TEORI AUTOIMUNITAS

A.PendahuluanDalam keadaan normal, sistem imun dapat membedakan antigen tubuh sendiri dari antigen asing, karena tubuh mempunyai toleransi terhadap self antigen. tetapi pengalaman klinis menunjukkan bahwa adakalanya timbul reaksi autoimunitas.Reaksi autoimunitas adalah reaksi system imun terhadap antigen sel jaringan sendiri. Antigen tersebut disebut autoantigen, sedang antibody yang dibentuk disebut autoantibody. Sel autoreaktif adalah limfosit yang mempunyai reseptor untik autoantigen. Bila sel tersebut memberikan respons autoimun, disebut sel limfosit reaktif (SLR). Pada orang normal , meskipun SLR berpasangan dengan autoantigen, tidak selalu terjadi respon autoimun, karena ada system yang mengontrol reaksi autoimun.Kadang-kadang tidak jelas apakah autoantibody tersebut merupakan penyebab atau timbul sekunder akibat suatu penyakit. Oleh karena itu harus dibedakan antara fenomena autoimun dengan penyakit autoimun. Reaksi autoantibody dan autoantigen yang menimbulkan kerusakan jaringan dan gejala-gejala klinis disebut penyakit autoimun, sedangkan bila tidak disertai gejala klinis disebut fenomena autoimun.Burnett mengajukan teori forbidden clones, yang menyatakan bahwa tubuh menjadi toleran terhadap jaringannya sendiri oleh karena sel-sel yang autoreaktif selama perkembangan embriologiknya akan musnah.

B.Teori-teori autoimunitas1.Teori sequestered antigen atau hidden antigenSequestered aatau hidden antigen adalah antigen yang karena sawar anatomic tdk pernah berhubungan dengan system imun misalnya antigen sperma, lensa mata, dan saraf pusat. Bila sawar tersebut rusak, dapat timbul penyakit autoimmun

2.Teori defesiensi immunHilangnya self tolerance mungkin disebabkan oleh karena adanya gangguan system limfoid. Penyakit autoimmune sering ditemukan bersamaan dengan defesiensi imun, misalnya pada lanjut usia

3.Determinan antigen baruPembentukan autoantibody dapat dicetuskan oleh karena timbul deterrminan antigen baru pada protein normal. Contoh autoantibody yang timbul akibat hal tersebut ialah factor rematoid (FR). FR dibentuk terhadap determinan antigen yang terdapat pada immunoglobulin

4.Reaksi silang dengan mikroorganismeKerusakan jantung pada demam reumatik anak diduga terjadi akibat produksi antigen terhadap streptokok A yang bereaksi silang dengan miokard penderita

5.Virus sebagai pencetus autoimunitasVirus yang terutama mengginfeksi system limfoid dapat tmempengaruhi mekanisme kontrol imunologik sehingga terjadi autoimunitas

6.Autoantibodi dibentuk sekunder akibat kerusakan jaringanAutoantibodi terhadap jantung ditemukan pada jantung infark. Pada umumnya kadar autoantibody disini terlalu rendah untuk dapat menimbulkan penyakit autoimmun. Autoantibody dapat dibentuk pula terhadap antigen mitokondria pada kerusakan hati atau jantung. Pada tuberculosis dan tripanosomiasis yang menimbulkan kerusakan luas pada berbagai jaringan, dapat pula ditemukan autoantibody terhadap antigen jaringan dalam kadar gula yang rendah

C.Pembagian Penyakit AutoimmunPenyakit autoimmun dapat dibagi menajdi 2 golongan yaitu organ spesifik dan non spesifikOrgan spesifik

