Springer Seminars in Immunopathology

, Volume 17, Issue 2–3, pp 203–230

The Epstein-Barr virus in autoimmunity

  • John H. Vaughan
Article

Conclusions

EBV, which is one of the viruses that most of us live with throughout most of our lifetimes, is capable of inducing autoantibodies reactive with a variety of normal tissue proteins. Because of this, the virus remains a constant threat for autoimmunization during our lifetimes, and this threat is in fact realized in several autoimmune diseases. We have described here manifestations suggesting this in RA, SjS, SLE, SSc and MS. In RA, MS, and SSc, autoantibodies cross-reactive with the glycine/alanine repeat of EBNA-1 exist, but these cross-reactions seem to be subtly different among the three. In SSc, cross-reacting autoantibody is expressed as anti-p542, while in RA an anti-60 kDa activity without anti-p542 is generally present. In MS cross-reacting autoantibody to an 80- to 82-kDa doublet is predominant.

In SjS and SLE, the autoimmune manifestations are distinctly different from those of the preceding three diseases. In SLE, cross-reacting autoantibody (anti-Sm) is predominantly based on glycine/arginine sequences in EBNA-1, or on its PPPGRRP sequence. In SjS, productive infection by the virus is a dominant feature of the illness, and the principal autoantibodies, anti-Ro/SS-A and anti-La/SS-B, are not derived by cross-reactivity with EBNA-1 or any other EBV protein. Anti-La/SSB may conceivably be derived either from an abnormal display of the autoantigen on the outer cell membrane, or by binding of the autoantigen by EBV-generated EBER molecules.

We have presented no evidence that these autoimmune manifestations are pathogenetically significant, but we believe that further study may prove some or all to be so. This question can be most effectively explored using recombinant EBNA-1 as antigen in selected mouse strains. Further exploration in man will require cloning and identification of the 80- to 82-kDa and ∼ 60-kDa antigens from human neuroglial or lymphocytic cDNA libraries, to clarify the nature of these molecules and explore the ways in which they may be exposed to the immune system in disease. Completion of the sequencing and identification of p542 is needed for the same reasons. Other EBV antigens can be similarly explored, and we have mentioned studies of this nature that are already under way by others using EBV gp 110.

It is highly likely that all autoimmune diseases are significantly impacted by multiple microbial agents, and that final expression of disease in these syndromes is a resultant of all these impactions together. Nevertheless, the number of agents making significant autoimmune contributions is probably limited, and even the number of inciting molecules from a given agent may be limited, so the process may not be so multidispersed as to make an investigation of this part of the autoimmune disease unmanageable. We can even hope that ultimately this approach will provide a useful road towards prevention or therapy.

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • John H. Vaughan
    • 1
  1. 1.Department of MedicineUniversity of California, San DiegoLa JollaUSA

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