Dr. Sanna Goyert, armed with a PhD from New York University in 1983, proceeded to devote her laboratory in New York city to find a cure for sepsis, a severe immune reaction to a bacterial infection that was deadly if not intervened aggressively. In less than a decade, she discovered the human CD 14 gene and history was made! She has published over 100 research papers, holds 2 major patents licensed to companies finding cures, and has been awarded the prestigious Stohlman Scholars award from the Leukemia Society of America. Now, why would a scientist be rewarded by the Leukemia Society, after discovering the CD 14 gene and how might cells clear severe bacterial infection faster in the absence of the CD 14 gene? Why is the human CD 14 gene so important? That is the story I am attempting to tell here.
Paris hosted an international workshop in 1982 to classify the different types of white blood cells based on their cell surface molecules, which were named CD (Cell Differentiation). Today, in 2011 more than 320 CDs have been documented. The CD classification is often used to associate a cell with a certain immune function, and yet, only a few of them have been characterized. Generously funded research led to the discovery of the most notorious function of a white blood surface molecule, CD 4; it is the molecule to which the HIV (virus) binds, along with a second molecule, to gain entry into the human body. The important function of recognizing the sepsis bacterium by CD 14, came from research done in Dr Goyert’s lab.
The CD 14 molecule has been extensively researced for two decades. Although, CD 14 became less trendy, Dr Goyert remained devoted to the gene that she had discovered in 1988, and persisted in trying to understand how CD 14 gets a job done. Dr Hubertus Jersmann, of the University of Adelaide, Australia surmised that the CD 14 molecule is found in low amounts in many different cell type surfaces in addition to the white blood cells. Such cell types include the gingivis cells, the gut or intestinal cells, the islet cells of the pancreas and the spermatozoa. CD 14 is recognized as the first PAMP receptor discovered, where PAMP represents “Pathogen Associated Molecular Pattern”. In 1990, CD 14 was characterized as the PAMP receptor for bacterial endotoxin (LPS).
Most people today are aware of at least one child who is allergic to a certain type of food. This surprises many of the older generation when everybody ate everything without being “allergic”. It becomes impossible to complain about the inconvenience of accommodating a child or adult who might be allergic to the menu of choice. How do you continue to complain when a child with anaphylactic shock to peanuts or another food is rushed to the emergency room because of the menu? How do you not become more accommodating when you hear of a teenager dying from eating in a restaurant, assuming that the menu is “peanut free” or free of known allergens?
But why is this happening? Now, we are beginning to notice a pattern and there are three modes of action:
1) An immediate search for a cure;
2) An immediate need for policy to accommodate the increasing number of children, (and now teens and adults who were children a decade ago) who are allergic to a growing list of allergens;
3) A scientific race to find the culprit or environmental trigger or genetic markers or a combination of factors that may lead to food allergy; a race to find the genetic markers that protect an individual from an allergic reaction to the same combination of culprit factors.
Here, I will discuss the genetic markers that appear to increase or perhaps, decrease the risk of food allergy. We do not understand the role of these genetic markers or why they are selectively responding to an unknown factor or a combination of factors to produce an allergic reaction. I am absolutely certain that this genetic marker alone does not cause the child to become allergic. It is however, one of the factors and may hold clues to an environmental or another unknown trigger. It is also important to learn which genetic markers are protecting the non-allergic population from the same culprit triggers. This allergic reaction may range from mild to deadly. Please, alert me by commenting here if you hear of an update.
There are nine most common allergens known today and many less common or rare allergens. A good place to begin as a service provider or care giver to help understand an allergic child or adults is the 30 page educational guide published by the United States Department of Agriculture in “Food Allergy and Intolerance Resource List, December 2010“.
Why are some people allergic to egg? The 2011 to 2012 flu seasonal vaccine in the USA is manufactured only in eggs, although Europe has introduced egg – free vaccination. This denies most people in the world who are allergic to egg an opportunity to artificially protect themselves against the flu virus. In an earlier article, I have discussed the properties of the flu virus and the vaccines currently in development. According to the United States Department of Agriculture, egg allergy is one of the nine common allergens in 2010.
One gene that is being associated with allergy is the CD 14 gene. It is on chromosome 5 of humans in the 5q23-31 region. There are several interesting facts about this CD 14 gene. It has been cloned and the gene has two exons (protein coding regions). It has a membrane bound form called mCD 14 and a plasma shredded form called sCD 14. The sCD 14 level in plasma increases during inflammation (allergic reaction) and infection by a pathogen. The gene has several known polymorphisms (mutations) of which one, at position -159 of the promoter region that regulates the production of this gene, is of particular interest. Position -159 of CD 14 gene, is associated in some people with allergies. Position -159 together with -1619 correlated with a decrease in lung function when farmers with mutations of the CD 14 gene where exposed to endotoxin. Influence of genes and environment on allergic reactions has been reviewed by Dr. Kondo, a researcher in Japan, which unfortunately, I could not read, and researchers at University of Arizona. Dr Vercelli at Arizona says that it is the task of functional genomists to figure out what is the potential role of CD 14 in the progression of an allergic disease. He is of the opinion that the environment is likely to play an essential role.
The CD 14 gene plays a role in diseases other than allergy. The Alzheimer’s amyloid peptide binds to CD 14, implicating it in the disease progression of the aging microglia cells of the brain. In the Chinese population, a single base change in the CD 14 regulatory region of the gene (-260 C/T polymorphism) can contribute to a higher risk of getting Acute Lymphoblastic Leukemia. Level of mutated CD 14 (-260 T/T) in gingiva cells is associated with severe periodontal disease in Dutch. A polymorphism in CD 14 is associated with Crohn’s disease. In a South Korean population, patients with Tuberculosis were more likely to carry the CD 14 (-159 T/T) polymorphism. Turkish scientists have found elevated levels of CD 14 in Brucellosis, a bacterial disease. Elevated levels of CD 14 are found in tuberculosis. There was no obvious role of CD 14 in arthritis produced by the lyme bacterium in Germany.
How can you help in food allergy research? You can do it in several ways but the one that I would suggest that might make a major difference is if you can show the scientists working on this field that they are our heros. For a scientist, your encouragement is like the “wind beneath the wings”. For example, you could send Dr Sanna Goyert an email showing her you care about the impact her research has made towards allergy research. Her email: email@example.com. Write to influencers and request that Dr Goyert should be showered with awards. Please, note that this is a woman scientist. Then, find other scientists working on allergy and encourage them in your own unique way. Write to Dr Kondo (firstname.lastname@example.org) in Japan, Dr Hubertus Jersmann at the University of Adelaide, Australia, Dr M L Laine in Netherlands, and Dr Vercelli at University of Arizona and encourage them to find the role of CD 14 and the environmental trigger in allergy progression. You could also write to companies encouraging their scientists to find a cure. Your support counts to a dedicated allergy researcher. The technology exists today to solve this disease puzzle. Together, we can beat this modern scourge of allergy.