Detection of Antibodies to a Recombinant gag Protein Derived from Human Endogenous Retrovirus Clone 4-1 in Autoimmune Diseases

To investigate whether human endogenous retroviruses (HERV) contribute to autoimmune diseases, we prepared a recombinant p30 ^gag protein derived from clone 4-1 of the HERV family, using a baculovirus-vector system. This p30 ^gag protein (CA41B) was approximately 30 kDa, as expected, and reacted with antibodies for p30 ^gag purified from both murine and feline leukemia virus. This result suggested that the antigenic determinant for p30 ^gag was well conserved in CA41B. Analysis of serum antibodies to p30 ^gag in patients with autoimmune diseases was done by Western blotting. CA41B detected anti-p30 ^gag antibodies in 48.3% of systemic lupus erythematosus (SLE) patients, 35.0% of Sjögren's syndrome (SS) patients, and 33.3% of mixed connective tissue disease (MCTD) patients, whereas no anti-p30 ^gag antibodies were found in healthy subjects. This suggested that HERV p30 ^gag or other retroviral p30 ^gag proteins possessing the same antigenic determinant as CA41B may play a role in these diseases. Although detection of antibodies to HERV p30 ^gag in autoimmune diseases is indirect evidence that HERV proteins are involved, this study showed that patients with autoimmune diseases have antibodies to HERV p30 ^gag using a recombinant HERV protein rather than synthetic peptides based on HERV or retroviral proteins of other species.