Why do some people develop reactions in response to immune system challenges while others don’t?

This week, in a study published in the New England Journal of Medicine, Dr. Thomas Platts-Mills of the University of Virginia and colleagues looked at reports of patients who experienced what they believe are severe allergic reactions to the cancer drug Erbitux. The drug, which is widely used — it had global sales of $1.1 billion in 2006 for use in treating colon, head and neck cancers — is a monoclonal antibody, a genetically engineered immune system compound designed to home in specifically on cancer cells.

The team tested 538 people, including 76 cancer patients who got Erbitux in Tennessee, Arkansas and North Carolina and healthy volunteers from Tennessee, California and Boston in order to gauge their reaction to the drug. Of the 76 cancer patients, 25 developed what were labelled “hypersensitivity reactions.”

Data revealed that the number of patients to develop a reaction to Erbitux varied depending on location. Platts- Mills and team found that as 22 percent of patients treated with Erbitux in Tennessee and North Carolina reported some kind of reaction, including anaphylaxis, which can rapidly lead to difficulty breathing, shock or fainting. Some of the reactions were described as life threatening. Even higher rates were reported from parts of Arkansas, Missouri and Virginia. But fewer than 1 percent of patients treated in the Northeast reported any reactions.

Unable to explain their results, the research team realized that ticks and other insects are more common in the states in which patients negatively react to Erbitux at higher rates. Although the team hypothesized that tick bites might generate antibodies that could cause an “allergic reaction” to Erbitux, a more likely explanation is that patients who get enough tick and other insect bites harbor greater numbers of the Th1 pathogens.

Contrary to mainstream thinking, ticks and other insects are able to transmit many more bacterial species then simply Borellia. Thus, people who get tick bites are more likely to accumulate a variety of Th1 pathogens – bacteria that proceed to create ligands that block the Vitamin D Receptor and subsequently the activity of the innate immune system.

Of the many people who are bitten by ticks on a daily basis, only a fraction of people report a bite that causes them to develop a rash and an array of debilitating symptoms usually labelled as Lyme disease. According to biomedical researcher Trevor Marshall, it is the state of the innate immune system that determines whether people who are frequently exposed to ticks develop such a reaction after a bite.

“Most people who are bitten by ticks don’t even realize it,” states Marshall. But a portion of the people bitten by a tick have already accumulated enough Th1 pathogens so that their innate immune systems are simply unable to deal with the new influx of pathogens from the bite. These are the people who develop a rash and become symptomatic after an insect bite – they are already immunocompromised, and their symptoms are an indication of the fact that their innate immune systems have lost the ability to deal with a new invading pathogen.”

Could this same phenomenon explain why those people who live in states with greater insect populations are more likely to develop a reaction to Erbitux? If a person accumulates enough L-form bacteria due to numerous insect bites, their innate immune system becomes increasingly impaired. If they proceed to develop cancer – a disease that also begins to destroy innate immune function – would those individuals with previously weakened innate immune systems find it much harder to handle the antibody introduced by Erbitux, leading to an immune reaction?

Sure, further research must be conducted to determine exactly how Erbitux might react with cancer causing bacteria in a way that causes immunocompromised people to develop such violent symptoms. But it seems logical that the state of the innate immune system is what determines whether or not a patient can tolerate the Erbitux antibody.

Will further research be done? Probably not in the near future, as mainstream researchers would be hard pressed to believe that such a great proportion of the population is infected with such high quantities of the Th1 pathogens, or that these bacteria affect the pathogenesis of cancer. Still, those of us who know how rampant the Th1 pathogens are can take a good look at this research and see that unfortunately, it confirms just how drastically their effects on the immune system impact all areas of medicine.[1]

REFERENCES

  1. Chung, Christine H et al. 2008. “Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose.” The New England journal of medicine 358(11):1109-17. []