Association between donor MBL promoter haplotype and graft survival and the development of BOS after lung transplantation.
BACKGROUND
Lung transplantation is a well accepted therapy for end-stage lung disease, despite high mortality rates. Mortality after transplantation is mainly caused by allograft failure in the first years after transplantation. Mannose binding lectin (MBL), a recognition molecule of innate immunity, has been associated with transplant outcome in other solid organ transplantation. In this study, the effect of donor- and recipient-MBL genotype on lung transplant outcome was investigated.


METHODS
All lung transplantations performed in our center, except from retransplantations and combined lung-liver or heart-lung transplantations, were included. Genotyping of the MBL2 variants (promoter: L/H, Y/X, and P/Q allele and exon 1: A/D, A/B, and A/C allele) was performed in donor and recipient DNA. Analyses on graft survival and the development of bronchiolitis obliterans syndrome were performed with Kaplan-Meier (log rank) survival analysis.


RESULTS
Of the 277 included cases, DNA was available from 189 donors and 200 recipients and genotyping of the promoter single nucleotide polymorphisms was successful in 184 donors and 198 recipients and of the exon 1 single nucleotide polymorphisms in 181 donors and 193 recipients. Patients who received a graft from a donor with an X-allele had better graft survival (P=0.007) and bronchiolitis obliterans syndrome free survival (P=0.007). Recipient MBL genotype was not associated with transplant outcome.


CONCLUSIONS
The donor X-allele, which corresponds to the LXPA haplotype is associated with superior lung transplant outcome. Our findings might prove to be important in finding ways to optimize outcome after lung transplantation.
Munster
Janna M
JM
Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands. j.m.munster@int.umcg.nl
van der Bij
Wim
W
Breukink
Myrte B
MB
van der Steege
Gerrit
G
Zuurman
Mike W
MW
Hepkema
Bouke G
BG
Verschuuren
Erik A M
EA
van Son
Willem J
WJ
Seelen
Marc A J
MA
D000328:Adult; D001989:Bronchiolitis Obliterans / Q000453:epidemiology*; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D008171:Lung Diseases / Q000145:classification / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D037241:Mannose-Binding Lectins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D055815:Young Adult
D037241:Mannose-Binding Lectins; D004247:DNA