Immune responses to collagen-IV and fibronectin in renal transplant recipients with transplant glomerulopathy

Am J Transplant. 2014 Mar;14(3):685-93. doi: 10.1111/ajt.12592. Epub 2014 Jan 10.


Antibodies (Abs) to donor HLA (donor-specific antibodies [DSA]) have been associated with transplant glomerulopathy (TG) following kidney transplantation (KTx). Immune responses to tissue-restricted self-antigens (self-Ags) have been proposed to play a role in chronic rejection. We determined whether KTx with TG have immune responses to self-Ags, Collagen-IV (Col-IV) and fibronectin (FN). DSA were determined by solid phase assay, Abs against Col-IV and FN by enzyme-linked immunosorbent assay and CD4+ T cells secreting interferon gamma (IFN-γ), IL-17 or IL-10 by ELISPOT. Development of Abs to self-Ags following KTx increased the risk for TG with an odds ratio of 22 (p-value = 0.001). Abs to self-Ags were IgG and IgM isotypes. Pretransplant Abs to self-Ags increased the risk of TG (22% vs. 10%, p < 0.05). Abs to self-Ags were identified frequently in KTx with DSA. TG patients demonstrated increased Col-IV and FN specific CD4+ T cells secreting IFN-γ and IL-17 with reduction in IL-10. We conclude that development of Abs to self-Ags is a risk factor and having both DSA and Abs to self-Ags increases the risk for TG. The increased frequency of self-Ag-specific IFN-γ and IL-17 cells with reduction in IL-10 demonstrate tolerance breakdown to self-Ags which we propose play a role in the pathogenesis of TG.

Keywords: Alloimmunity; Collagen-IV; autoimmunity; fibronectin; kidney transplantation; transplant glomerulopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood*
  • Autoantigens / immunology*
  • Collagen Type IV / immunology*
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibronectins / immunology*
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / immunology*
  • HLA Antigens / immunology
  • Humans
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors


  • Autoantibodies
  • Autoantigens
  • Collagen Type IV
  • Cytokines
  • Fibronectins
  • HLA Antigens
  • Isoantibodies