Non organ spesifikTiroiditis hasimotoMiksidema primerTirotoksotosisAnemia pernesiosaGastritis kronik autoimunPenyakit AddisonMenopause prematureDisbetes juvenileSindorm goodpastureMiastenia gravisInfertilitas pada priaPemfigus vulgarisPemfigoidOftalmia simpatisUveitis vagogenikSclerosis multipleAnemia hemolitik autoimunPurpura trombositopenik idiopatikLeucopenia idiopatikSirosis bilier primerHepatitis kronik aktif dengan HBsAg negativeSirosis kriptogenikColitis ulseratifSindrom SjögrenArthritis rematoid

DermatomiositisSclerodermaLE discoidLupus eritermatosus sistemik (SLE)

D.Kriteria Penyakit AutoimunKriteria untuk menegakkan diagnosis penyakit autoimmun adalah sebagai berikut :1.Penyakit timbul akibat adanya respons autoimun2.Ditemukan autoantibody3.Penyakit dpat ditimbulkan oleh bahan yang diduga merupakan antigen4.Penyakit dapat dipindahkan dari satu binatang ke binatang yang lain melalui serum atau limfosit yang hidup

What is the immune system? The immune system is the body's means of protection against microorganisms and other "foreign" substances. It is composed of two major parts. One component, B lymphocytes, produces antibodies, proteins that attack "foreign" substances and cause them to be removed from the body; this is sometimes called the humoral immune system. The other component consists of special white blood cells called T lymphocytes, which can attack "foreign" substances directly; this is sometimes called the cellular immune system. It takes time for both components of the immune system to develop. T lymphocytes become protective, and antibodies are developed after a person is exposed to specific "foreign" threats. Over a lifetime, the immune system develops an extensive library of identified substances and microorganisms that are cataloged as “threat” or “not threat.” Vaccinations utilize this process to add to the library. They expose a person’s immune system to weakened or inactivated forms of bacteria and viruses that can no longer cause disease, so that the person’s immune system will recognize them and create antibodies that will be ready to protect against the infectious forms of these microorganisms if the person comes in contact with them in the future.

Normally, the immune system can distinguish between “self” and “not self” and only attacks those tissues that it recognizes as “not self.” This is usually the desired response, but not always. When a person is given an organ transplant, the immune system will correctly recognize the new organ as “not self” (unless it is from an identical twin) and will attack it in a process called rejection. To prevent rejection, the transplant patient must take drugs that reduce the activity of the immune system (immunosuppressants) for the rest of his life.

What are autoimmune disorders? Autoimmune disorders are diseases caused by the body producing an inappropriate immune response against its own tissues. Sometimes the immune system will cease to recognize one or more of the body’s normal constituents as “self” and will create autoantibodies – antibodies that attack its own cells, tissues, and/or organs. This causes inflammation and damage and it leads to autoimmune disorders.

The cause of autoimmune diseases is unknown, but it appears that there is an inherited predisposition to develop autoimmune disease in many cases. In a few types of autoimmune disease (such as rheumatic fever), a bacteria or virus triggers an immune response, and the antibodies or T-cells attack normal cells because they have some part of their structure that resembles a part of the structure of the infecting microorganism.

Autoimmune disorders fall into two general types: those that damage many organs (systemic autoimmune diseases) and those where only a single organ or tissue is directly damaged by the autoimmune process (localized). However, the distinctions become blurred as the effect of localized autoimmune disorders frequently extends beyond the targeted tissues, indirectly affecting other body organs and systems. Some of the most common types of autoimmune disorders include:

 

Systemic Autoimmune Diseases Localized Autoimmune Diseases

Rheumatoid arthritis (RA) and Juvenile RA (JRA) (joints; less commonly lung, skin)

Type 1 Diabetes Mellitus (pancreas islets)

Lupus [Systemic Lupus Erythematosus] (skin, joints, kidneys, heart, brain, red blood cells, other)

Hashimoto's thyroiditis, Graves' disease (thyroid)

Scleroderma (skin, intestine, less commonly lung)

Celiac disease, Crohn's disease, Ulcerative colitis (GI tract)

Sjogren's syndrome (salivary glands, tear glands, joints)

Multiple sclerosis*

Goodpasture's syndrome (lungs, kidneys)

