- When the immune system goes on the attack
- Newly Discovered Immune Cell Linked to Type 1 Diabetes
- How Lupus Affects the Immune System
- T-cells, B-cells, and Antibodies
- What Are Common Symptoms of Autoimmune Disease?
- Common Autoimmune Disease Symptoms
- Autoimmune Disease: Why Is My Immune System Attacking Itself?
- The Link Between Autoimmune Disease and Women
- The Role of Infection and Disease
- The Damage Theory
- Genetic Risk
- Autoimmune Disease in Functional Medicine Genetic Optimization
- Environmental Toxins and Autoimmune Disease
- Functional Medicine – Treating the Causes of Your Autoimmune Disease
- Do you suffer from an autoimmune disease? Here are my recommendations:
When the immune system goes on the attack
Eileen O'Connor of New York City had been suffering for more than three years and neither she—a nurse, healthcare lawyer and epidemiologist—nor numerous specialists could make sense of her symptoms: persistent respiratory infections, a collapsed lung, difficulty breathing, repeated falls, broken bones and torn cartilage.
Only recently did she learn that she has systemic lupus erythematosus (SLE), an elusive autoimmune disease (AD) that affects the lungs, muscles, brain, heart and kidneys.
Explaining why it was so difficult to diagnose, Joan Merrill—Professor of Medicine at the University of Oklahoma's Health Sciences Center (Oklahoma City, OK, USA)—said, “lupus shows extreme variability in what organ or organs it attacks.”
lupus, many ADs are difficult to diagnose and treat.
Some affect multiple organ systems, whereas others, such as rheumatoid arthritis (RA), antibody-mediated thrombosis, Sjögren's syndrome, myasthenia gravis, type 1 diabetes and Graves' disease, target primarily one organ, although they can also wreak havoc in other organs, including the pancreas (arthritis) and the heart (hyperthyroidism, diabetes and RA).
And truly effective treatment is available for only a few diseases, such as Graves' disease. “For most of these diseases, the concept of remission does not even exist,” commented Richard Burt, Associate Professor of Medicine at the Feinberg School of Medicine, Northwestern University (Chicago, IL, USA).
The common characteristic of all ADs is an immune system that attacks healthy tissues, thus provoking inflammation, as well as tissue and organ damage. Autoimmunity is present to some extent in everyone, but it usually causes no harm.
ADs, however, progress to a pathogenic state that involves the whole immune system: antigens, antigen-presenting cells, T and B lymphocytes, messenger molecules, cytokines, chemokines and their receptors, and signalling and co-stimulatory molecules (Mackay, 2000).
There are an estimated 80 ADs, which affect 14–22 million Americans, or 5%–8% of the population, and their prevalence is on the rise, according to the US National Institutes of Health (NIH).
ADs affect a disproportionate number of women—the female to male ratio is 50:1 in Hashimoto's syndrome (hypothyroiditis), 9:1 in lupus, primary biliary cirrhosis and antiphospholipid syndrome, 7:1 in Graves' disease, 4:1 in RA and 2:1 in multiple sclerosis (MS) and myasthenia gravis.
Others strike particular ethnic groups more frequently: lupus is three times as common in African Americans and Latinos/Hispanics, whereas MS and type 1 diabetes are seen more frequently in Caucasians. “The predominance of AD among women suggests that sex hormones may modulate susceptibility,” according to Caroline Whitacre, Professor and Chair of Molecular Virology, Immunology and Medical Genetics at Ohio State University (Columbus, OH, USA).
The central role of sex hormones is quite obvious, as they modulate T-cell receptor signalling, activation of cytokine genes and lymphocyte homing.
Ongoing research by Betty Diamond at the Albert Einstein College of Medicine (Bronx, NY, USA) indicates that oestrogen may in fact predispose women to SLE by reducing B-cell tolerance and dampening apoptotic processes (Bynoe et al, 2000).
A new study (Kramer et al, 2004) from the Baylor College of Dentistry (Dallas, TX, USA) showed that decreasing oestrogen levels set off a chain reaction of inflammation. Research on knockout mice also demonstrated that the oestrogen receptor mediates a variety of ADs (Liu et al, 2003).
In addition, genetic studies have revealed that different ADs may share the same susceptibility genes, such as lupus and RA (Helms et al, 2003; Tokuhiro et al, 2003). In fact, ADs run in families: a mother may have rheumatoid arthritis, her sister psoriasis and a daughter lupus. And patients afflicted with one organspecific AD are often subsequently diagnosed with another.
“For most of these diseases, the concept of remission does not even exist”
Infectious diseases also seem to have a significant role in the pathogenesis of ADs. Immune cells responding to infection can cross-react with normal tissues, leading to an autoimmune response, explained Michael Oldstone, head of the Viral Immunobiology Laboratory at the Scripps Research Institute (La Jolla, CA, USA).
