Polymorphisms in innate immunity genes associated with development of bronchiolitis obliterans after lung transplantation

published online 15 March 2010.

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 BOSpos patients and BOSneg patients and controls. The BOSpos group had significantly more patients with 3 or 4 of these risk alleles compared with the BOSneg and control groups.

Conclusions

Polymorphisms in TLR2, TLR4 and TLR9 that recognize bacterial and viral pathogens are associated with BOS after lung transplantation.

Keywords: innate immunity, bronchiolitis obliterans syndrome, lung transplantation, Toll like receptors, single nucleotide polymorphisms

a Centre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Nieuwegein

b Laboratory of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein

c Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein

d Division of Heart and Lungs, University Medical Centre Utrecht, Utrecht, The Netherlands

Reprint requests: J.C. Grutters, MD, Centre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Postbox 2500, 3420 EM Nieuwegein, The Netherlands. Telephone: +31-0-30-609-2428. Fax: +31-0-30-605-2001

PII: S1053-2498(09)01534-4

doi:10.1016/j.healun.2009.12.013

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