Addison's disease (adrenal)

Wegener's granulomatosis (blood vessels, sinuses, lungs, kidneys)

Primary biliary cirrhosis, Sclerosing cholangitis, Autoimmune hepatitis (liver)

Polymyalgia Rheumatica (large muscle groups)

Temporal Arteritis / Giant Cell Arteritis (arteries of the head and neck)

Guillain-Barre syndrome (nervous system)

 

 

* There is still some debate as to whether MS is an autoimmune disease

For a more complete list of autoimmune conditions, visit the Patient Information page of the American Autoimmune Related Diseases Association, Inc.

In some cases, a person may have more than one autoimmune disease; for example, persons with Addison's disease often have type 1 diabetes, while persons with sclerosing cholangitis often have ulcerative colitis.

In some cases, the antibodies may not be directed at a specific tissue or organ; for example, antiphospholipid antibodies can react with clotting proteins in the blood, leading to formation of blood clots within the blood vessels (thrombosis).

Autoimmune disorders are diagnosed, evaluated, and monitored through a combination of autoantibody blood tests, blood tests to measure inflammation and organ function, clinical presentation, and through non-laboratory examinations such as X-rays. There is currently no cure for autoimmune disorders, although in rare cases they may disappear on their own. Many people may experience flare-ups and temporary remissions in symptoms, others chronic symptoms or a progressive worsening. Treatment of autoimmune disorders is tailored to the individual and may change over time. The goal is to relieve symptoms, minimize organ and tissue damage, and preserve organ function. New treatments and a greater understanding of autoimmune disorders are being researched. Patients should talk to their doctors and to any specialists they are referred to about their treatment options.

What is lupus? What are the types of lupus?

Lupus is an autoimmune disease characterized by acute and chronic inflammation of various tissues of the body. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own immune system. The immune system is a complex system within the body that is designed to fight infectious agents, such as bacteria and other foreign microbes. One of the ways that the immune system fights infections is by producing antibodies that bind to the microbes. Patients with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than foreign infectious agents. Because the antibodies and accompanying cells of inflammation can affect tissues anywhere in the body, lupus has the potential to affect a variety of areas. Sometimes lupus can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the condition is called lupus dermatitis or cutaneous lupus erythematosus. A form of lupus dermatitis that can be isolated to the skin, without internal disease, is called discoid lupus. When internal organs are involved, the condition is referred to as systemic lupus erythematosus (SLE).

Both discoid and systemic lupus are more common in women than men (about eight times more common). The disease can affect all ages but most commonly begins from 20 to 45 years of age. Statistics demonstrate that lupus is somewhat more frequent in African Americans and people of Chinese and Japanese descent.

What causes lupus? Is it hereditary?

The precise reason for the abnormal autoimmunity that causes lupus is not known. Inherited genes, viruses, ultraviolet light, and certain medications may all play some role.

Genetic factors increase the tendency of developing autoimmune diseases, and autoimmune diseases such as lupus, rheumatoid arthritis, and autoimmune thyroid disorders are more common among relatives of patients with lupus than the general population. Some scientists believe that the immune system in lupus is more easily stimulated by external factors like viruses or ultraviolet light. Sometimes, symptoms of lupus can be precipitated or aggravated by only a brief period of sun exposure.

It also is known that some women with SLE can experience worsening of their symptoms prior to their menstrual periods. This phenomenon, together with the female predominance of SLE, suggest that female hormones play an important role in the expression of SLE. This hormonal relationship is an active area of ongoing study by scientists.

More recently, research has demonstrated evidence that a key enzyme's failure to dispose of dying cells may contribute the development of SLE. The enzyme, DNase1, normally eliminates what is called "garbage

DNA" and other cellular debris by chopping them into tiny fragments for easier disposal. Researchers turned off the DNase1 gene in mice. The mice appeared healthy at birth, but after six to eight months, the majority of mice without DNase1 showed signs of SLE. Thus, a genetic mutation in a gene that could disrupt the body's cellular waste disposal may be involved in the initiation of SLE.