“In molecular mimicry, a small number of selfreactive T-cells are expanded with cross-reactive epitopes to produce a quantity of T-cells sufficient to create disease,” he said. “The initial insult is often an infection, which affects a target tissue, such as the brain or pancreas, but does not cause disease.
The infection may be cleared, but when the insult is repeated, self-reactive cells are expanded from a few autoreactive cells.” Oldstone's work links lymphocytic choriomeningitis virus with type 1 diabetes.
Other researchers are investigating the role of human herpes virus 6 and Epstein–Barr virus in MS, Helicobacter pylori in gastric autoimmunity (Amedei et al, 2003) and Listeria and Mycobacterium avium in Crohn's disease.
Noel Rose, Professor at Johns Hopkins University's Bloomberg School of Public Health (Baltimore, MD, USA) and Director of its Center for Autoimmune Disease Research, is studying how group B coxsackieviruses induce autoimmune myocarditis in genetically predisposed mice. He identified key cytokines produced during viral infection that determine the development of autoimmunity and showed that blocking these prevents autoimmune myocarditis.
Treating ADs remains a delicate balancing act. “Two approaches are possible with ADs: slightly dampening down the entire immune system, and targeting one part of it,” said Merrill. “Probably, the optimal approach would be combining both types of treatments.
” Until the last decade, the major weapons against an overactive immune system were steroids, chemotherapy and major immunosuppressants—very blunt instruments with serious side effects.
Better treatments come from the discovery of new targets and the development of monoclonal antibodies, antisense RNA and other drugs that target only parts of the immune system by blocking specific molecules in the inflammatory pathway.
The first generation of these therapeutics, primarily directed against cytokines, are monoclonal antibodies.
Amgen's (Thousand Oaks, CA, USA) ENBREL® (etanercept), Centocor's (Malvern, PA, USA) Remicade® (infliximab) and Abbott Laboratories' (Abbott Park, IL, USA) HUMIRA® (adalimumab), which interfere with the pro-inflammatory tumour necrosis factor-α, have already become bestsellers for treating RA. Amgen's Kineret® (anakinra) is an antagonist to the interleukin-1 receptor, another proinflammatory cytokine. These drugs avoid some of the more serious side effects that are associated with steroids, but most still increase the risk of infections.
Treating ADs remains a delicate balancing act
Other specific drug targets include adhesion molecules, which promote T-cell migration, aggregation and activation, ICE (interleukin-β-converting enzyme) and cytotoxic-T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig), a T-cell regulatory protein that acts as an 'off' switch for the whole immune system. Protein Design Labs' (Fremont, CA, USA) Nuvion® (visilizumab) targets the CD3 receptor on T cells to treat psoriasis. The Immune Response Corp. (Carlsbad, CA, USA) is developing a vaccine for MS, NeuroVax™, which downregulates pathogenically activated T cells. Antisense drugs in development include a candidate for treating psoriasis by inhibiting insulin- growth factor 1 receptor (IGF1r; Antisense Therapeutics Ltd, Toorak, Victoria, Australia), and Isis' (Carlsbad, CA, USA) inhibitor of CD49d, which prevents white blood cells from leaving the blood and entering the central nervous system, to stop the progression of MS.
…work to identify, prevent, treat or even reverse an autoimmune disease is most advanced for type 1 diabetes, because the main culprits … have been known for a long time
As many ADs share underlying immune system defects, various drugs are also being tested for different diseases: Remicade, used by half a million people for RA in the USA, is now in trials for Crohn's disease, and Enbrel was recently approved in the USA for treating psoriasis. Biogen Idec's (Cambridge, MA, USA) and Elan's (Dublin, Ireland) Antegren® (natalizumab), a selective adhesion molecule inhibitor designed to inhibit certain immune cells from migrating into chronically inflamed tissue, is being tested for MS, Crohn's disease and RA, and Nuvion is being tested for severe ulcerative colitis. This June, a British-Polish study showed that Rituxan® (rituximab), an antibody developed by Genentech (San Francisco, CA, USA) to treat lymphoma, is also effective against RA (Edwards et al, 2004).
Equally important is improving diagnosis, because early identification of susceptible patients may help to treat them and prevent disease progression before the onset of symptoms. A recent study (Scofield, 2004) showed that it might indeed be possible to predict ADs years before illness appears by measuring auto-antibodies.
Hal Scofield, Professor of Medicine at the University of Oklahoma's Health Sciences Center, reviewed the blood samples of six million US military personnel, taken routinely on induction and then every two years after that.
He traced the existence and persistence of various auto-antibodies over a decade, and correlated them to individuals who ultimately received lupus diagnoses. “Antinuclear antibodies and anti-Ro appeared as early as 10 years before first onset of [SLE] disease,” Scofield said.
