CHRONIC PARVOVIRUS B19 INFECTION INDUCES THE PRODUCTION OF ANTI-VIRUSANTIBODIES WITH AUTOANTIGEN BINDING-PROPERTIES

Human parvovirus B19 infection in adults shows some clinical features similar to those found in autoimmune connective tissue diseases. To be tter clarify the relationship between viral infection and autoimmunity , we have evaluated the ability of anti-parvovirus antibodies to speci fically recognize autoantigens in ten patients with chronic symmetric arthritis resembling rheumatoid arthritis or with recurrent episodes o f arthritis and cutaneous manifestations and persistence of specific I gM antibodies against B19 parvovirus. We synthetized a 24-amino acid i mmunodominant peptide corresponding to a part of the virus protein 1 a nd virus protein 2 overlapping region. The peptide has been used to te st patients' sera at different time points with an enzyme-linked immun osorbent assay (ELISA) and to purify antivirus antibodies by affinity chromatography on a peptide-Sepharose column. fluted immunoglobulins r ecognized the B19 peptide in both direct and competitive ELISA. Affini ty-purified anti-parvovirus antibodies were then tested on a panel of autoantigens including human keratin, collagen type II, thyreoglobulin , single-strand (ss)DNA, cardiolipin and ribonucleoprotein antigen Sm. fluted antibodies specifically recognized keratin, collagen type II, ssDNA and cardiolipin. Autoantibody activity was not detected in the i mmunoglobulin fraction after complete removal of anti-peptide antibodi es and in antibodies eluted from normal donors. Epstein-Barr virus-tra nsformed cell clones obtained from two subjects produced antibodies wh ich simultaneously recognize the viral peptide and several autoantigen s. To further confirm the role of the virus in inducing an autoantibod y response, eight BALB/c mice were immunized with the viral peptide co upled to a carrier protein. Autoantibody activity against keratin, col lagen II, cardiolipin and ssDNA was detected in six of the eight mice which developed a strong anti-virus response. Together, these data ind icate that B19 parvovirus may be linked to the induction of an autoimm une response.