In SLE, the body's immune system produces antibodies against itself, particularly against proteins in the cell nucleus. SLE is triggered by environmental factors that are unknown.

"All the key components of the immune system are involved in the underlying mechanisms" of SLE, according to Rahman, and SLE is the prototypical autoimmune disease. The immune system must have a balance (homeostasis) between being sensitive enough to protect against infection, and being too sensitive and attacking the body's own proteins (autoimmunity). From an evolutionary perspective, according to Crow, the population must have enough genetic diversity to protect itself against a wide range of possible infection; some genetic combinations result in autoimmunity. The likely environmental triggers include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus. Because of genetic variations in different components of the immune system, in some people the immune system attacks these nuclear-related proteins and produces antibodies against them. In the end, these antibody complexes damage blood vessels in critical areas of the body, such as the glomeruli of the kidney; these antibody attacks are the cause of SLE. Researchers are now identifying the individual genes, the proteins they produce, and their role in the immune system. Each protein is a link on the autoimmune chain, and researchers are trying to find drugs to break each of those links. [2][39][40]

SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement

What is drug-induced lupus?

Dozens of medications have been reported to trigger SLE. However, more than 90% of this "drug-induced lupus" occurs as a side effect of one of the following six drugs: hydralazine (used for high blood pressure), quinidine and procainamide (used for abnormal heart rhythms), phenytoin (used for epilepsy), isoniazid ([Nydrazid, Laniazid] used for tuberculosis), d-penicillamine (used for rheumatoid arthritis). These drugs are known to stimulate the immune system and cause SLE. Fortunately, drug-induced SLE is infrequent (accounting for less than 5% of all patients with SLE) and usually resolves when the medications are discontinued.

What are the symptoms and signs of lupus?

Patients with SLE can develop different combinations of symptoms and organ involvement. Common complaints and symptoms include fatigue, low-grade fever, loss of appetite, muscle aches, arthritis, ulcers of the mouth and nose, facial rash ("butterfly rash"), unusual sensitivity to sunlight (photosensitivity), inflammation of the lining that surrounds the lungs (pleuritis) and the heart (pericarditis), and poor circulation to the fingers and toes with cold exposure (Raynaud's phenomenon). Complications of organ involvement can lead to further symptoms that depend on the organ affected and severity of the disease.

Skin manifestations are frequent in lupus and can sometimes lead to scarring. In discoid lupus, only the skin is typically involved. The skin rash in discoid lupus often is found on the face and scalp. It usually is red and may have raised borders. Discoid lupus rashes are usually painless and do not itch, but scarring can cause permanent hair loss. Over time, 5%-10% of patients with discoid lupus may develop SLE.

Over half of the patients with SLE develop a characteristic red, flat facial rash over the bridge of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by worsening of inflammation throughout the body, called a "flare" of the disease.

Typically, this rash can heal without permanent scarring with treatment.

Most patients with SLE will develop arthritis during the course of their illness. Arthritis in SLE commonly involves swelling, pain, stiffness, and even deformity of the small joints of the hands, wrists, and feet. Sometimes, the arthritis of SLE can mimic that of rheumatoid arthritis (another autoimmune disease).

More serious organ involvement with inflammation occurs in the brain, liver, and kidneys. White blood cells and blood-clotting factors also can be characteristically decreased in SLE, known as leucopenia and thrombocytopenia, respectively. Leucopenia can increase the risk of infection and thrombocytopenia can increase the risk of bleeding.

Inflammation of muscles (myositis) can cause muscle pain and weakness. This can lead to elevations of muscle enzyme levels in the blood.

