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Polyneuritis equi is an overlooked disease Part 2

tangle-of-nervesThe disease progression of polyneuritis equi (PE) includes an immunological response to an infection or allergic neuritis (in response to proteins released by trauma or infection).  The initial infection stimulates harmful responses that persist after the infection resolves and is no longer detected.  Damage is to the myelin covering nerves, specifically the P2 protein. A similar disease in people is Guillain-Barre syndrome.

A French physician described a variant of Guillain-Barre called Landry’s paralysis in 1859.  Landry described a wider group of peripheral neuropathies.  Polyneuritis equi may be similar to Landry’s paralysis. Most of the research in human neurological disease that depended on spinal tissue began to get material from horses when Mad Cow disease hit Europe.  The scientists didn’t want to continue to use nerve tissue from European cows.

We define polyneuritis equi by the presence of anti-myelin protein antibodies in serum of horses showing neurological disease.  Six published references link serum antibodies to anti-P2 protein with clinical signs in horses. There is also useful unpublished data. One researcher at CA Davis attempted to develop a P2 ELISA but failed to get a relationship between several cases and a positive ELISA test.  Another clinician at OSU tried to produce experimental polyneuritis equi by injecting P2 into a few horses, but his model failed. Why can we detect antibodies in serum when others didn’t make the connection? The negative data from these scientists are explained by the processes that produce disease. This is a boon for our work.

An antecedent infection sets off a harmful immune reaction.  The nerves are repaired by remyelination, but sometimes the process begins a damage/repair cycle. The repair process deposits microscopic calcium on the damaged nerve, calcification is a common result of chronic inflammation.  At this point the disease is terminal in horses. The disease is called cauda equina neuropathy (CEN) and is characterized by recognizable histological lesions that are a progressive granulomatous inflammation of peripheral nerves. CEN is chronic and has an apparent predisposition for involving the extradural nerve roots of the cauda equina.

There is an experimental model that was developed in rats. Rats are given P2 protein injections that results in EAN (experimental allergic neuritis). EAN can be induced in other animals. Rat-EAN can be induced by peripheral nerve myelin, myelin basic proteins, P2 protein, or small pieces of P2 protein, Neuritogenic Peptides. There is a positive correlation between the severity of the clinical signs and the dose of Neuritogenic Peptides from P2.  The disease in rats is characterized by demyelination of the roots of sacral and sciatic nerves given “high” doses of P2.

There is mild disease accompanied by mild signs in 40% of a low dose, P2-immunized group.  Neither group showed signs attributed to the central nervous system indicating the disease involves the peripheral nerves.  And ponder this, repeated stimulation using the P2 antigen resulted in refractory disease, the rats stopped getting sick! Compare that with results when giving repeated doses of the Neuritogenic Peptide—rats continued to suffer disease.

In a field case antibody is made anywhere on myelin protein.  If there is continued damage to one area of a nerve and on a smaller scale, the myelin P2 protein, then anti-P2 antibodies are produced.  These antibodies are measured by ELISA.  After several rounds of the inflammatory cycle it is probable that the nerves calcify.  Its possible that is the refractory stage of disease and no antibody is made, the damage is now due to the calcified nerves.  However, in disease many areas of P2 elicit antibody production and that includes the Neuritogenic Peptide.  The rat studies indicate there will be no refractory period and antibodies will continue to be measureable against the this peptide.

Based on these data we developed our ELISA to measure both P2 and the Neuritogenic Peptide, hopefully to gain enough data to stage the disease process.  The CA Davis team didn’t look at the neuritogenic peptide in their assay and, in late disease, it is probable P2 antibody wasn’t present.  In the OSU experimental model it would be expected that 40% of the horses would show mild disease; it would take at least 20 animals to come up with definitive disease using whole P2 protein.  However, if the Neuritogenic Peptide was employed, all the animals could be expected to show signs and measurable antibodies.

Why do horses get this disease?  You have to look at the structure of myelin P2 protein to understand and treat polyneuritis equi.