A novel mechanism for virus-induced autoimmunity in humans

Immunol Rev. 1996 Aug;152:175-92. doi: 10.1111/j.1600-065x.1996.tb00916.x.

Abstract

A novel mechanism for virus-induced autoimmunity in humans is described. Infection of immunocompromised bone marrow-transplanted patients with human CMV results in the formation of autoantibodies specific for the cell-surface protein CD13 (aminopeptidase N). CD13 is present on all CMV-susceptible cells and infection can be specifically blocked by antibodies against CD13. CMV particles carry CD13, which is incorporated in the viral envelope during budding of viral nucleo-capsids into Golgi-derived vacuoles. Antibodies against CD13 are virus-neutralizing, in efficiency comparable to antibodies against viral envelope glycoproteins. Autoantibodies against CD13 are present in patients who develop chronic GVHD following allogeneic bone marrow transplantation. This lesion shows striking similarities to certain autoimmune diseases in humans, of which scleroderma is one example. In vivo binding of antibodies to tissue structures known to be targets for chronic GVHD has been demonstrated in patients with chronic GVHD. Finally, patient serum containing CD13-specific antibodies binds to skin and mucosa tissue sections in vitro, a binding which is inhibited by CD13-specific monoclonal antibodies. Thus a virus infection can activate an immune response against a specific autoantigen, providing possibilities for destruction of non-infected host cells, as originally proposed by Fujinami & Oldstone (1985), and also for the molecular mimicry model for induction of autoimmunity. Our findings lend support to the idea that inhibiting the transfer of CMV infection in bone marrow transplants will reduce morbidity and mortality from CMV infection but will also reduce the incidence of chronic GVHD. Elimination of CD13+ cells in bone marrow is not believed to interfere with the chance of recipient repopulation, and may be a way to decrease morbidity and mortality substantially following BMT. For all patients, every effort should be taken to prevent a post-BMT CMV infection in order to reduce the risk of the later development of chronic GVHD.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cytomegalovirus / immunology
  • Graft vs Host Disease / immunology
  • Humans
  • Viruses / immunology*