“Except in diabetes, it had not been shown before that the respective auto-antibodies preceded the emergence of disease.
” He also cited other studies showing that the existence of other antibodies can predict who will develop RA, primary biliary cirrhosis, autoimmune thyroid disease and type 1 diabetes, a median of 4–5 years before disease onset. “If you can identify a patient before he becomes ill, it may be possible to use an immunomodulatory strategy to prevent him from becoming ill,” Scofield said.
Such work to identify, prevent, treat or even reverse an autoimmune disease is most advanced for type 1 diabetes, because the main culprits—the antibodies targeting the insulin—producing β-cells-have been known for a long time. Several current studies examine auto-antibodies that appear in at-risk individuals before diabetes develops.
Two NIH-sponsored trials will investigate the immune and metabolic events leading to disease onset in individuals with certain antibodies, and try to stop or delay the destruction of β-cells using drugs that have been approved to prevent organ rejection (www.diabetestrialnet.org). Others aim at specific antibodies.
In 1993, Daniel Kaufman of the University of California Los Angeles's School of Medicine cloned the glutamic acid decarboxylase (GAD) gene and showed that a GAD vaccine could inhibit diabetes in mice with established autoimmune responses. On the basis of his work, Diamyd Medical (Stockholm, Sweden) is testing a drug against GAD antibodies.
At the end of March, Diamyd reported data from a phase II trial showing that its drug increased insulin production in patients with a slowly progressing diabetes, called latent autoimmune diabetes. The next trial will treat new-onset type 1 diabetes, with the goal of arresting the destruction of remaining β-cells.
Diabetogen (London, Ontario, Canada) is also developing a human T-cell-targeting monoclonal antibody with Abgenix (Fremont, CA, USA) to reverse disease onset.
But perhaps the best hope for long-term remissions in ADs is … to 'reset' the whole immune system by replacing it with fresh cells
Other advances aim to replace lost β-cells, including islet transplantation, implanting encapsulated porcine pancreatic β-cells (MicroIslet Inc., San Diego, CA, USA), transforming human fetal liver cells into insulin-producing cells, isolating pancreatic progenitor cells and transforming adult murine bone marrow cells to produce insulin.
Last autumn, researchers at the Joslin Diabetes Center (Boston, MA, USA) even reversed autoimmune diabetes in mice by injecting spleen cells from a different mouse type together with an immunostimulatory drug (Kodama et al, 2003).
But islet transplantation has had limited success due to a dearth of available organs and because immunosuppression that is used to induce tolerance to foreign cells actually kills those cells, according to Gordon Weir, Head of Islet Transplantation and Cell Biology at Joslin and Professor of Medicine at Harvard Medical School (Cambridge, MA, USA).
Nevertheless, improvements are yielding results and about half of the recipients need no more insulin injections after their islet transplants (Robertson, 2004).
But perhaps the best hope for long-term remissions in ADs is coming from autologous haematopoietic stem-cell transplants (HSCTs) that 'reset' the whole immune system by replacing it with fresh cells.
Richard Burt got this idea 14 years ago when working with cancer patients. “I noticed that patients who had had bone marrow transplants had to be re-immunised for infectious diseases because they'd lost their immune memory,” he said.
So began a plan to regenerate a naive immune system from uncommitted, newly developing stem cells.
“The concept of autologous HSCT presumes that the autoimmune disease is environmentally induced and not a genetic stem cell defect,” Burt said. As his goal is immune suppression rather than destruction of bone marrow, he uses drugs, not radiation, which has decreased the risk of mortality fourfold.
Infusing stem cells after immune suppression also results in faster patient recovery. Burt began testing HSCT eight years ago, and first reported positive results in lupus, MS and RA in the late 1990s.
In 2003, he started using HSCT on Crohn's disease, and other researchers have tested it in scleroderma and juvenile chronic arthritis. Altogether, about 600 HSCTs have been performed in Europe and Asia, and 209 in the USA.
Overall, Burt sees more benefit in patients who are less severely affected by their disease. Furthermore, when patients do relapse after HSCT—as do about one-third of those with lupus—drugs usually restore remissions.
Newly Discovered Immune Cell Linked to Type 1 Diabetes
‘Rogue defender’ mistakenly spurs attacks on insulin-producing cells in pancreas
Colorized scanning electron micrographs of a B and T lymphocyte shown with a fluorescent microscopy image of the previously unseen “X lymphocyte,” which is a hybrid of the other two immune cells. Credits: B and T cell images from the National Institute of Allergy and Infectious Diseases; X cell image from Department of Pathology, Johns Hopkins University School of Medicine
In a discovery that might be ned to finding medicine’s version of the Loch Ness monster, a research team from Johns Hopkins Medicine, IBM Research and four collaborating institutions is the first to document the existence of long-doubted “X cell,” a “rogue hybrid” immune system cell that may play a key role in the development of type 1 diabetes.
