A Brief History of MAP and Crohn’s
For the last 20 years, a dedicated group of Doctors and Researchers have been studying the pathogen Mycobacterium avium ssp paratuberculosis and its relationship to Crohn’s disease and other diseases termed “autoimmune” diseases. For years, the prevailing view was that IBD was an autoimmune disease, which meant that the patient’s body was attacking itself due to some type of an imune system misfire. However, a self-antigen has never been found. Antigens are substances, like proteins, that are present on cells to alert the immune system to a foreign invader. They stimulate an immune response and the body recognises and destroys the invader. A simplistic example would be to imagine a group of soldiers all wearing red coats who represent the cells of the immune system. When a foreign invader with a blue coat turns up, they know to attack. An autoimmune disease is when the cells of the immune system (in our example the red coats) engage in a civil war. It was believed that the immune system in Crohn’s disease patients was in essence engaged in a civil war, but new research has moved away from that theory.
The latest research suggests that Crohn’s disease is more correctly classified as an immune mediated disease, with contributing genetic and environmental components. This means that the immune system is reacting to something in the gut. The researchers who participated in the Chicago Symposium believe that many Crohn’s disease patients have a genetically altered immune system which does not allow their macrophages (a type of white blood cell) to correctly recognize and rid the body of the Mycobacterium species known as MAP. Instead, MAP invades the macrophages by shedding it’s cell wall and setting up permanent residence. Due to genetic mutations (like those found in the NOD2, ATG16L1 and IRGM regions) the autophagy response that destroys the invaded cells is impaired, and MAP is allowed to remain and multiply. Returning to our red coat/blue coat example, it’s as if the red coated cells have developed red/blue color blindness, and can only see the blue coated cells as red, although this is greatly simplifying the issue.
MAP was first identified as a pathogen in the late 1800s, where it was causative of Johne’s (pronounced YO-nees) disease in cattle. Johne’s disease is eerily similar to Crohn’s disease in both symptoms and histology. The cattle became very sick, had diarrhea and lost weight. It was highly infectious via milk, water and manure and generally fatal. In 1895, MAP was identified as the cause of Johne’s disease, though no one could explain how an animal infected by the MAP organism early in life would not show symptoms of the disease until much later. They knew that at some point, the MAP started to replicate and when the immune system responded, granulomatous inflammation was the result. Over time, this inflammation prevented the intestine from absorbing nutrients. Eventually, the animal starved despite eating a healthy diet.
Today, Johne’s disease has been found in every country that has tested their animals. It’s estimated that almost 70% of United States dairy herds have at least one animal with Johne’s disease. Dr. Michael T. Collins is one of the world’s foremost experts on Johne’s disease. His site, the Johne’s Disease Information Center, provides detailed information and resources for those wanting more information about Johne’s disease. The Paratuberculosis Awareness and Research Association also gives detailed information and up to date information surrounding this subject.
The connection between MAP and Crohn’s disease was first studied over 100 years ago. In 1913, Dalziel noted similarities in the intestines of sick humans and cattle suffering from Johne’s disease. He proposed that Johne’s disease and what would become Crohn’s disease were the same. Fast forward to 1932 and the discovery of Crohn’s disease. Strikingly similar symptoms and the characteristic granulomatous inflammation associated with Johne’s disease began to show up in increasing numbers in the human population. The disease became known as Crohn’s disease after Dr. Burrell B. Crohn. There is currently no accepted cause of Crohn’s disease, though some leaders in the field postulate that a Mycobaterium species plays more than a bystander’s role.
What Role Does MAP Play in Crohn’s Disease?
Studies have shown that the MAP (or a very similar Mycobacterium species) is present in a higher percentage of Crohn’s patients than the general population. When most people are exposed to MAP through the food chain or environment, their immune systems contain it and they don’t get sick. However, some people have genetic factors which hinder their immune systems from fighting off MAP. A group of researchers believe that a Mycobacterium species may play a key role in other immune-mediated conditions like Type I diabetes, multiple sclerosis and rheumatoid arthritis as well.
In a subset of Crohn’s patients whose immune system does not respond adequately to prevent intracellular bacterial infection due to genetic susceptibility, there is evidence to suggest that MAP may play a triggering role. (For more detailed information, see this article.) The result for these genetically susceptible people is Crohn’s disease.
Recently, John Aitken and his New Zealand team, in collaboration with a group in Europe, have discovered new methods to culture MAP related bacteria. Being able to accurately detect MAP or related Mycobacterial species in the human population is critical, but not readily available. One species of Mycobacteria that John’s New Zealand lab grew from patients with Crohn’s disease appeared similar to MAP, but not the same, and was thus nicknamed “Son of MAP.” Regardless of the name, Crohn’s disease patients could be distinguished from non-Crohn’s patients by looking for the presence of Son of MAP. The hypothesis is that Son of MAP is a cell-wall-deficient Mycobacteria which plays a triggering role in Crohn’s disease. However, more research is needed and is ongoing. For a more complete explanation of Son of MAP and the role it plays in Crohn’s disease, please see Mr. Aitken’s informative presentation.