Two short autoepitopes on the nuclear dot antigen are similar to epitopes encoded by the Epstein-Barr virus.

Abstract

To understand the relationship between antibodies present in patients with anti-nuclear dot (ND) autoimmune disease and the proteins they recognize, epitopes that react with the autoantibodies were mapped. A panel of fusion proteins containing different portions of the ND protein were overproduced in Escherichia coli. Immunoblot analysis with anti-ND antibodies revealed that most (10 of 12) sera recognize two major autoepitopes that are each a maximum of 8 amino acids long. The other two sera recognize one of the two epitopes. In addition to the short linear autoepitopes, a conformational epitope appears to be present on the ND antigen. Each of the two linear epitope sequences shares sequence similarities with those of several viral proteins found in the databases. Furthermore, two fusion proteins containing short Epstein-Barr virus (EBV) protein sequences that are similar to the ND epitopes were recognized by the human autoimmune sera, indicating that the autoepitopes are present in EBV protein sequences. Our results are consistent with the hypothesis that ND autoimmune disease might be associated with EBV infections. Anti-nuclear antibodies are found in a variety of different autoimmune disease patients. In many cases, the reactivity of the antibody produced often correlates with the particular disease (e.g., ref. 1). Despite this fact, the etiology of both the disease and antibodies is unknown. Furthermore, since many autoantigens reside in the nucleus and are, therefore, presumably inaccessible to autoantibodies, it is also unclear to what extent the antibodies contribute to the pathogenesis, especially in the initial stages of the autoimmune disease.Several models have been proposed to account for the etiology and pathogenesis of autoimmune disease. One of these, the molecular mimicry model (2), states that an infecting agent such as a bacteria or virus might be involved in the onset or pathology of the disease. Antibodies produced against the infecting agent might cross-react with cellular antigens and, potentially, contribute to the disease state.Recently, efforts have been directed toward mapping epitopes recognized by antibodies isolated from patients with different types of autoimmune diseases. Thus far, epitopes have been mapped for a variety of different autoantigens, and some of these are similar to viral sequences (3-6). For example, autoepitopes have been mapped on the a subunit of the acetylcholine receptor that is associated with myasthenia gravis (3) and on the diffuse systemic sclerosis antigen DNA topoisomerase I (4). The a subunit of acetylcholine receptor exhibits immunological cross-reactivity with a homologous domain on herpes simplex virus glycoprotein D (3), while the antigenic 11-amino acid region of DNA topoisomerase I contains a 6-amino acid sequence that is identical to a sequence present in the group-specific antigen (p309ag) of some mammalian retroviruses (4). However, the usefulness of these studies is limited because in most instances mapping was doneThe publication cost...

Genome‐wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis

“…(36) Two major linear epitope sequences recognized by anti-sp100 share sequence similarities with several viral proteins found in the Epstein-Barr virus protein sequences. (37) In our analysis, we found HLA-DRβ1-Asn77/Arg74, DRβ1-Ser37, and HLA-DPβ1-Lys65 associated with the sp100 autoantibody. All of these AAs locate within the peptide-binding grooves, which imply a functional impact of sp100 epitope presentation in autoantibody production.…”

Epstein-Barr Virus–Infected Plasma Cells Infiltrate Erosive Oral Lichen Planus

“…Our results indicate that OLP activity, which mainly reflects damage to the basal epithelial layer, strongly correlates with levels of EBV infection. One attractive hypothesis could be that EBV plays a direct role in keratinocyte destruction during OLP, since molecular mimicry between EBV proteins and self-proteins was shown to favor autoimmune reactions (Xie and Snyder 1995). This important issue should be the focus of particular attention for future investigations.…”

Epstein-Barr Virus as a Trigger of Autoimmune Liver Diseases

“…As mentioned, EBV antigens that could serve as targets of cross-reactive antibodies specific for human PDC-E2 have not been found [ 145 ]. However, other groups have examined cross-reactivity between EBV sequences and sp100, the major nuclear body autoantigen of PBC-specific anti-MND antibody responses [ 146 ]. These antibodies are found in approximately 30% of PBC patients, and those of the IgG3 subclass have been associated with a more severe disease progression [ 89 ].…”