Findings reveal further detail about protein linked to inflammatory disorders
It was nine years ago that University of Maryland School of Medicine researchers discovered that a mysterious human protein called zonulin played a critical role in celiac disease and other autoimmune disorders, such as multiple sclerosis and diabetes. Now, scientists have solved the mystery of zonulin's identity, putting a face to the name, in a sense. Scientists led by Alessio Fasano, M.D., have identified zonulin as a molecule in the human body called haptoglobin 2 precursor.
Pinpointing the precise molecule that makes up the mysterious protein will enable a more detailed and thorough study of zonulin and its relationship to a series of inflammatory disorders. The discovery was reported in a new study by Dr. Fasano, published the week of September 7, 2009 in the online version of the Proceedings of the National Academy of Sciences. Dr. Fasano is a professor of pediatrics, medicine and physiology and director of the Mucosal Biology Research Center and the Center for Celiac Research at the University of Maryland School of Medicine.
Haptoglobin is a molecule that has been known to scientists for many years. It was identified as a marker of inflammation in the body. Haptoglobin 1 is the original form of the haptoglobin molecule, and scientists believe it evolved 800 million years ago. Haptoglobin 2 is a permutation found only in humans. It's believed the mutation occurred in India about 2 million years ago, spreading gradually among increasing numbers of people throughout the world.
Dr. Fasano's study revealed that zonulin is the precursor molecule for haptoglobin 2 - that is, it is an immature molecule that matures into haptoglobin 2. It was previously believed that such precursor molecules served no purpose in the body other than to mature into the molecules they were destined to become. But Dr. Fasano's study identifies precursor haptoglobin 2 as the first precursor molecule that serves another function entirely - opening a gateway in the gut, or intestines, to let gluten in. People with celiac disease suffer from a sensitivity to gluten.
"While apes, monkeys and chimpanzees do not have haptoglobin 2, 80 percent of human beings have it," says Dr. Fasano. "Apes, monkeys and chimpanzees rarely develop autoimmune disorders. Human beings suffer from more than 70 different kinds of such conditions. We believe the presence of this pre-haptoglobin 2 is responsible for this difference between species."
"This molecule could be a critical missing piece of the puzzle to lead to a treatment for celiac disease, other autoimmune disorders and allergies and even cancer, all of which are related to an exaggerated production of zonulin/pre-haptoglobin 2 and to the loss of the protective barrier of cells lining the gut and other areas of the body, like the blood brain barrier," says Dr. Fasano.