p-Cresol sulfate is the dominant component of urinary myelin basic protein like material.
Multiple sclerosis (MS) is clinically heterogeneous and has an uncertain natural history. A high priority for more effective treatment of MS is an objective and feasible laboratory test for predicting the disease's course and response to treatments. Urinary myelin basic protein (MBP)-like material (MBPLM), so designated because it is immunoreactive as a cryptic epitope in peptide 83-89 of the human MBP molecule of 170 amino acids, is present in normal adults, remains normal in relapsing-remitting, but increases in progressive MS. In the present investigation, MBPLM was purified from urine and characterized. p-Cresol sulfate is the major component of urinary MBPLM. This conclusion is based on the following: (1) MBPLM and p-cresol sulfate both have a mass of 187 on negative scans by electrospray ionization mass spectrometry, the same fragments on tandem mass spectrometry of 80 (SO(-)(3)) and 107 (methylphenol), and similar profiles on multiple reaction monitoring; (2) (1)H and (13)C nuclear magnetic resonance spectroscopy revealed identical spectra for MBPLM and p-cresol sulfate; (3) purified p-cresol sulfate reacted in parallel with MBP peptide 83-89 in the same radioimmunoassay for MBPLM; and (4) p-cresol sulfate has the same behavior on preparative HPLC columns as urinary MBPLM. The unexpected immunochemical degeneracy permitting a cross-reaction between p-cresol sulfate and a peptide of an encephalitogenic myelin protein is postulated to be based on shared conformational features. The mechanisms by which urinary p-cresol sulfate, possibly derived from tyrosine-SO(4), reflects progressive worsening that is disabling in MS are unknown.
Cao
L
L
Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35233-7340, USA.
Kirk
M C
MC
Coward
L U
LU
Jackson
P
P
Whitaker
J N
JN
D019342:Acetic Acid / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D064753:Ammonium Hydroxide; D002851:Chromatography, High Pressure Liquid; D003408:Cresols / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000652:urine*; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008970:Molecular Weight; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology / Q000652:urine; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification / Q000652:urine*; D011108:Polymers / Q000378:metabolism; D011863:Radioimmunoassay; D020539:Sequence Analysis, Protein; D013431:Sulfates / Q000032:analysis; D013463:Sulfuric Acid Esters / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000652:urine*; D019789:Tetraethylammonium / Q000378:metabolism
D000596:Amino Acids; D003408:Cresols; D000939:Epitopes; D006878:Hydroxides; D004676:Myelin Basic Protein; D011108:Polymers; D013431:Sulfates; D013463:Sulfuric Acid Esters; C032538:4-cresol; D064753:Ammonium Hydroxide; C408690:4-cresol sulfate; D019789:Tetraethylammonium; D019342:Acetic Acid