The researchers report the unusual lymphocyte (a type of white blood cell) — formally known as a dual expressor, or DE, cell — in a new paper published in the journal Cell.
“The cell we have identified is a hybrid between the two primary workhorses of the adaptive immune system, B lymphocytes and T lymphocytes,” says Abdel-Rahim A. Hamad, M.V.Sc., Ph.D.
, associate professor of pathology at the Johns Hopkins University School of Medicine and one of the authors of the paper.
“Our findings not only show that the X cell exists, but that there is strong evidence for it being a major driver of the autoimmune response believed to cause type 1 diabetes.”
Type 1 diabetes, formerly known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which there is destruction of the beta cells in the pancreas that produce insulin, the hormone that regulates a person’s blood sugar level.
Diagnosed mostly in childhood but present at all ages, the disease accounts for between 5% and 10 % of all diabetes cases in the United States or about 1.3 million people.
Although most experts believe it to be an autoimmune disorder — where the immune system mistakes normal, healthy beta cells as hazards and eliminates them — the underlying mechanism at the cellular level has been difficult to define.
Hamad and his colleagues believe that they may be the first to do so. However, they caution that more analysis is required to directly link the X cell to the development of type 1 diabetes.
“What is unique about the entity we found is that it can act as both a B cell and a T cell,” Hamad says. “This probably accentuates the autoimmune response because one lymphocyte is simultaneously performing the functions that normally require the concerted actions of two.”
B and T lymphocytes each possess distinctly different cell receptors — the B cell receptor, or BCR, and T cell receptor, or TCR, respectively — that work together to help identify and target antigens; the bacteria, viruses and other foreign invaders that trigger an immune response. Normally, this defense begins when the trespasser is engulfed by a white blood cell called an antigen presenting cell, or APC. The name arises from the fact that an antigenic protein from the ingested intruder is “presented” on the surface of the APC.
After this occurs, the APC travels to a part of the body, such as a lymph node, where immature B and T cells reside. A T cell with a TCR whose shape conforms to the presented antigen — akin to fitting a key into a lock — can latch on, triggering its maturation into either a helper or killer T cell.
Helper T cells then activate immature B cells whose BCRs also conform to the shape of the presented antigen to mature them into either plasma cells that produce antibodies to remove the foreign material from the body or memory cells that “remember’ the antigen’s biochemistry for a faster response to future invasions.
Killer, or cytotoxic, T cells, on the other hand, directly attack the invaders to which they’ve been primed as a result of the immature T cell’s initial contact with the antigen.
However, when this process goes haywire with the B cells and T cells seeking out and attacking normal cells — the case of mistaken identity known as an autoimmune response — the results can be devastating.
For type 1 diabetes, scientists have long believed that the immune system somehow becomes confused and sees insulin as a target. Therefore, the misguided cellular defense forces wage war on the beta cells in the pancreas that produce the hormone, drastically lowering the amount available and leading to the high blood sugar levels characteristic of diabetes.
What isn’t well understood is the mechanism that drives the assault against the beta cells. The DE cell identified by Hamad and his colleagues — and a unique protein that it produces — appear to be the key agents for at least one possible pathway.
“It is well accepted that insulin is seen as an antigen by the T cells and that this occurs when the hormone is bound to a site on the APC known as HLA-DQ8,” Hamad explains. “However, our experiments indicate that it is a weak binding and not ly to trigger the strong immune reaction that leads to type 1 diabetes.”
Instead, the findings from the new study show that when a second protein — one coded by the BCR present on the DE cell — is substituted for insulin, it binds so tightly that it can elicit a T cell response 10,000 times stronger.
Computer simulations conducted by Ruhong Zhou, Ph.D., and his team at the IBM Thomas J. Watson Research Center were used to reveal the underlying molecular mechanism for the unusual binding of the DE cell protein, known as the x-Id peptide, and predict the strength of the T cell response to it.
Additional simulations confirmed the x-Id peptide’s power, showing that it also displayed a tenfold increase in T cell activity over a laboratory-engineered “superagonist” insulin mimic that was genetically altered to create a more antigenic molecule (and is itself 1,000 times more immune stimulating than normal insulin).
|Computer simulation showing the extremely tight binding to an immune system cell of a peptide (blue) produced by the newly discovered “X lymphocyte.” The protein may direct the mistaken destruction of healthy insulin-producing cells in the pancreas, and in turn, cause type 1 diabetes. This autoimmune response is 10 times stronger than that seen with a weaker-binding, lab-engineered insulin mimic (red) that is itself 1,000 times more immune stimulating than normal insulin.Credit: IBM Thomas J. Watson Research Center|
Different methods were used to verify the existence of the DE cell and define its characteristics, including modifying DE cells using a virus to give rise to a large number of DE cell clones (genetically exact duplicates). The researchers found that every clone possessed both BCRs and TCRs, proving that the lymphocyte was truly a hybrid of B and T cells.
