Here, we have investigated several isotypes of EBV antibodies in cohorts of RA and SLE patients using an improved enzyme-linked immunosorbent assay (ELISA) setup and show that Epstein–Barr virus nuclear antigen (EBNA) 1 IgM discriminates efficiently between RA patients, SLE patients and healthy controls (HC)s. This evidence concerns the gene CD40LG and rheumatoid arthritis.