Inflammation of blood vessels (vasculitis) that supply oxygen to tissues can cause isolated injury to a nerve, the skin, or an internal organ. The blood vessels are composed of arteries that pass oxygen-rich blood to the tissues of the body and veins that return oxygen-depleted blood from the tissues to the lungs. Vasculitis is characterized by inflammation with damage to the walls of various blood vessels. The damage blocks the circulation of blood through the vessels and can cause injury to the tissues that are supplied with oxygen by these vessels.

Inflammation of the lining of the lungs (pleuritis) and of the heart (pericarditis) can cause sharp chest pain. The chest pain is aggravated by coughing, deep breathing, and certain changes in body position. The heart muscle itself rarely can become inflamed (carditis). It has also been shown that young women with SLE have a significantly increased risk of heart attacks from coronary artery disease.

Kidney inflammation in SLE can cause leakage of protein into the urine, fluid retention, high blood pressure, and even kidney failure. This can lead to further fatigue and swelling of the legs and feet. With kidney failure, machines are needed to cleanse the blood of accumulated poisons in a process called dialysis.

Involvement of the brain can cause personality changes, thought disorders (psychosis), seizures, and even coma. Damage to nerves can cause numbness, tingling, and weakness of the involved body parts or extremities. Brain involvement is referred to as lupus cerebritis.

Many patients with SLE experience hair loss (alopecia). Often, this occurs simultaneously with an increase in the activity of their disease. The hair loss can be patchy or diffuse and appear to be more like hair thinning.

Some patients with SLE have Raynaud's phenomenon. In these patients, the blood supply to the fingers and/or toes becomes compromised upon exposure to cold, causing blanching, whitish and/or bluish discoloration, and pain and numbness in the exposed fingers and toes.

How is lupus diagnosed?

Since patients with SLE can have a wide variety of symptoms and different combinations of organ involvement, no single test establishes the diagnosis of systemic lupus. To help doctors improve the accuracy of the diagnosis of SLE, 11 criteria were established by the American Rheumatism Association. These 11 criteria are closely related to the symptoms discussed above. Some patients suspected of having SLE may never develop enough criteria for a definite diagnosis. Other patients accumulate enough criteria only after months or years of observation. When a person has four or more of these criteria, the diagnosis of SLE is strongly suggested. Nevertheless, the diagnosis of SLE may be made in some settings in patients with only a few of these classical criteria, and treatment may sometimes be instituted at this stage. Of these patients with minimal criteria, some may later develop other criteria, but many never do.

The 11 criteria used for diagnosing systemic lupus erythematosus are

malar (over the cheeks of the face) "butterfly" rash,

discoid skin rash (patchy redness with hyperpigmentation and hypopigmentation that can cause scarring

photosensitivity (skin rash in reaction to sunlight [ultraviolet light] exposure

mucous membrane ulcers (spontaneous ulcers of the lining of the mouth, nose, or throat

arthritis (two or more swollen, tender joints of the extremities

pleuritis or pericarditis (inflammation of the lining tissue around the heart or lungs, usually associated with chest pain upon breathing or changes of body position

kidney abnormalities (abnormal amounts of urine protein or clumps of cellular elements called casts detectable with a urinalysis

brain irritation (manifested by seizures [convulsions] and/or psychosis),

blood-count abnormalities (low counts of white or red blood cells, or platelets, on routine blood testing

immunologic disorder (abnormal immune tests include anti-DNA or anti-Sm [Smith] antibodies, falsely positive blood test for syphilis, anticardiolipin antibodies, lupus anticoagulant, or positive LE prep test), and

antinuclear antibody (positive ANA antibody testing [antinuclear antibodies in the blood]).

In addition to the 11 criteria, other tests can be helpful in evaluating patients with SLE to determine the severity of organ involvement. These include routine testing of the blood to detect inflammation (for example, tests called the sedimentation rate and C-reactive protein), blood-chemistry testing, direct analysis of internal body fluids, and tissue biopsies. Abnormalities in body fluids and tissue samples (kidney, skin, and nerve biopsies) can further support the diagnosis of SLE. The appropriate testing procedures are selected for the patient individually by the doctor.

