Polymorphisms in innate immunity genes associated with development of bronchiolitis obliterans after lung transplantation.
BACKGROUND
Activation of the immune system is suggested to prevent transplant tolerance and to promote the development of bronchiolitis obliterans syndrome (BOS). The innate immune system is activated by the interaction of pathogen-associated molecular patterns of microorganisms with Toll-like receptors (TLRs). Activation of innate immunity via TLRs was shown to be a barrier to the induction of transplantation tolerance after lung transplantation. We hypothesized that polymorphisms in 10 genes coding for TLR1 to TLR10 might contribute to an altered immune response and the subsequent development of BOS.


METHODS
DNA was collected from 110 lung transplant recipients. Twenty patients developed BOS. The control group comprised 422 individuals. Sixty-four single-nucleotide polymorphisms (SNPs) in 10 genes coding for TLR1 to TLR10 were genotyped.


RESULTS
The genotype distribution of TLR2 (rs1898830 and rs7656411), TLR4 (rs1927911) and TLR9 (rs352162 and rs187084) was significantly different between BOS(pos) patients and BOS(neg) patients and controls. The BOS(pos) group had significantly more patients with 3 or 4 of these risk alleles compared with the BOS(neg) and control groups.


CONCLUSIONS
Polymorphisms in TLR2, TLR4 and TLR9 that recognize bacterial and viral pathogens are associated with BOS after lung transplantation.
Centre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
Elisabeth A
EA
Kastelijn
Coline H M
CH
van Moorsel
Ger T
GT
Rijkers
Henk J T
HJ
Ruven
Vincent
V
Karthaus
Johanna M
JM
Kwakkel-van Erp
E A
EA
van de Graaf
Pieter
P
Zanen
Diana A
DA
van Kessel
Jan C
JC
Grutters
Jules M M
JM
van den Bosch
D000328:Adult; D000483:Alleles; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9