Abstract: Optimization and validation of a serum test confirms symptomatic autoimmune diseases e.g. multiple sclerosis (MS) or rheumatoid arthritis, and identifies early, silent diseases. The methods involve testing of subject sera for the presence of epitope-specific serum IgE and also non-IgE antibodies. The tests are immunoassays wherein serum autoantibodies complex with peptides structurally mimicking humoral, autoimmune epitopes on, for example, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP) for MS. Each peptide: (1) is 5-6 amino acids long; (2) structurally and functionally mimics the surface region of its parent protein; and (3) offers a correct fit for the antigen binding site of a single specific autoantibody. Relapse prediction tests and therapies employ the peptides.