Serum concentration of immunoglobulin G-type antibodies against the whole Epstein–Barr nuclear antigen 1 and its aa35–58 or aa398–404 fragments in the sera of patients with systemic lupus erythematosus and multiple sclerosis

Abstract

SummarySeveral studies suggest that infection by Epstein-Barr 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-Epstein-Barr 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 aa35-58 and aa398-404 in 301 SLE patients, 135 MS 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 aa35-58 or aa398-404 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 < 0·001) 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 aa35-58 EBNA-1 fragment were elevated both in MS and SLE patients. By contrast, the levels of aa398-404 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 aa398-404 fragment are characteristic for SLE.

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

“…Studies have shown an increased number of latently EBV-infected cells [ 18 ] and an abnormally high viral load in the peripheral blood mononuclear cells of SLE patients [ 19 – 21 ]. Also, an impaired EBV-specific T cell response is observed in SLE patients [ 19 , 30 – 32 ] and an increased serologic response has been demonstrated with high titers of antibodies to EBV antigens in SLE patients compared to healthy controls [ 29 , 33 – 45 ].…”

High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

“…However, linear epitope mapping studies found serum IgG binding to EBNA1 398 -411 also in patients with systemic lupus erythematosus (SLE) (94) and in patients with infectious mononucleosis (a disease resulting from primary infection with EBV) (95) at elevated levels in comparison to healthy controls. The region was shown to cross-react with the sequence "PPPGMRPP" of the lupus spliceosomal autoantigen SNRPB (95,96). Moreover, as described above, the region contains the sequence motif "RRPFF" (EBNA1 402-406), which is also present in CRYAB (84).…”

“…Otherwise, in line with previous studies (88,90), serum IgG to EBNA1 52-100 were significantly more frequently observed in the MS group (Table II). A study with nasopharyngeal carcinoma (NPC) patients, however, also showed increased IgG and IgA reactivities to this region in comparison to healthy subjects (97), and antibodies to an epitope overlapping with this region (EBNA1 were found at higher concentrations in sera of both SLE and MS patients (96). Thus, EBNA1 52-100 harbors distinct epitopes, which explains the differences between the individual patients in the data for the four filtered peptides (see "Results").…”

Reduced response to Epstein–Barr virus antigens by T-cells in systemic lupus erythematosus patients

“…7-9 24 Furthermore, a serologic connection between EBV and SLE has been demonstrated by increased titres of antibodies to EBV antigens in SLE patients compared with healthy controls (HCs). 23 [25][26][27][28][29][30][31][32][33][34][35][36][37] Previous studies on EBV-specific T-cells are in discordance. Three individual studies have shown that SLE patients have fewer cytotoxic CD8 T-cells with a decrease in effector responses upon stimulation with EBV.…”