associated with improved graft survival (RR = 0.43; 95% CI, 0.19-0.98; P = 0.045) and protected against development of BOS stage I (RR = 0.47; 95% CI, 0.23-0.98; P = 0.044) and BOS stage II (RR = 0.35; 95% CI, 0.15-0.83; P = 0.017).


CONCLUSIONS
HLA-DR mismatching appears to be a risk factor for the development of BOS and graft loss. Improved outcome after lung transplantation might be achieved with prospective matching for HLA-DR. Alternatively, the amount and type of immunosuppressive drugs may be guided by the degree of HLA-DR (mis)matching.
Department of Pulmonary Diseases, University Hospital Groningen, The Netherlands. j.w.k.van.den.berg@isala.nl
J W
JW
van den Berg
B G
BG
Hepkema
A
A
Geertsma
G H
GH
Koëter
D S
DS
Postma
W J
WJ
de Boer
S P
SP
Lems
W
W
van der Bij
D000293:Adolescent; D000328:Adult; D001989:Bronchiolitis Obliterans / Q000209:etiology; D002648:Child; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006684:HLA-DR Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D013997:Time Factors; D016896:Treatment Outcome
D006684:HLA-DR Antigens