The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis

A polyclonal antiserum has been produced that can detect nanogram amounts of myelin basic protein (MBP)-like material in unconcentrated human urine. The urinary immunoreactive material is cross-reactive with human MBP peptides 45-89 and 69-89, dialyzable, heat resistant, and is not artifact of either degradation of radioligand or salt effect. An octapeptide, MBP peptide 82-89, was demonstrated to be the smallest peptide containing the main epitope against which this antiserum was directed. This epitope differed from the major epitope recognized by antisera detecting MBP-like material in cerebrospinal fluid, implying that the MBP-like material is altered, presumably degraded, in the kidney. Results of gel filtration and high-performance liquid chromatography suggested a size of 1,000 daltons or less and a charge similar to that of human MBP peptide 80-89. In a group of 39 persons with multiple sclerosis, 48 with other neurological diseases, and 26 normal control subjects, the concentration of urinary MBP-like material, related to the concentration of urinary creatinine, was significantly higher in the multiple sclerosis group (22.0 ng MBP-like material/mg creatinine) than in the other neurological diseases or control groups, in which the values were 7.0 and 3.9 ng MBP-like material/mg creatinine, respectively. Variations in the level of MBP-like material appearing in the urine may provide a clinically feasible test for myelin damage. The precise identification of the chemical nature of the urinary MBP-like material may also furnish a means for further analyzing the in vivo catabolism of the potentially autoantigenic MBP.