Perhaps the most intriguing part of the “X cell story” is that the researchers found DE lymphocytes and the x-Id peptide more frequently in the blood of type 1 diabetes patients than in healthy, nondiabetic subjects. “This finding, combined with our conclusion that the x-Id peptide primes T cells to direct the attack on insulin-producing cells, strongly supports a connection between DE cells and type 1 diabetes.”
Next, Hamad says, his team will study that probable link in greater depth to confirm and more extensively define it. He says that such knowledge could lead to the development of methods to screen individuals at risk for developing type 1 diabetes.
“It also is possible that this study could lay the groundwork for developing immunotherapies that target DE cells for elimination or genetically alter the lymphocytes so that they cannot stimulate an immune response,” says Thomas Donner, M.D., director of the Johns Hopkins Diabetes Center and a co-author of the study.
Quite remarkable, Hamad says, for a “biological Nessie” that most experts told him didn’t exist.
“We were willing to take the risk and look at something different, and now we may have taken the first steps toward finding new strategies to cure type 1 diabetes,” he says. “We also may one day find that DE cells are involved in the pathology of other autoimmune disorders such as multiple sclerosis and rheumatoid arthritis.”
Besides the contributors from the Johns Hopkins University School of Medicine, the Johns Hopkins Bloomberg School of Public Health and IBM, the research team includes members from the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine, Columbia University, Des Moines University and Massachusetts General Hospital.
This work was supported by grants from the National Institutes of Health (R0 AI099027) and the Norman Raab Foundation.
How Lupus Affects the Immune System
The immune system is an elaborate network of cells, tissues, and organs that helps to protect the body from invaders (bacteria, viruses, fungal infections, and parasites).
Usually, the immune system develops only to act upon foreign substances, and immune system cells that try to combat cells of the body are weeded out during the development process.
However, in lupus and other autoimmune diseases, the immune system begins to recognize and attack “self.” In other words, the cells of the immune system begin to injure the body’s own tissues.
This phenomenon is similar to “friendly fire” and can cause permanent scarring that ultimately jeopardizes the function of certain organs and systems in the body. Certain cells and processes of the immune system have been identified as playing a role in lupus.
T-cells, B-cells, and Antibodies
A group of white blood cells called lymphocytes plays a key role in the human immune response. Lymphocytes include cells called B-cells and T-cells that are responsible for flagging and fighting infections in healthy individuals.
Antigens are substances that elicit the response of T-cells and B-cells in the body. When a T-cell recognizes a specific antigen, it binds to the substance and produces chemicals called cytokines.
Cytokines then cause B-cells to multiply, and some of these B cells turn into plasma cells that secrete antibodies (immunoglobulins). [The response of B cells is referred to as the “humoral” response; T-cell activation is called the “cell-mediated” immune response.
] These antibodies then circulate in the bloodstream so that when they encounter the antigen again, they bind to it, forming a complex that is then acted on by other cells of the immune system in an effort to destroy the invader.
Usually, remnants of these complexes are removed from the body by a garbage disposal system that involves the spleen.
T-cells are classified as killer-T cells, helper-T cells, or suppressor T-cells. Killer-T cells have the ability to recognize and destroy infected cells in the body.
Helper-T cells, however, can only identify viruses engulfed by special cells called macrophages.
The macrophage presents the antigen to the helper-T cell, which responds by producing the cytokines that stimulate B cells to multiply and release antibodies.
In healthy individuals, the masses of cells that gather at an infected or injured site in the body produce factors that help fight off the infection.
This process causes some inflammation and injury of healthy tissue, but usually the immune system possesses other factors that help to control this inflammatory process. In individuals with lupus, both B cells and T cells become overactive.
The two main consequences of this increased activity are the production of autoantibodies (antibodies that recognize and destroy the body’s own cells) and inflammation that can lead to long-term, irreversible scarring.
The production of autoantibodies in people with lupus and other autoimmune diseases causes the immune system to target the body’s own cells for destruction.
For example, about 98% of people with lupus possess antinuclear antibodies (ANA), which can attack the nucleic material of your cells.
In addition, some individuals may possess anti-phospholipid antibodies, which damage proteins bound to phospholipids in the membranes of your cells. These autoantibodies are linked to pregnancy complications, stroke, heart attacks, and other blood clots.
In addition, regulatory T cells, which are supposed to control the system, are deficient in SLE.
