For as long as I’ve been in neurology (since 1967) we’ve known that multiple sclerosis (MS) has something to do with the immune system Oligoclonal bands of Immunoglobulin G (antibodies to you) were found in the spinal fluid of MS patients in 1960. Oligoclonal means that the antibodies were reacting to a few antigens. 58 years later just what they are reacting to “remains unclear” [ Neuron vol. 97 p. 750 ’18 ].
Spinal taps to get CSF to look for them have long been replaced by Magnetic Resonance Imaging (MRI). To show you just how primitive neurology was when I started (long before Computerized Axial Tomography scans (CAT scans) or MRIs, consider the hot bath test. MS is many things, but an attack on myelin (the fatty cover of nerve fibers) is one of them. This makes the nerve fibers (axons) conduct impulses more slowly, where myelin is diseased. The impulses get messed up in time the same way vinyl played at the wrong speed isn’t music. Heating nerve fibers exaggerates the conduction deficits, and up NYC under Morris Bender, people were given neurologic exams than put in a hot bath and examined again to look for new neurologic signs.
Back then we could only measure MS activity by clinical examination, looking for new neurologic problems or worsening of old ones. MRIs changed all that, showing us for the first time lesions in the white matter where MS was attacking myelin (which is basically fat and what makes white matter white). MS is far more active than the appearance/disappearance of neurologic signs can tell us.
Prior to MRI, neurologists were like hematologists having to treat leukemia or anemia by looking at the patient’s color and unable to get a blood count to see what was going on.
MS has been under intense study and long before I started in neurology.
Animal models (Experimental Allergic Encephalomyelitis (EAE), etc. etc.) are made by immunizing animals with the proteins of myelin. One such protein is myelin basic protein (MBP) accounting for about 1/3 of all myelin proteins (myelin isn’t pure fat, but it’s close). EAE is produced by immunizing animals with MBP.
The new wrinkle is hot off the presses to start the new year [ Nature vol,. 637 pp. 41 – 42, 176 – 183 ’25 ]. The class II Major Histocompatibility Complex Class II proteins (MHC-II) are what presents protein fragments to the immune system. Using very delicate analytic chemistry techniques, it is possible to find out just what these fragments are (in normal people), and the new wrinkle is that some of them are fragments of MBP itself which has 175 amino acids (actually amino acids #160 – #175).
So they gave these two fragment of MBP to two animal models of EAE, and it made the disease better. The authors call these fragments guardian peptides.
People have been debating for years whether infections trigger MS clinical attacks (as opposed to asymptomatic worsening of MRI scans). I haven’t kept up enough with the literature to know if this has been resolved.
But if clinical attacks are produced by infection (not the chronic disease itself which is a whole other story), the paper provides a mechanism by which this might happen.
Instead of presenting guardian peptides MHC-IIs are presenting peptide fragments of the invading organism, and MS gets worse, and a clinical attack begins.
Interesting isn’t it.
