Anti-myelin basic protein and anti-proteolipid protein specific forms of multiple sclerosis

Human myelin basic protein (hMBP) and proteolipid protein (PLP) were used as antigens in a solid‐phase radioimmunoassay to determine relative frequencies of anti‐MBP and anti‐PLP in cerebrospinal fluid (CSF) of optic neuritis and multiple sclerosis (MS) patients. Forty‐nine of 55 patients with optic neuritis had increased CSF anti‐MBP and the remaining 6 had increased anti‐PLP. Of 385 MS patients, MS relapse: 173 of 180 patients had increased anti‐MBP, 5 of the remaining 7 patients had elevated anti‐PLP, and 2 had neither of these autoantibodies. Progressive MS: 111 of 116 patients had increased anti‐MBP in either free and/or bound form, of the remaining 5 patients 4 had increased anti‐PLP, and 1 had neither anti‐MBP nor anti‐PLP. MS remission: 15 of 87 patients had somewhat increased anti‐MBP, none had anti‐PLP. IgG was purified by affinity chromatography from necropsy central nervous system (CNS) tissue samples of 4 individual patients with clinically definite and neuropathologically confirmed MS. Three of these 4 patients who had increased levels of CSF anti‐MBP also had increased anti‐MBP titers in CNS tissue‐extracted IgG. The fourth patient who had anti‐PLP in CSF also had anti‐PLP in brain tissue IgG. These autoantibodies were not detected simultaneously in any patient. These results suggest that there are at least two immunologically distinct forms of MS, i.e., a common form highly associated with anti‐MBP and more frequent prominent inflammatory characteristics in CSF and CNS, and an infrequent form associated with anti‐PLP in CSF and tissue, and less abundant inflammation. Anti‐MBP purified from CNS tissue IgG by antigen‐specific affinity chromatography was reacted with synthetic peptides of hMBP. The anti‐MBP epitope on the hMBP molecule was restricted between residues 75 and 106. The PLP epitope for anti‐PLP has not as yet been determined. These observations have theoretical implications for anticipated future specific immunotherapy of MS.