Neutrophils are the most common type of white blood cell in your body; whereas lymphocytes are involved in the ongoing immune response, neutrophils are the first line of attack against invaders.
Inflammation in a healthy individual usually signals that the body’s immune system is responding appropriately to pathogens, damaged cells, irritants, or injury.
However, in lupus, neutrophils cause increased inflammation due to certain interactions between an individual’s blood plasma and other immune system cells (specifically, complement, cytokines, and cell adhesion molecules).
Even though increased inflammation may cause pain and discomfort, the major problem with inflammation is potential long-term irreversible scarring. It is important that you and your doctor discuss medications to curb the inflammatory processes involved in lupus in order to minimize long-term damage to important organs.
Cytokines are signaling molecules involved in regulation of an individual’s immune response. Some cytokines amplify the immune response, while others tone it down. Some people with lupus and similar autoimmune diseases have a greater ratio of proinflammatory to anti-inflammatory cytokines than normal individuals, which produces an unbalanced regulatory mechanism.
While an overall cause-and-effect relationship between cytokines and lupus is not yet understood, certain cytokines called interferons and interleukins are associated with the disease. In general, however, the overproduction of such molecules causes the immune system to become overactive, leading to increased inflammation and tissue injury.
Complement proteins interact in a sequential manner to clear immune complexes from your body. Deficiencies of certain complement proteins are associated with lupus. In addition, since complement proteins are consumed during inflammatory processes, low complement levels may indicate lupus activity.
- Dean, Gillian S., et al. “Cytokines and systemic lupus erythematosus.” Ann Rheum Dis 2000; 59: 243–251.
- “Systemic lupus erythematosus.” In-Depth Patient Education Reports. Ed. Harvey Simon. 21 Jan. 2008. University of Maryland Medical Center. 25 June 2009 .
- Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995.
What Are Common Symptoms of Autoimmune Disease?
Between taking care of yourself and family members and trying to manage a social life and career, it’s common for women to feel tired and achy. But are these symptoms of a stressful life, or could they be tied to an underlying condition autoimmune disease?
Ana-Maria Orbai, M.D., M.H.S., is a rheumatologist at the Johns Hopkins Arthritis Center. Rheumatologists specialize in diagnosing and treating musculoskeletal diseases and autoimmune conditions (rheumatic disease). Orbai talks about how to recognize common autoimmune disease symptoms and when you should see a doctor.
Autoimmune disease happens when the body’s natural defense system can’t tell the difference between your own cells and foreign cells, causing the body to mistakenly attack normal cells. There are more than 80 types of autoimmune diseases that affect a wide range of body parts.
The most common autoimmune diseases in women are:
- Rheumatoid arthritis, a form of arthritis that attacks the joints
- Psoriasis, a condition marked by thick, scaly patches of skin
- Psoriatic arthritis, a type of arthritis affecting some people with psoriasis
- Lupus, a disease that damages areas of the body that include joints, skin and organs
- Thyroid diseases, including Graves’ disease, where the body makes too much thyroid hormone (hyperthyroidism), and Hashimoto’s thyroiditis, where it doesn’t make enough (hypothyroidism) of the hormone
Symptoms of autoimmune disease may be severe in some people and mild in others. “There are different degrees of autoimmune disease,” says Orbai. “The symptoms a person gets ly relate to multiple factors that include genetics, environment and personal health.”
Common Autoimmune Disease Symptoms
Despite the varying types of autoimmune disease, many of them share similar symptoms. Common symptoms of autoimmune disease include:
- Joint pain and swelling
- Skin problems
- Abdominal pain or digestive issues
- Recurring fever
- Swollen glands
Many women say it’s hard to get diagnosed, something that Orbai agrees with. “It’s not black or white,” she says. “There’s usually no single test to diagnose autoimmune disease. You have to have certain symptoms combined with specific blood markers and in some cases, even a tissue biopsy. It’s not just one factor.”
Diagnosis can also be difficult because these symptoms can come from other common conditions. Orbai says women should seek treatment when they notice new symptoms.
“If you’ve been healthy and suddenly you feel fatigue or joint stiffness, don’t downplay that,” she says. “Telling your doctor helps him or her to look closer at your symptoms and run tests to either identify or rule out autoimmune disease.”
Autoimmune disease affects 23.5 million Americans, and nearly 80 percent of those are women. If you're one of the millions of women affected by this group of diseases, which includes lupus, rheumatoid arthritis and thyroid disease, you may be wondering why your immune system is attacking itself.
Researchers don’t know what causes autoimmune disease, but several theories point to an overactive immune system attacking the body after an infection or injury. We do know that certain risk factors increase the chances of developing autoimmune disorders, including:
- Genetics: Certain disorders such as lupus and multiple sclerosis (MS) tend to run in families. “Having a relative with autoimmune disease increases your risk, but it doesn’t mean you will develop a disease for certain,” says Orbai.
