ANTIMYELIN BASIC-PROTEIN AND ANTI-PROTEOLIPID PROTEIN-SPECIFIC FORMS OF MULTIPLE-SCLEROSIS

Human myelin basic protein (hMBP) and proteolipid protein (PLP) were u sed as antigens in a solid-phase radioimmunoassay to determine relativ e 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 remai ning 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. Progres sive 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 patien ts had somewhat increased anti-MBP, none had anti-PLP. IgG was purifie d 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 i ncreased 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 a lso had anti-PLP in brain tissue IgG. These autoantibodies were not de tected 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 infl ammatory characteristics in CSF and CNS, and an infrequent form associ ated with anti-PLP in CSF and tissue, and less abundant inflammation. Anti-MBP purified from CNS tissue IgG by antigen-specific affinity chr omatography was reacted with synthetic peptides of hMBP. The anti-MBP epitope on the hMBP molecule was restricted between residues 75 and 10 6. The PLP epitope for anti-PLP has not as yet been determined. These observations have theoretical implications for anticipated future spec ific immunotherapy of MS.