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

• Published in: The Journal of heart and lung transplantation Vol. 29; no. 6; pp. 665 - 671
• Main Authors: Kastelijn, Elisabeth A., MD, van Moorsel, Coline H.M., PhD, Rijkers, Ger T., PhD, Ruven, Henk J.T., PhD, Karthaus, Vincent, MSc, Kwakkel-van Erp, Johanna M., MD, van de Graaf, E.A., MD, PhD, Zanen, Pieter, MD, van Kessel, Diana A., MD, Grutters, Jan C., MD, PhD, van den Bosch, Jules M.M., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2010; Elsevier
• Subjects: Adult; Alleles; Biological and medical sciences; Bronchiolitis Obliterans - etiology; Bronchiolitis Obliterans - genetics; bronchiolitis obliterans syndrome; Cardiology. Vascular system; Chronic obstructive pulmonary disease, asthma; Female; Genotype; Humans; Immunity, Innate - genetics; innate immunity; lung transplantation; Lung Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Pneumology; Polymorphism, Genetic; Polymorphism, Single Nucleotide; single nucleotide polymorphisms; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Toll like receptors; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 9 - genetics; lung transplantation; innate immunity; bronchiolitis obliterans syndrome; single nucleotide polymorphisms; Toll like receptors; Respiratory disease; Lung; Transplantation; Homotransplantation; Immunity; Phlebology; Treatment; Gene; Surgery; Development; Graft; Bronchus disease; Bronchiolitis obliterans; Circulatory system; Cardiology; Polymorphism
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2009.12.013

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.