Presence of anti-La(SS-B) is associated with binding to the 13-kD carboxyl terminus of 60-kD Ro(SS-A) in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE) clinical manifestations, autoantibody production, and immunogenetics are inter-related. The ability to study parts of the autoimmune response may allow a more detailed understanding of these relationships. We undertook this study to determine whether the fine specificity of the autoimmune response to 60-kD Ro(SS-A) was related to the presence of other autoantibodies. We screened 74 patients with SLE for antibodies to the carboxyl 13-kD terminal of 60-kD Ro(SS-A) (13 kD). Twenty-five sera had such antibodies. This reactivity was distinguished by the presence of not only anti-Ro(SS-A) but also other antibodies. All nine sera with Ro(SS-A) and La(SS-B) Ouchterlony immunodiffusion precipitins bound 13-kD (p = 0.01), whereas 10 of 11 sera with both anti-Ro(SS-A) and anti-La(SS-B) as determined by immunosorbent assay bound 13-kD (p = 0.002). Inhibition studies demonstrated that antibodies binding the 13-kD fragment bound the 60-kD Ro(SS-A) protein but did not bind the La(SS-B) protein. Thus, anti-La(SS-B) was found in those sera that bound epitopes within the 13-kD carboxyl terminal of 60-kD Ro(SS-A). These data suggest a structural basis by which anti-Ro(SS-A) and anti-La(SS-B) are coupled in SLE.

Antibodies to vesicular stomatitis virus proteins in patients with systemic lupus erythematosus and in normal subjects.

OBJECTIVE: To determine the presence of antibodies that bind vesicular stomatitis virus (VSV) proteins in systemic lupus erythematosus (SLE) patient sera, as well as to examine any relationship between antibodies binding the viral nucleocapsid (N) protein and anti-Ro autoantibodies. METHODS: Eighty SLE patient sera, 80 normal control sera, 47 rheumatic disease patient control sera, and 9 sera from Panamanian subjects (6 of whom were infected with VSV) were evaluated by immunoblot of purified VSV proteins. RESULTS: Findings on immunoblots of the Panamanian subjects' sera were consistent with histories of endemic exposure to VSV, as determined by virus neutralization assays. Significantly different binding to viral proteins was seen in the group of 80 SLE patients compared with the normal control group and with the rheumatic disease control group, by a variety of measures. For example, most of the reactivity in the SLE patient sera included binding to the internal viral matrix (M) and N proteins, while the reactivity in the normal control sera was mostly against the surface viral glycoprotein (G) protein alone or the N protein alone. Within this SLE patient cohort, associations were found between binding to N protein and anti-Ro precipitins and between binding to M protein and anti-nuclear RNP autoantibody precipitins. CONCLUSION: The data are consistent with the original specific hypotheses of a relationship between 60-kd Ro autoantigenicity and VSV, as well as with the suggestion that a rhabdovirus may be important in SLE. They do not, however, make possible any conclusions concerning the role of rhabdoviruses in the development of SLE or of anti-Ro autoimmunity.

Cooperative association of T cell beta receptor and HLA-DQ alleles in the production of anti-Ro in systemic lupus erythematosus.

The immunogenetics of the autoantibody response to Ro (or SS-A) have been explored in patients with systemic lupus erythematous. Data show that alleles of the T cell beta receptor and HLA-DQ loci are cooperatively associated with the presence of anti-Ro autoantibodies in systemic lupus erythematosus. Identification of HLA-DQ by oligonucleotide probe binding to polymerase chain reaction products demonstrates that the combination of DQB1*0201 and one of DQA1*0101, DQA1*0102, or DQA1*0103 is associated with anti-Ro. Patients possessing a particular pair of T cell receptor beta restriction enzyme polymorphisms along with these specific HLA-DQ alleles produce quantitatively more anti-Ro as measured by a sensitive solid-phase immunoassay than patients without these T cell receptor and DQ alleles. Other work has shown that the autoimmune response is directed against the human Ro antigen. These results are consistent with a central role in the disregulation of autoimmunity involving a trimolecular complex composed of the autoantigen bound by a HLA-DQ molecule which, together, are bound in turn by T cells which express a particular subset of T cell receptors.

Immunogenetics of epitopes of the carboxyl terminus of the human 60-kD Ro autoantigen.

Systemic lupus erythematosus is associated with the presence of autoantibodies which bind several ribonucleoproteins, including Ro (or SS-A). We have explored the relationship of the HLA-DQ and T cell receptor alleles in patients producing autoantibodies binding the 13-kD carboxyl terminus fragment of the 60-kD Ro and with autoantibodies binding a peptide epitope within this fragment (amino acid residues 480-494). Antibodies binding the 13-kD fragment are more likely to be found in the sera of patients with particular DQA1 and DQB1 alleles, while antibodies binding the epitope at 480-494 are found almost exclusively in the sera of patients with a Bg/II 9.8-kb polymorphism of the T cell receptor beta gene. Meanwhile, in these same patient sera the level of autoantibodies binding the complete 60-kD Ro particle is associated with a distinct pattern of alleles at these same immunoregulatory loci. These data demonstrate that component parts of autoantibody responses may be under genetic control which can be distinguished from the HLA associations characteristic of the response to the intact, complete autoantigen.