title: Efficacy of extracorporeal photopheresis in clearance of antibodies to donor-specific and lung-specific antigens in lung transplant recipients.
abstract: BACKGROUND
  Extracorporeal photopheresis (ECP) has been used to treat chronic rejection after lung transplantation (LTx). We investigated the effect of ECP on several immune parameters that have been associated with poor lung function, including donor-specific antibodies (DSA) to human leukocyte antigen (HLA), antibodies against the lung-associated self-antigens (SAg), Kα1-tubulin (Kα1T), collagen I and V, and circulating levels of pro-inflammatory and anti-inflammatory cytokines.
  
  
  METHODS
  Sera were collected from post-LTx patients diagnosed with bronchiolitis obliterans before and 6 months after initiation of ECP. DSA and cytokine levels were measured by Luminex (Invitrogen, Carlsbad, CA). Changes in lung function over the 6 months preceding and after the initiation of ECP were measured by retrospective analysis of spirometry performed at routine clinic visits.
  
  
  RESULTS
  ECP was associated with a significant decline in DSA levels as well as antibodies to lung-associated SAg. ECP also reduced circulating levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. These immunologic changes were associated with a significant 63% reduction in the rate of decline in forced expiratory volume in 1 second over a 1-year period. Though statistically insignificant, a higher rate of clearance of antibodies to lung-associated SAg was strongly associated with better response to ECP.
  
  
  CONCLUSIONS
  ECP is associated with a reduction in the levels of circulating DSA, antibodies to lung-associated SAg (Kα1T, collagen I, and collagen V), and circulating levels of several pro-inflammatory cytokines. We propose that these changes contribute to the beneficial effect of ECP in reducing the decline in lung function.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gautam
authors.initials: G
authors.lastname: Baskaran
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Venkataswarup
authors.initials: V
authors.lastname: Tiriveedhi
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Sabarinathan
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Aviva
authors.initials: A
authors.lastname: Aloush
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Brenda
authors.initials: B
authors.lastname: Grossman
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ramsey
authors.initials: R
authors.lastname: Hachem
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: kumart@wustl.edu.
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D024042:Collagen Type I / Q000276:immunology; D024062:Collagen Type V / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D017893:Photopheresis / Q000379:methods*; D012189:Retrospective Studies; D014019:Tissue Donors; D066027:Transplant Recipients; D016896:Treatment Outcome; D014404:Tubulin / Q000276:immunology
chemical_list: D000906:Antibodies; D001324:Autoantigens; D024042:Collagen Type I; D024062:Collagen Type V; D016207:Cytokines; D006680:HLA Antigens; C533522:TUBA1A protein, human; D014404:Tubulin
keywords: chronic rejection; cytokines; donor-specific antibodies; extracorporeal photopheresis; lung transplantation