Perception of self: distinguishing autoimmunity from autoinflammation

Rheumatic diseases can be divided in two groups, autoinflammatory and autoimmune disorders. The clinical presentation of both types of diseases overlap, but the pathological pathways underlying rheumatic autoinflammation and autoimmunity are distinct and are the subject of ongoing research. There are a number of ways in which these groups of diseases differ in terms of disease mechanisms and therapeutic responses. First, autoinflammatory diseases are driven by endogenous danger signals, metabolic mediators and cytokines, whereas autoimmunity involves the activation of T and B cells, the latter requiring V-(D)-J recombination of receptor-chain gene segments for maturation. Second, the efficacy of biologic agents directed against proinflammatory cytokines (for example IL-1β and TNF) also highlights differences between autoinflammatory and autoimmune processes. Finally, whereas autoinflammatory diseases are mostly driven by inflammasome-induced IL-1β and IL-18 production, autoimmune diseases are associated with type I interferon (IFN) signatures in blood. In this Review, we provide an overview of the monocyte intracellular pathways that drive autoinflammation and autoimmunity. We convey recent findings on how the type I IFN pathway can modulate IL-1β signalling (and vice versa), and discuss why IL-1β-mediated autoinflammatory diseases do not perpetuate into autoimmunity. The origins of intracellular autoantigens in autoimmune disorders are also discussed. Finally, we suggest how new mechanistic knowledge of autoinflammatory and autoimmune diseases might help improve treatment strategies to benefit patient care.

Scientists discover how to ‘switch off’ autoimmune diseases

Scientists have made an important breakthrough in the fight against debilitating autoimmune diseases such as multiple sclerosis by revealing how to stop cells attacking healthy body tissue.

Rather than the body’s destroying its own tissue by mistake, researchers at the University of Bristol have discovered how cells convert from being aggressive to actually protecting against disease.

The study, funded by the Wellcome Trust, is published today [03 September] in Nature Communications.

It’s hoped this latest insight will lead to the widespread use of antigen-specific immunotherapy as a treatment for many, including (MS), type 1 diabetes, Graves’ disease and (SLE).

MS alone affects around 100,000 people in the UK and 2.5 million people worldwide.

Scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body’s own tissues while converting them into cells capable of protecting against disease.

This type of conversion has been previously applied to allergies, known as ‘allergic desensitisation’, but its application to has only been appreciated recently.

The Bristol group has now revealed how the administration of fragments of the proteins that are normally the target for attack leads to correction of the .

Most importantly, their work reveals that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.

In order to figure out how this type of immunotherapy works, the scientists delved inside the themselves to see which genes and proteins were turned on or off by the treatment.

They found changes in gene expression that help explain how effective treatment leads to conversion of aggressor into protector cells. The outcome is to reinstate self-tolerance whereby an individual’s immune system ignores its own tissues while remaining fully armed to protect against infection.

By specifically targeting the cells at fault, this immunotherapeutic approach avoids the need for the immune suppressive drugs associated with unacceptable side effects such as infections, development of tumours and disruption of natural regulatory mechanisms.

Professor David Wraith, who led the research, said: “Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure. These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat.”

This treatment approach, which could improve the lives of millions of people worldwide, is currently undergoing clinical development through biotechnology company Apitope, a spin-out from the University of Bristol.

How Conventional Medicine Got Autoimmune Diseases All Wrong.

I believe conventional medicine has it all wrong when it comes to treating autoimmune conditions. Autoimmune conditions affect over 50 million Americans, a large percentage of whom are women. Autoimmune diseases are now the third leading chronic disease in the country right behind heart disease and cancer. They are a top ten leading cause of death in women under the age of 65, and they come in more than 80 different varieties, including rheumatoid arthritis, type I diabetes, Lupus, thyroid disease, psoriasis, multiple sclerosis, and more. Yet, it takes an average of six-to-ten doctors and five years to receive one of these autoimmune diagnoses. What is conventional medicine doing wrong?

Autoimmune Disease: A Disease Of The Immune System

Under our current medical system, autoimmune diseases are not recognized as diseases of the immune system as a whole. Instead they are seen as diseases of particular organs. Unfortunately, that means that there isn’t a unified branch in conventional medicine to treat autoimmune conditions. With cancer for example, we have cancer specialists called oncologists who treat many different types of cancers no matter which organ system they involve. Yes, there are some subspecialties within oncology, but they typically still fall under one main oncology umbrella.

If, on the other hand, you are suffering from an autoimmune disease, you will see a specialist who focuses on the organ system that is being affected: a rheumatologist for rheumatoid arthritis; an endocrinologist for Hashimoto’s and diabetes, a gastroenterologist for celiac, ulcerative colitis and Crohn’s; a dermatologist for psoriasis; and so on. If you have multiple autoimmune conditions, as many people do, you will see several different specialists.

