title: Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome.
abstract: Chronic lung allograft dysfunction (CLAD) is the major factor limiting long-term success of lung transplantation. Polymorphisms of surfactant protein D (SP-D), an important molecule within lung innate immunity, have been associated with various lung diseases. We investigated the association between donor lung SP-D polymorphisms and posttransplant CLAD and survival in 191 lung transplant recipients consecutively transplanted. Recipients were prospectively followed with routine pulmonary function tests. Donor DNA was assayed by pyrosequencing for SP-D polymorphisms of two single-nucleotide variations altering amino acids in the mature protein N-terminal domain codon 11 (Met(11) Thr), and in codon 160 (Ala(160) Thr) of the C-terminal domain. CLAD was diagnosed in 88/191 patients, and 60/191 patients have died. Recipients of allografts that expressed the homozygous Met(11) Met variant of aa11 had significantly greater freedom from CLAD development and better survival compared to those with the homozygous Thr(11) Th variant of aa11. No significant association was noted for SP-D variants of aa160. Lung allografts with the SP-D polymorphic variant Thr(11) Th of aa11 are associated with development of CLAD and reduced survival. The observed genetic differences of the donor lung, potentially with their effects on innate immunity, may influence the clinical outcomes after lung transplantation.
authors.affiliation: Lung Transplant Program, Columbia University, New York, NY, USA.
authors.forename: B
authors.initials: B
authors.lastname: Aramini
authors.forename: C
authors.initials: C
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Diangelo
authors.forename: E
authors.initials: E
authors.lastname: Petersen
authors.forename: D J
authors.initials: DJ
authors.lastname: Lederer
authors.forename: L
authors.initials: L
authors.lastname: Shah
authors.forename: H
authors.initials: H
authors.lastname: Robbins
authors.forename: J
authors.initials: J
authors.lastname: Floros
authors.forename: S M
authors.initials: SM
authors.lastname: Arcasoy
authors.forename: J R
authors.initials: JR
authors.lastname: Sonett
authors.forename: F
authors.initials: F
authors.lastname: D'Ovidio
mesh_terms: D000328:Adult; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000401:mortality*; D006801:Humans; D007113:Immunity, Innate; D008171:Lung Diseases / Q000150:complications* / Q000235:genetics / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011183:Postoperative Complications; D011446:Prospective Studies; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D
keywords: Lung allograft immunity; lung transplantation; polymorphisms; pulmonary surfactant proteins