title: Pre-transplant antibodies to Kα1 tubulin and collagen-V in lung transplantation: clinical correlations.
abstract: BACKGROUND
  Immune responses to lung-associated self-antigens (SAgs) have been implicated in chronic lung allograft rejection. The goals of this study were to determine the prevalence of pre-existing antibodies (Abs) to the SAgs in pulmonary diseases and the association between pre-existing Abs to SAgs and the development of primary graft dysfunction (PGD), donor-specific antibodies (DSA), and chronic rejection.
  
  
  METHODS
  Pre- and post-transplant sera were analyzed from 317 lung transplant (LTx) recipients between 2000 and 2011 with diagnosis of chronic obstructive disease (n = 161), idiopathic pulmonary fibrosis (IPF; n = 50), cystic fibrosis (CF; n = 55), and others (n = 51). Samples were analyzed for Abs to SAgs by enzyme-linked immunosorbent assay, and DSA and cytokines by Luminex. The clinical diagnosis of PGD and bronchiolitis obliterans syndrome (BOS) was based on International Society for Heart and Lung Transplantation guidelines.
  
  
  RESULTS
  The overall prevalence of Abs to SAgs was 22.71%, including 18% in chronic obstructive pulmonary disease (p = 0.033), 34% in IPF (p = 0.0006), 29% in CF (p = 0.0023), and 19.6% in other diagnoses (p = 0.044). The incidence of PGD (88% vs 54%, p < 0.05), DSA (70% vs 45%, p < 0.01), and BOS (90% vs 38% (p < 0.001) after LTx was significantly higher in patients with pre-LTx Abs to SAgs than without. Pro-inflammatory cytokines (interleukin-1β, interleukin-17, and interferon-γ) were elevated in patients who had pre-LTx Abs to SAgs, along with a reduction in anti-inflammatory interleukin-10.
  
  
  CONCLUSIONS
  Patients with IPF and CF have the highest prevalence of Abs to SAgs. Patients with pre-existing Abs to SAgs are at increased risk for development of PGD, DSA, and BOS. Strategies to remove pre-existing Abs to SAgs should be considered to improve lung allograft outcome.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Venkataswarup
authors.initials: V
authors.lastname: Tiriveedhi
authors.forename: Baskaran
authors.initials: B
authors.lastname: Gautam
authors.forename: Nayan J
authors.initials: NJ
authors.lastname: Sarma
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.forename: Marie
authors.initials: M
authors.lastname: Budev
authors.forename: Aviva
authors.initials: A
authors.lastname: Aloush
authors.forename: Ramsey
authors.initials: R
authors.lastname: Hachem
authors.forename: Elbert
authors.initials: E
authors.lastname: Trulock
authors.forename: Bryan
authors.initials: B
authors.lastname: Myers
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Patterson
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000906:Antibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D024062:Collagen Type V / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D055031:Primary Graft Dysfunction / Q000276:immunology; D014019:Tissue Donors; D014404:Tubulin / Q000276:immunology*
chemical_list: D000906:Antibodies; D001324:Autoantigens; D024062:Collagen Type V; D014404:Tubulin
keywords: alloimmunity; autoimmunity; bronchiolitis obliterans syndrome; cytokines; primary graft dysfunction