What is the treatment for systemic lupus?

There is no permanent cure for SLE. The goal of treatment is to relieve symptoms and protect organs by decreasing inflammation and/or the level of autoimmune activity in the body. Many patients with mild symptoms may need no treatment or only intermittent courses of antiinflammatory medications. Those with more serious illness involving damage to internal organ(s) may require high doses of corticosteroids in combination with other medications that suppress the body's immune system.

Patients with SLE need more rest during periods of active disease. Researchers have reported that poor sleep quality was a significant factor in developing fatigue in patients with SLE. These reports emphasize the importance for patients and physicians to address sleep quality and the effect of underlying depression, lack of exercise, and self-care coping strategies on overall health. During these periods, carefully prescribed exercise is still important to maintain muscle tone and range of motion in the joints.

Nonsteroidal antiinflammatory drugs (NSAIDs) are helpful in reducing inflammation and pain in muscles, joints, and other tissues. Examples of NSAIDs include aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and sulindac (Clinoril). Since the individual response to

NSAIDs varies among patients, it is common for a doctor to try different NSAIDs to find the most effective one with the fewest side effects. The most common side effects are stomach upset, abdominal pain, ulcers, and even ulcer bleeding. NSAIDs are usually taken with food to reduce side effects. Sometimes, medications that prevent ulcers while taking NSAIDs, such as misoprostol (Cytotec), are given simultaneously.

Corticosteroids are more potent than NSAIDs in reducing inflammation and restoring function when the disease is active. Corticosteroids are particularly helpful when internal organs are affected. Corticosteroids can be given by mouth, injected directly into the joints and other tissues, or administered intravenously. Unfortunately, corticosteroids have serious side effects when given in high doses over prolonged periods, and the doctor will try to monitor the activity of the disease in order to use the lowest doses that are safe. Side effects of corticosteroids include weight gain, thinning of the bones and skin, infection, diabetes, facial puffiness, cataracts, and death (necrosis) of the tissues in large joints.

Hydroxychloroquine (Plaquenil) is an antimalarial medication found to be particularly effective for SLE patients with fatigue, skin involvement, and joint disease. Consistently taking Plaquenil can prevent flare-ups of lupus. Side effects are uncommon but include diarrhea, upset stomach, and eye-pigment changes. Eye-pigment changes are rare but require monitoring by an ophthalmologist (eye specialist) during treatment with Plaquenil. Researchers have found that Plaquenil significantly decreased the frequency of abnormal blood clots in patients with systemic lupus. Moreover, the effect seemed independent of immune suppression, implying that Plaquenil can directly act to prevent the blood clots. This fascinating study highlights an important reason for patients and doctors to consider Plaquenil for long-term use, especially for those SLE patients who are at some risk for blood clots in veins and arteries, such as those with phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant, and false-positive venereal disease research laboratory test). This means not only that Plaquenil reduces the chance for re-flares of SLE, but it can also be beneficial in thinning the blood to prevent abnormal excessive blood clotting. Plaquenil is commonly used in combination with other treatments for lupus.

For resistant skin disease, other antimalarial drugs, such as chloroquine (Aralen) or quinacrine, are considered and can be used in combination with hydroxychloroquine. Alternative medications for skin disease include dapsone and retinoic acid (Retin-A). Retin-A is often effective for an uncommon wart-like form of lupus skin disease. For more severe skin disease, immunosuppressive medications are considered as described below.

Medications that suppress immunity (immunosuppressive medications) are also called cytotoxic drugs. Immunosuppressive medications are used for treating patients with more severe manifestations of SLE, such as damage to internal organ(s). Examples of immunosuppressive medications include methotrexate (Rheumatrex, Trexall), azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine (Sandimmune). All immunosuppressive medications can seriously depress

blood-cell counts and increase risks of infection and bleeding. Other side effects are specific for each drug. For examples, Rheumatrex can cause liver toxicity, while Sandimmune can impair kidney function.

