The requirement of ammonium or other cations linked with p-cresol sulfate for cross-reactivity with a peptide of myelin basic protein.
Urinary myelin basic protein-like material (MBPLM), so designated because of its immunoreactivity with a polyclonal antibody directed against a cryptic epitope located in residues 83-89 of myelin basic protein (MBP), exists in humans normally but increases in concentration in patients with multiple sclerosis who have progressive disease. Given its possible role in reflecting events of neural tissue destruction occurring in multiple sclerosis, urinary MBPLM is a candidate surrogate marker for this phase of the disease. Previously, it has been demonstrated that p-cresol sulfate (PCS) is the dominant component of MBPLM; however, another component(s) was essential in enabling p-cresol sulfate to have molecular mimicry with MBP peptide 83-89 detected by immunoreactivity. In the present investigation, this remaining component(s) was characterized by a combination of high performance size exclusion chromatography followed by nuclear magnetic resonance spectroscopy and shown to be ammonium. The monovalent cation ammonium could be substituted in vitro by several different monovalent and divalent cations, most notably zinc, in restoring to deprotonated p-cresol sulfate its immunoreactivity as MBPLM. These findings indicate the basis for the unexpected molecular mimicry between an epitope of an encephalitogenic protein and a complex containing a small organic molecule, p-cresol sulfate. Furthermore, the reaction of either ammonium or other cations with p-cresol sulfate may represent an in vivo process directly related to damage of axonal membranes.
Jackson
Patricia L
PL
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cao
Ligong
L
Blalock
J Edwin
JE
Whitaker
John N
JN
D002412:Cations / Q000737:chemistry; D002850:Chromatography, Gel; D003408:Cresols / Q000032:analysis / Q000737:chemistry* / Q000276:immunology / Q000652:urine*; D003429:Cross Reactions; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000276:immunology / Q000652:urine*; D010455:Peptides / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000032:analysis / Q000737:chemistry* / Q000276:immunology / Q000652:urine*; D014556:Urine / Q000737:chemistry*
D002412:Cations; D003408:Cresols; D004676:Myelin Basic Protein; D010455:Peptides; D000644:Quaternary Ammonium Compounds; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate