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

Ankit Bharat, Kishore Narayanan, Tyler Street, Ryan C. Fields, Nancy Steward, Aviva Aloush, Brian Meyers, Richard Schuessler, Elbert P. Trulock, G. Alexander Patterson, Thalachallour Mohanakumar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

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)-1β, 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-1α, MIP-1β, RANTES, tumor necrosis factor (TNF)-α, interferon (IFN)-α, IFN-γ, granulocyte-macrophage colony-stimulating factor, IL-1Rα, 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-1β, 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-γ and low IL-5 producing T-cells. CONCLUSION. Early posttransplant elevation of proinflammatory mediators is associated with alloimmunity and chronic human lung allograft rejection.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalTransplantation
Volume83
Issue number2
DOIs
StatePublished - Jan 2007

Keywords

  • Alloimmunity
  • Bronchiolitis obliterans syndrome
  • HLA class II
  • Inflammation
  • Lung transplantation

ASJC Scopus subject areas

  • Transplantation

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