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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: 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.
Authors: Emily S Charlson; Joshua M Diamond; Kyle Bittinger; Ayannah S Fitzgerald; Anjana Yadav; Andrew R Haas; Frederic D Bushman; Ronald G Collman Journal: Am J Respir Crit Care Med Date: 2012-07-12 Impact factor: 21.405
Authors: J M Kwakkel-van Erp; A W M Paantjens; D A van Kessel; J C Grutters; J M M van den Bosch; E A van de Graaf; H G Otten Journal: Clin Exp Immunol Date: 2011-06-27 Impact factor: 4.330
Authors: Joshua M Diamond; Nuala J Meyer; Rui Feng; Melanie Rushefski; David J Lederer; Steven M Kawut; James C Lee; Edward Cantu; Rupal J Shah; Vibha N Lama; Sangeeta Bhorade; Maria Crespo; Ejigayehu Demissie; Joshua Sonett; Keith Wille; Jonathan Orens; Ann Weinacker; David Weill; Selim Arcasoy; Pali D Shah; John A Belperio; David Wilkes; Lorraine B Ware; Scott M Palmer; Jason D Christie Journal: Am J Respir Crit Care Med Date: 2012-07-19 Impact factor: 21.405
Authors: Joshua M Diamond; Tatiana Akimova; Altaf Kazi; Rupal J Shah; Edward Cantu; Rui Feng; Matthew H Levine; Steven M Kawut; Nuala J Meyer; James C Lee; Wayne W Hancock; Richard Aplenc; Lorraine B Ware; Scott M Palmer; Sangeeta Bhorade; Vibha N Lama; Ann Weinacker; Jonathan Orens; Keith Wille; Maria Crespo; David J Lederer; Selim Arcasoy; Ejigayehu Demissie; Jason D Christie Journal: Am J Respir Crit Care Med Date: 2014-03-01 Impact factor: 21.405
Authors: Kevin Budding; Jessica van Setten; Eduard A van de Graaf; Oliver A van Rossum; Tineke Kardol-Hoefnagel; Erik-Jan D Oudijk; C Erik Hack; Henderikus G Otten Journal: Front Immunol Date: 2017-09-06 Impact factor: 7.561