Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection

Ann Thorac Surg. 2010 Oct;90(4):1094-101. doi: 10.1016/j.athoracsur.2010.06.009.


Background: Primary graft dysfunction (PGD) is a known risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Here, we report that preformed antibodies to self-antigens increase PGD risk and promote BOS.

Methods: Adult lung transplant recipients (n = 142) were included in the study. Primary graft dysfunction and BOS were diagnosed based on International Society for Heart and Lung Transplantation guidelines. Antibodies to self-antigens k-alpha-1 tubulin, collagen type V, and collagen I were quantitated using standardized enzyme-linked immunosorbent assays, and cytokines were analyzed using Luminex immunoassays (Biosource International, Camirillo, CA). Human leukocyte antigen (HLA) antibodies were measured using Flow-PRA (One Lambda, Canoga Park, CA).

Results: Lung transplant recipients with pretransplant antibodies to self-antigens had increased risk of PGD (odds ratio 3.09, 95% confidence interval: 1.2 to 8.1, p = 0.02) compared with recipients without. Conversely, in patients with PGD, 34.7% were positive for pretransplant antibodies whereas in the PGD negative group, only 14.6% had antibodies (p = 0.03). Antibody positive patients demonstrated high levels of proinflammatory cytokines interleukin (IL)-1β (2.1-fold increase), IL-2 (3.0), IL-12 (2.5), IL-15 (3.0), and chemokines interferon-inducible protein-10 (3.9) and monocyte chemotactic protein-1 (3.1; p < 0.01 for all). On 5-year follow-up, patients without antibodies showed greater freedom from development of HLA antibodies compared with patients who had antibodies (class I: 67% versus 38%, p = 0.001; class II: 71% versus 41%, p < 0.001). Patients with pretransplant antibodies were found to have an independent relative risk of 2.3 (95% confidence interval: 1.7 to 4.5, p = 0.009) for developing BOS.

Conclusions: Presence of antibodies to self-antigens pretransplant increases the risk of PGD immediately after transplant period and BOS on long-term follow-up. Primary graft dysfunction is associated with an inflammatory cascade that augments the alloimmune (anti-HLA) response that predisposes to BOS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Bronchiolitis Obliterans / immunology*
  • Chronic Disease
  • Collagen Type I / immunology
  • Collagen Type V / immunology
  • Female
  • Graft Rejection / immunology
  • Humans
  • Lung Transplantation / adverse effects
  • Lung Transplantation / immunology*
  • Male
  • Middle Aged
  • Primary Graft Dysfunction / immunology*
  • Risk Factors
  • Tubulin / immunology


  • Autoantibodies
  • Autoantigens
  • Collagen Type I
  • Collagen Type V
  • Tubulin