- Weight: Being overweight or obese raises your risk of developing rheumatoid arthritis or psoriatic arthritis. This could be because more weight puts greater stress on the joints or because fat tissue makes substances that encourage inflammation.
- Smoking: Research has linked smoking to a number of autoimmune diseases, including lupus, rheumatoid arthritis, hyperthyroidism and MS.
- Certain medications: “Certain blood pressure medications or antibiotics can trigger drug-induced lupus, which is often a more benign form of lupus,” Orbai says. “Our myositis center also discovered that specific medications used to lower cholesterol, called statins, can trigger statin-induced myopathy.” Myopathy is a rare autoimmune disease that causes muscle weakness. Before starting or stopping any medications, however, make sure to talk to your doctor.
Having lupus, rheumatoid arthritis or psoriatic arthritis raises your risk for heart disease. While taking steps to reduce heart disease is always a good idea, it is even more essential if you have one of these conditions.
Talk to your doctor about what you can do to keep your heart healthy and strong.
For example, keeping your blood pressure and cholesterol levels within healthy ranges, eating a nutritious diet and exercising regularly can be lifesaving.
These steps can also help reduce the symptoms of autoimmune disease. Orbai admits that making time for healthy living can be hard, given women’s fast-paced lives, but she insists that finding the balance is key to living with autoimmune disease.
“It’s something that’s going to involve commitment, and sometimes it’s going to be tough,” she says. “But learning to listen to your body and being smart about what triggers your disease is important. It’s something you do for yourself.”
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Autoimmune Disease: Why Is My Immune System Attacking Itself?
Autoimmune disease affects 23.5 million Americans, and nearly 80 percent of those are women. If you’re one of the millions of women affected by this group of diseases, which includes lupus, rheumatoid arthritis and thyroid disease, you may be wondering why your immune system is attacking itself.
Ana-Maria Orbai, M.D., M.H.S., is a rheumatologist at the Johns Hopkins Arthritis Center. Rheumatologists specialize in diagnosing and treating musculoskeletal diseases and autoimmune conditions (rheumatic disease). Orbai explains several theories researchers have about what might cause autoimmune disease, including infection, tissue damage and genetics.
The Link Between Autoimmune Disease and Women
Doctors aren’t sure why autoimmune disease happens in the first place or why women are affected more than men. One theory is that higher levels of hormones in women, especially during the childbearing years, could make women more susceptible to autoimmune diseases.
However, Orbai notes that this idea has not yet been proven — there are many factors that affect autoimmunity, both genetic and environmental. Researchers cannot definitively explain why women develop these diseases more than men do.
The Role of Infection and Disease
On a basic level, autoimmune disease occurs because the body’s natural defenses — the immune system — attack the body’s own healthy tissue. Researchers have several ideas about why this happens.
When the body senses danger from a virus or infection, the immune system kicks into gear and attacks it. This is called an immune response. Sometimes, healthy cells and tissues are caught up in this response, resulting in autoimmune disease.
Many scientists believe this is what causes rheumatoid arthritis, a type of autoimmune disease that attacks the joints. It’s also common that after having strep throat, people develop psoriasis, an autoimmune condition that causes patches of thick, scaly skin.
Other types of autoimmune disease may come from the body trying to fight specifically against cancer cells. Orbai points to scleroderma, a disease that causes thickening of the skin and connective tissues.
“The thought is that when the immune system gets rid of the cancer, there is a leftover inflammatory response because of that fight,” she says.
Johns Hopkins researchers studied patients who developed both scleroderma and cancer to try to clarify this relationship.
The Damage Theory
Scientists think injury may play a role in some types of autoimmune disease such as psoriatic arthritis, a condition that affects the joints of some people with psoriasis.
Research has shown that in parts of the body subjected to high stress, an autoimmune response happens after damage to tendons, which attach muscle to bone. For example, a runner’s heel is an area where the muscle is constantly pulling on the bone to create movement.
“This repeated stress can expose tissue that shouldn’t normally be in contact with blood cells,” says Orbai. “When that tissue gets exposed, it’s a small wound. Blood cells try to heal it, but an abnormal immune response causes inflammation of the joints and tendons.”
Orbai is quick to point out that while there is some data to support them, scientists have not proven that these are causes of autoimmune disease.
It’s clear that genetics play a role in autoimmune disease, but researchers still don’t fully understand how. For example, having a family member with lupus or multiple sclerosis (MS) raises your risk of getting these diseases. Some families have multiple members affected by different autoimmune diseases. However, genetics alone isn’t enough to cause autoimmune disease.
“We know that genes are important, but they aren’t everything,” Orbai says. “You can have family members with lupus or MS and never get them yourself. You can even test positive for lupus-specific DNA and still not have the disease.”
