Virus infection induces redistribution and membrane localization of the nuclear antigen La (SS-B): a possible mechanism for autoimmunity.

To investigate the possibility that anti-La (SS-B) antibodies in Sjögren's syndrome were induced by virus infection we studied the distribution of La in virus-infected human cell lines. Three monoclonal antibodies to La were used with monoclonal anti-Sm (derived from MRL/lpr lupus mice) and anti-rat immunoglobulin antibodies as controls. In uninfected cells La was predominantly in the nucleus. Twenty-four hours after infection of HEp-2 cells with adenovirus 2, the La and Sm antigens appeared to aggregate and accumulate in the periphery of the nucleus and, after 48 h, La was seen in the cytoplasm and cell membrane. No cytoplasmic or membrane expression of Sm was seen. Infection with adenovirus or cytomegalovirus caused a 2-13-fold increase in the concentration of La in three cell lines. Treatment of HE--2 cells with interferon-gamma (IFN-gamma) and infection with Epstein-Barr virus and cytomegalovirus caused cytoplasmic, but no definite membrane expression of La. The appearance of La on the surface of virally infected epithelial cells together with IFN-gamma induced class II expression could form the basis of a T cell dependent mechanism for anti-La autoantibody induction.

Titers of antibodies to RANA in rheumatoid arthritis and normal sera. Relationship to Epstein-Barr virus infection.

The disease specificity of antibodies to rheumatoid arthritis nuclear antigen (RANA) was examined by comparing anti-RANA titers in sera from 100 patients with rheumatoid arthritis (RA) with sera from 93 healthy controls. Anti-RANA antibodies were found in 86% of the RA sera and 56% of the controls. The higher titers in the RA sera were unrelated to clinical features or to measurements of circulating immune complexes or rheumatoid factors. To study the relationship of these antibodies to previous Epstein-Barr virus (EBV) infection, antibodies to the EB virus capsid antigen (VCA) were examined and found in 94% of the RA sera and 97% of the adult controls. Four of the six RA sera without anti-VCA antibodies had detectable anti-RANA antibodies, so that we might suggest anti-RANA can arise in the absence of EBV infection. From absorption experiments with non-EBV transformed extracts, we inferred that high anti-RANA titers could be due to reactions with non-Epstein-Bar virus related nuclear antigens. These data cast doubt on current speculation about a possible pathogenic role for Epstein-Barr virus in this disease.

Measurement of immunoglobulin production by peripheral blood mononuclear cells in vitro using a solid-phase immunoradiometric assay.

A simple solid-phase immunoradiometric assay for IgG and IgM is described. Supernatants from lymphocyte cultures are incubated in microtitre plates which have been precoated with anti-IgG or anti-IgM. Subsequent binding of 125I-labelled anti-immunoglobulin is measured and IgG and IgM in supernatants are estimated from the standard curve constructed for each assay. The assay is specific for human IgG and IgM, is able to detect nanogram amounts and offers advantages over other techniques for evaluating in vitro lymphocyte function.