Supporting, Rather Than Suppressing, The Immune System

In conventional medicine, the belief is that once you have an autoimmune condition, there’s nothing you can do to reverse it, only ways to manage the symptoms. Managing the symptoms typically involves harsh medications that are aimed at suppressing your immune system. While these medications can be effective at reducing some of the symptoms of the disease, since they suppress the entire immune system, they aren’t without many unwanted side effects such as fatigue, weight gain, depression, increased infection rates and even cancer.

In contrast, functional medicine sees the body as a whole and works on the principle that the health of one system impacts the health and function of the others. Instead of focusing on disease symptom management, we focus on supporting and strengthening the immune system by getting to the root of why the immune system went rogue in the first place. While there is no known cure for autoimmune disease, I believe that there are five key elements that are at the root of all autoimmune conditions. In my functional medicine practice I have been able to successfully help hundreds of patients lower and reverse antibodies, get off their harsh medications, and become symptom free.

5 Underlying Causes of Autoimmune Disease

1. Gluten Intolerance

Gluten has been linked to more than 55 diseases and is damaging to the gut, causing symptoms that are not always digestive in nature but rather neurological such as pain, cognitive impairment, sleep disturbances, behavioral issues, fatigue and depression — a vague collection of symptoms present in many autoimmune conditions.

2. Leaky Gut

In order to absorb nutrients, the gut is somewhat permeable to very small molecules. Many things including gluten, infections, medications and stress can damage the gut, allowing toxins, microbes and undigested food particles — among other things — directly into your bloodstream. Leaky gut is the gateway for these infections, toxins, and foods like gluten to begin to cause systemic inflammation that leads to autoimmunity.

3. Toxins

Toxic molds (mycotoxins) and heavy metals such as mercury are the two main toxins I see in those with autoimmune conditions. Mycotoxins are very volatile compounds produced by toxic molds that wreak havoc on the immune system.

We are exposed to heavy metals like mercury in different ways: mercury amalgam fillings in teeth, fish consumption, and the environment. Mercury is toxic to our bodies and can be one piece of the puzzle for those with autoimmune diseases.

4. Infections

Scientists have long suspected that infections from bacteria, viruses, and other toxins were likely to blame for the development of autoimmunity. And while they have not been able to identify one single culprit, they have found strong correlations between a number of bacteria and viruses.

5. Stress

Stress disrupts immune function through several distinct pathways. Stress is the body’s response to a threat — a wound, injury, or infection. Chronic stress (the kind we face in this day and age) leads to longterm inflammation that never really shuts off, creating autoimmune disease. Once the autoimmune response is in place, immediate stress only exacerbates it.

My Approach To Reversing Autoimmune Disease

1. Remove gluten, grain and legumes from diet.

For my patients with autoimmune diseases, I highly recommend removing not only gluten but all grains and legumes from their diet. These foods contain proteins known as lectins, which act as a natural pesticide for crops and can wreak havoc on the lining of your gut. Changing your diet is the first step in getting well.

2. Heal the gut.

Healing the gut is essential to healing yourself. After all, 80% of your immune system lies in your gut! Avoid foods and, if possible, medications that damage the intestinal lining and restore the balance of your body’s bacterial flora, and your inflammation will subside. Sometimes it can be tricky to identify the foods that are a problem for you. I recommend trying an elimination diet (avoiding certain foods for a period of time and then reintroducing them, one at a time, while gauging your symptoms) to find your personal food sensitivities.

3. Test for heavy metals and mycotoxins.

If your diet is high in tuna, Atlantic salmon, swordfish or other mercury-containing fish, consider reducing your intake or avoiding them altogether. Choose fish that have lower mercury content, like Pacific-caught salmon, tilapia, trout, and flounder. In addition I recommend a DMPS challenge test and that all my patients find a biological dentist to remove their mercury amalgam fillings.

4. Find and treat infections.

There are a number of bacterial and viral infections that have been associated with autoimmune conditions. Have your doctor test for these infections.

5. Manage stress.

I tell all my patients that they should prioritize stress reduction. Take care of yourself by adopting some stress-relieving strategies, such as exercise, meditation and art. If you are having trouble relaxing, try a yoga class or a guided meditation. Even giving yourself five minutes to sit quietly with a fragrant cup of herbal tea can help tremendously.

My approach is based on getting to the root of the problem: removing the elements that derailed your immune system in the first place and strengthening your immune system rather than suppressing it. That’s why using this approach enables you to reverse and prevent many different autoimmune conditions at once.