title: Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection.
abstract: BACKGROUND
  Chronic human lung allograft rejection, represented by bronchiolitis obliterans syndrome (BOS), is the single most important factor that limits the long-term survival following lung transplantation (LT). However, the pathogenesis of BOS remains unclear. We hypothesized that the early posttransplant inflammation would promote the development of donor anti-human leukocyte antigen (HLA) alloimmunity and predispose to BOS.
  
  
  METHODS
  Serum levels of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, IP-10, MIG, MCP-1, MIP-1alpha, MIP-1beta, RANTES, tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-gamma, granulocyte-macrophage colony-stimulating factor, IL-1Ralpha, and IL-2R were serially analyzed in 31 BOS+ and matched 31 BOS- patients using quantitative multiplex bead immunoassays. Donor-specific HLA class II cellular immunity was analyzed using enzyme-linked immunospot (ELISPOT) by testing recipient peripheral blood mononuclear cells against mismatched donor HLA-DR peptides. Anti-HLA class II antibodies were monitored using flow panel reactive antibodies.
  
  
  RESULTS
  There was early posttransplant elevation in basal serum levels of proinflammatory chemokines IP-10 and MCP-1 and Th1-cytokines IL-1beta, IL-2, IL-12, and IL-15 in BOS+ patients, compared to BOS- and normal subjects. In addition, a threefold decline in IL-10 levels was found during BOS development. BOS+ patients revealed increased development of HLA class II alloantibodies and Th1-predominant donor-specific cellular immunity with high frequency of IFN-gamma and low IL-5 producing T-cells.
  
  
  CONCLUSIONS
  Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ankit
authors.initials: A
authors.lastname: Bharat
authors.forename: Kishore
authors.initials: K
authors.lastname: Narayanan
authors.forename: Tyler
authors.initials: T
authors.lastname: Street
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.forename: Nancy
authors.initials: N
authors.lastname: Steward
authors.forename: Aviva
authors.initials: A
authors.lastname: Aloush
authors.forename: Brian
authors.initials: B
authors.lastname: Meyers
authors.forename: Richard
authors.initials: R
authors.lastname: Schuessler
authors.forename: Elbert P
authors.initials: EP
authors.lastname: Trulock
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Patterson
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D001989:Bronchiolitis Obliterans / Q000097:blood / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D008168:Lung; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators