Serum concentration of immunoglobulin G-type antibodies against the whole EpsteinBarr nuclear antigen 1 and its aa3558 or aa398404 fragments in the sera of patients with systemic lupus erythematosus and multiple sclerosis

Several studies suggest that infection by EpsteinBarr virus (EBV) might be one of the environmental factors which facilitates the development of autoimmune disorders in genetically susceptible individuals. Recent data indicate that high anti-EpsteinBarr nuclear antigen 1 (EBNA)-1 immunoglobulin (Ig)G titre is a strong risk factor for multiple sclerosis (MS) in patients both with and without the main genetic predisposing trait, human leucocyte antigen (HLA)-DRB1*15:01. Because no similar studies have been published in systemic lupus erythematosus (SLE) patients, we determined the HLA-DRB1*15:01 carrier state and the serum titres against the whole EBNA-1 and its small fragments aa3558 and aa398404 in 301 SLE patients, 135MS patients and in 345 healthy controls. The carrier state of the HLA-DRB1*15:01 allele was deduced from genotyping of a tagSNP (rs3135388) by applying a Taqman-based assay. The serum concentrations of antibodies to EBNA-1 and its aa3558 or aa398404 fragments were determined using a commercial assay (ETI-EBNA-G) and home-made enzyme-linked immunosorbent assays, respectively. The serum concentration of anti-EBNA-1 antibodies was significantly (P<0 center dot 001) higher both in MS and SLE patients than in controls. Similar significant differences were found both in HLA-DRB1*15:01 carriers and non-carriers. Furthermore, titres of antibodies against the aa3558 EBNA-1 fragment were elevated both in MS and SLE patients. By contrast, the levels of aa398404 EBNA-1 antibodies were elevated significantly only in the SLE patients. These findings indicate that high anti-EBNA-1 IgG titres are HLA-DRB1*15:01-independent risk factors not only for MS, but also for SLE, while high antibody titres against the aa398404 fragment are characteristic for SLE.