The aim of I3T (immunity, inflammation, infection and transplantation) researchers is to provide the big picture, the 35,000-foot view on what immunity is — and what constitutes a normal immune system.
Then, it will be possible to more accurately tweak the system, to boost it to fight cancer, for example, or to tamp it down to protect transplanted organs, or treat autoimmune diseases.
Current physical exams and tests, such as of blood and urine, do not tell physicians anything significant about the health of a person’s immune system — even though a rampant and chronic immune response might be destroying joints, tissue and organs or that a weak, ineffectual immune system may be permitting recurrent infections to flourish or cancer to grow.
UCLA scientists have a vision that, in addition to running standard tests like checking blood pressure and cholesterol levels during a wellness check-up, your primary care physician would also perform:
If you become ill later on, the same tests, but with more detail, would be used by your physician to establish what has changed since your baseline test.
The comprehensive diagnostic of your blood-based immune system will point out strengths and weaknesses in specific immune factors that are protecting you against development of many common disorders. This is the essence of preventative medicine.
This test would help you:
Your gut microbiome is the five pounds of more than 100 trillion bacteria cells that inhabit your colon. It contains its own immune system in order to control the day-to-day dynamics of what physicians collectively refer to as the “florid” microbiome. A healthy microbiome floats all immune system boats.
The differing types of bacteria work symbiotically:
Results of the microbiome test will highlight any need for corrective bacteria. You will leave the doctor’s office not only with a statin prescription for your cholesterol, but also a cocktail of immune system boosters tailored to you, as well as a script for gut biota.
UCLA scientists say this vision highlights a new understanding of human health. The immune system is a player in— if not the cause of— many human diseases. Possibly aging, too.
Yet, so little is really known about the immune system or its powerful ally, inflammation. Inflammation is activated by threats like:
Inflammation also signals an appropriate immune response. Many disorders, such as rheumatoid arthritis, are associated with chronic, uncontrolled inflammation, and UCLA researchers are working on ways to suppress the harmful aspects of inflammation without affecting the immune system’s role in fighting infection.
Autism also appears to have connections to microbiota and immune dysregulation. In fact, UCLA researcher Dr. Elaine Hsiao has found that mice with autistic-like behavior also have abnormal microbiomes and autism-related immune and gastrointestinal problems. These findings suggested that treating co-morbid microbiome, immune and gut issues could influence the main behavioral symptoms of autism.
Dr. Hsiao also found in mouse models of autism a gut bacterium (Bacteroides fragilis) that significantly reduced autistic-like behaviors in the animals. She said researchers are beginning to understand how microbes in our guts can alter behavior — and that raises the exciting prospect of identifying new targets for therapeutic intervention.
UCLA researchers want to know if there are different types of “normal” when it comes to immunity. If there are, that means each of them has unique resistances and susceptibilities to immunologic problems.
That’s why UCLA scientist Dr. Jonathan Braun wants to create what he calls a “dashboard of human immunity” to provide a picture of what normal immunity looks like. He says the answer could be “crowdsourced” by mining the massive amounts of de-identified data readily available thanks to the thousands of individuals seen at UCLA sites. The source researchers would use would be the results of standard blood tests, de-identified to protect patient privacy.
Knowing a person’s unique biological profile is necessary for the coming era of precision medicine, he says. The dashboard concept will help UCLA researchers identify the best treatment available for each patient — an overarching mission of the David Geffen School of Medicine at UCLA.
Dr. Braun is already helping to build a comprehensive dashboard on intestinal microbiome by crowdsourcing. The composition of each person's microbiome is very different, because of the types of bacteria people ingest early in their lives, as well as the effects of daily diet, lifestyle and genetics.
As part of a $10 million grant from the Crohn’s & Colitis Foundation of America, he is working with “citizen scientists” who have inflammatory bowel disease and who have offered to send in small samples of their stool for analysis — the source offered by a crowd that will total 20,000 people across the country. Dr. Braun says the findings, compared to healthy microbiomes, will reveal the metabolites (the products made by bacteria) that are contributing to bowel disease.
Most of the interior of the body is sterile, but other microbiome “communities” exist in addition to that in the gastrointestinal tract — on and in the skin, around the eyes and the oral mucosa. All have an impact on health, he says.
“You depend on your auto’s dashboard to help you operate your car. Pilots couldn't fly without their dashboard controls,” Dr. Braun says. “As physicians, we need all the information we can get from a medical dashboard in order to provide the precision medicine we are all working toward.”
If doctors had a profile of every individual’s normal immune system, then predictions could be made based on weaknesses in the system and a person’s genes, and if they’re susceptible to any disorders.
But on a macro-level, aggregated profiles could paint a picture of which immune factors are normal and healthy across ages, races, ethnicities and genders. Using these profiles, a family doctor could use a blood test to tell a patient what may be off, and worth further testing and treatment.
Dr. Elaine Reed, professor of pathology and director of the UCLA Immunogenetics Center, is creating several immunity-based models designed to predict health outcomes. In collaboration with researchers at UCLA’s heart failure program, she is developing a test that characterizes different subsets of immune cells in the blood of patients with heart failure. The goal is to predict which patients are going to develop multi-organ failure, and so far, the team has found certain populations of cells (such as molecules that activate or suppress immunity) that expand in advance of organ dysfunction. This, she says, is the crux of precision medicine.
These tests can be custom-developed for use across all disease states. “We are figuring out how immune factors relate to different disease states, and how to use a dashboard to predict those diseases and hopefully prevent them,” Dr. Reed says.