Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection

Transplantation. 2007 Jan 27;83(2):150-8. doi: 10.1097/01.tp.0000250579.08042.b6.

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.

Conclusion: Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchiolitis Obliterans / blood
  • Bronchiolitis Obliterans / immunology
  • Chronic Disease
  • Female
  • Graft Rejection / blood*
  • Graft Rejection / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation Mediators / blood
  • Inflammation Mediators / immunology
  • Lung
  • Lung Transplantation / adverse effects*
  • Lung Transplantation / immunology*
  • Male
  • Middle Aged
  • Th1 Cells / metabolism
  • Time Factors
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / immunology

Substances

  • Histocompatibility Antigens Class II
  • Inflammation Mediators