It’s possible that autoimmune disease occurs the immune system’s ability to handle stress. Orbai says that this is an area of intense research. “When does the stress on your body exceed your immune system’s ability to handle it? If we knew this, it could be the key to preventing autoimmune disease before it develops.”
Autoimmune Disease in Functional Medicine Genetic Optimization
You're probably familiar with the most common autoimmune diseases, rheumatoid arthritis, lupus, multiple sclerosis, inflammatory bowel disease, type-1 diabetes, hypothyroidism, and psoriasis.
But there are many more autoimmune diseases that affect the nervous system, joints and muscles, skin, endocrine gland, and heart. In fact, the incidence of autoimmune disease has tripled in the last few decades, affecting 24 million Americans.
More women are suffering from autoimmune diseases than heart disease and breast cancer combined. Autoimmune diseases are conditions where the body's immune system attacks its own tissues rather than a foreign invader a virus or bacteria. This happens when something confuses the immune system.
That “something” appears to be the enormous load of environmental toxins to which we are all exposed, and which creates a reaction against the self.
Environmental Toxins and Autoimmune Disease
Over 80,000 chemicals have been introduced into our society since 1900, and only 550 have been tested for safety. According to the US Environmental Protection Agency (EPA), about 2.5 billion pounds of toxic chemicals are released yearly by large industrial facilities.
Also, 6 million pounds of mercury are discharged into our air every year. The 2005 National Report on Human Exposure to Environmental Chemicals found an average of 148 chemicals in our bodies. And those were only the ones for which they tested.
More recently, the Environmental Working Group examined the umbilical cord blood of newborns and found 287 industrial chemicals, including pesticides, phthalates, dioxins, flame-retardants, Teflon, and toxic metals mercury.
These fetuses had been exposed to these toxins before they were born! (see Detoxification) Let’s not forget the pesticides found on our foods and those found in our homes as cleaning agents and pest control products, which add to our bodies’ total toxic load.
When it comes to toxins, I practice and recommend the precautionary principle, which says that we should avoid anything with the potential for harm. In the US, something has to be proven harmful before it is taken off the market. In Europe, something has to be proven safe before it is allowed on the market. This is also known as “better safe than sorry.”
Dr. Douglas Kerr, M.D., Ph.D., professor at Johns Hopkins School of Medicine, says in his foreword to The Autoimmune Epidemic, “there is no doubt that autoimmune diseases are on the rise and our increasing environmental exposure to toxins and chemicals is fueling the risk. The research is sound. The conclusions are unassailable.”
Although, it is clear that environmental toxins are a major cause of autoimmune disease, conventional medicine does not take that into account when treating autoimmune conditions.
Unfortunately, it attempts to shut down the patient’s immune response with powerful medications such as nonsteroidal anti-inflammatory drugs Advil or Aleve, steroids prednisone, anti-cancer drugs methotrexate, and new drugs Enbrel and Remicade that block the effects of a powerful inflammatory molecule called TNF alpha. These new drugs often provide only partial relief, while they induce frequent and serious side effects and shut down your immune system so forcefully that they increase your risk of cancer or life-threatening infections. These drugs may be lifesaving for some in the short run — but in the long run they do not address the cause of your illness.
Functional Medicine – Treating the Causes of Your Autoimmune Disease
If your roof is leaking, would you get an umbrella or do you fix the roof? Using the Functional Medicine approach, I have been treating many patients and watched them turning their health around by successfully addressing the underlying causes, such as toxins, infections, allergens, poor diet, and/or stress.
I have treated patients with severe arthritis, psoriasis, chronic fatigue, bloody diarrhea and pain of ulcerative colitis, multiple sclerosis, systemic lupus erythematosus, etc. For each one of them, I had to identify and resolve all the causes of their disease (i.e.
, toxins, allergens, infections, poor diet, and stress). Then together, we designed a healthy lifestyle program, which provided the things their body needed to function optimally, whole, clean food, nutrients, exercise, stress management, clean water and oxygen, emotional and spiritual support.
When patients follow the functional medicine approach, the results are amazing.
Do you suffer from an autoimmune disease? Here are my recommendations:
- Get tested for mercury and other heavy metals and unburden your body
- Get tested for celiac disease, an autoimmune reaction to wheat and other gluten-containing grains, which causes over 60 autoimmune diseases
- Identify your source of inflammation and treat it
- Test and eliminate all allergenic (inflammatory) foods from your diet
- Improve your immune function using a plant-based diet and supplements, including vitamin D, beneficial Omega-3 fats, and probiotics.
- Practice stress reduction techniques
- Improve your body's own detoxification system.
If your current approach has not resolved your symptoms and did not stop the progression of your autoimmune disease, it is time to address the root causes of your condition and start getting well today.