In recent years, mycophenolate mofetil (Cellcept) has been used as an effective medication for lupus, particularly when it is associated with kidney disease. Cellcept has been helpful in reversing active lupus kidney disease (lupus renal disease) and in maintaining remission after it is established. Its lower side-effect profile has advantage over traditional immune-suppression medications.

In SLE patients with serious brain or kidney disease, plasmapheresis is sometimes used to remove antibodies and other immune substances from the blood to suppress immunity. Rarely, SLE patients can develop seriously low platelet levels, thereby increasing the risk of excessive and spontaneous bleeding. Since the spleen is believed to be the major site of platelet destruction, surgical removal of the spleen is sometimes performed to improve platelet levels. Other treatments have included plasmapheresis and the use of male hormones. Plasmapheresis has also been used to remove proteins (cryoglobulins) that can lead to vasculitis. End-stage kidney damage from SLE requires dialysis and/or a kidney transplant.

Most recent research is indicating benefits of rituximab (Rituxan) in treating lupus. Rituximab is an intravenously infused antibody that suppresses a particular white blood cell, the B cell, by decreasing their number in the circulation. B cells have been found to play a central role in lupus activity, and when they are suppressed, the disease tends toward remission. This may particularly helpful for patients with kidney disease.

At the 2007 national Rheumatology meeting, there was a paper presented suggesting that low-dose dietary supplementation with omega-3 fish oils could help patients with lupus by decreasing disease activity and possibly decreasing heart-disease risk.

Systemic Lupus (cont.)

In this Article What is lupus? What are the types of lupus? What causes lupus? Is it hereditary? What is drug-induced lupus? What are the symptoms and signs of lupus? How is lupus diagnosed? What is the treatment for systemic lupus? How can a lupus patient help prevent disease activity (flares)? How can lupus affect pregnancy or the newborn? What does the future hold for patients with lupus? Where can one get more information about lupus? Systemic Lupus At A Glance Patient Discussions: Lupus - Symptoms at Onset of Disease Systemic Lupus Glossary

Systemic Lupus Index

What does the future hold for patients with lupus?

Overall, the outlook for patients with systemic lupus is improving each decade with the development of more accurate monitoring tests and treatments.

The role of the immune system in causing diseases is becoming better understood through research. This knowledge will be applied to design safer and more effective treatment methods. For example, completely revising the immune system of patients with extremely aggressive treatments that virtually temporarily wipe out the immune system is being evaluated. Current studies involve immune eradication with or without replacement of cells that can re-establish the immune system (stem cell transplantation).

It should be noted that patients with SLE are at a somewhat increased risk for developing cancer. The cancer risk is most dramatic for blood cancers, such as leukemia and lymphoma, but is also increased for breast cancer. This risk probably relates, in part, to the altered immune system that is characteristic of SLE.

Women with SLE appear to be at increased risk for heart disease (coronary artery disease) according to recent reports. Women with SLE should be evaluated and counseled to minimize risk factors for heart disease, such as elevated blood cholesterol, quitting smoking, high blood pressure, and obesity.

DHEA (dehydroepiandrosterone) has been helpful in reducing fatigue, improving thinking difficulties, and improving quality of life in patients with SLE. Recent research indicates that DHEA has been shown to improve or stabilize signs and symptoms of SLE. DHEA is commonly available in health-food stores, pharmacies, and many groceries.

Landmark research has shown clearly that oral contraceptives do not increase the rate of flares of systemic lupus erythematosus. This important finding is opposite to what has been thought for years. Now we can reassure women with lupus that if they take birth-control pills, they are not increasing their risk for lupus flares. NOTE: Birth-control pills or any estrogen medications should still be avoided by women who are at increased risk of blood clotting, such as women with lupus who have phospholipid antibodies (including cardiolipin antibody and lupus anticoagulant).

Individuals with SLE can improve their prognosis by learning about the many aspects of the illness as wWhat are antinuclear antibodies?

We normally have antibodies in our blood that repel invaders into our body, such as virus and bacteria microbes. Antinuclear antibodies (ANAs) are unusual antibodies, detectable in the blood, that have the capability of binding to certain structures within the nucleus of the cells. The nucleus is the innermost core within the body's cells and contains the DNA,

the primary genetic material. ANAs are found in patients whose immune system may be predisposed to cause inflammation against their own body tissues. Antibodies that are directed against one's own tissues are referred to as auto-antibodies. The propensity for the immune system to work against its own body is referred to as autoimmunity. ANAs indicate the possible presence of autoimmunity and provide, therefore, an indication for doctors to consider the possibility of autoimmune illness.

How is the ANA test designed? What is it for?

The ANA test was designed by Dr. George Friou in 1957. The ANA test is performed using a blood sample. The antibodies in the serum of the blood are exposed in the laboratory to cells. It is then determined whether or not antibodies are present that react to various parts of the nucleus of cells. Thus, the term anti-"nuclear" antibody. Fluorescence techniques are frequently used to actually detect the antibodies in the cells, thus ANA testing is sometimes referred to as fluorescent antinuclear antibody test (FANA). The ANA test is a sensitive screening test used to detect autoimmune diseases

ell as closely monitoring their own health with their doctors.

What are autoimmune diseases?

Autoimmune diseases are conditions in which there is a disorder of the immune system characterized by the abnormal production of antibodies (auto-antibodies) directed against the tissues of the body. Autoimmune diseases typically feature inflammation of various tissues of the body. ANAs are found in patients with a number of different autoimmune diseases, such as systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, polymyositis, scleroderma, Hashimoto's thyroiditis, juvenile diabetes mellitus, Addison disease, vitiligo, pernicious anemia, glomerulonephritis, and pulmonary fibrosis. ANAs can also be found in patients with conditions that are not considered classic autoimmune diseases, such as chronic infections and cancer.

What other conditions cause ANAs to be produced?

ANAs can be produced in patients with infections (virus or bacteria), lung diseases (primary pulmonary fibrosis, pulmonary hypertension), gastrointestinal diseases (ulcerative colitis, Crohn's disease, primary biliary cirrhosis, alcoholic liver disease), hormonal diseases (Hashimoto's autoimmune thyroiditis, Grave's disease), blood diseases (idiopathic thrombocytopenic purpura, hemolytic anemia), cancers (melanoma, breast, lung, kidney, ovarian and others), skin diseases (psoriasis, pemphigus), as well as in the elderly and those people with a family history of rheumatic diseases.

Can medications cause ANAs to be produced?

Many medications can sometimes stimulate the production of ANAs, including procainamide (Procan SR), hydralazine, and dilantin. ANAs that are stimulated by medication are referred to as drug-induced ANAs. This does not necessary mean that any disease is present when these ANAs are "induced." Sometimes diseases are associated with these ANAs, and they are referred to as drug-induced diseases.

ANAs are defined in certain patterns. What does this mean?

ANAs present different "patterns" depending on the staining of the cell nucleus in the laboratory: homogeneous or diffuse; speckled; nucleolar; and peripheral or rim. While these patterns are not specific for any one illness, certain illnesses can more frequently be associated with one pattern or another. The patterns then can sometimes give the doctor further clues as to types of illnesses to look for in evaluating a patient. For example, the nucleolar pattern is more commonly seen in the disease scleroderma. The speckled pattern is seen in many conditions and in people who do not have any autoimmune disease.

Are ANAs always associated with illness?

No. ANAs can be found in approximately 5% of the normal population, usually in low titers (low levels). These people usually have no disease. Titers of lower than 1:80 are less likely to be significant. (ANA titers of less than or equal to 1:40 are considered negative.) Even higher titers are often insignificant in patients over 60 years of age. Ultimately, the ANA result must be interpreted in the specific context of an individual patient's symptoms and other test results. It may or may not be significant in a given individual.