Anti-Endomysium Antibodies (EMA) Present In Blood

What Are Anti-Endomysium Antibodies?

[dropcap]A[/dropcap]nti-endomysium antibodies (EmA) are connective tissue autoantibodies produced in persons who have inherited the genes for celiac disease, an autoimmune disease, and are reacting to gluten in their diet.

Autoantibodies are abnormal in that they attack the body’s own tissue.

Q: What is endomysium?

A: Endomysium is the delicate connective tissue that surrounds individual muscle fibers. The autoantigen, or target, that stimulates the autoimmune response is the naturally occuring enzyme in endomysium called tissue transglutaminase (tTG), or more specifically tranglutaminase-2 (TG2). Anti-tissue transglutaminase antibodies recognize the same antigen as EmA, from which they differ in terms of detection method.

Anti-endomysium antibodies (EmA) are tested by the indirect immunofluorescence method and directed against “reticulin-like” fibres in connective tissue around smooth muscle fibres in the esophagus, liver, stomach, and bladder of monkeys, in the sections of the jejunum and kidneys of rats and in sections of the human umbilical cord. In comparison, for the determination of anti-tissue transglutaminase IgA and IgG antibodies, ELISA with human extractive or recombinant transglutaminase is recommended.¹

EmA‐binding patterns in serum samples from patients with celiac disease have proved to be exclusively TG2‐targeted and the correlation between EmA and TG2 antibodies is therefore good. Evidence shows that celiac autoantibodies are produced in the small‐bowel mucosa.²

What Are Anti-Endomysium Antibodies In Celiac Disease and/or Gluten Sensitivity?

• Relationship between anti-endomysium antibodies and celiac disease. Anti-endomysium antibodies found by blood testing are a classic finding in celiac disease. They are highly sensitive and specific to celiac disease, making their abnormal presence in the blood useful for identifying celiac disease.³ Specific to celiac disease means these antibodies are only produced in celiac disease and not other forms of gluten sensitivity such as non-celiac gluten sensitivity and wheat allergy.

• Relationship between anti-endomysium antibodies and performance compared to anti-tTG testing. A study investigating anti-endomysium (EmA) and anti-tissue transglutaminase IgA (tTG-A) antibodies in celiac disease diagnosis, gluten free diet monitoring, and first degree relatives screening in celiac disease adult patients found that EmA predictive ability for celiac disease diagnosis was slightly better compared to tTG-A (P = 0.043). EmA could assess compliance with gluten free diet already from the beginning of the diet, while both EmA and tTG-A had an equal ability to discriminate between strictly and partially compliant patients after the first semester and during the  3 years of monitoring. Screening of first degree relatives resulted in the identification of 2 undiagnosed celiac disease cases.⁴

• Relationship between anti-endomysium antibodies and active disease. A study investigating the association between serum antibody levels and a subsequent celiac disease diagnosis in a large series of children and adults found that irrespective of the initial blood levels or clinical presentation, EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis. 79% of the subjects with low and 94% of those with high serum EmA titers showed small-bowel mucosal villous atrophy. Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a gluten-containing diet, or responded positively to a gluten-free diet.⁵
• Relationship between anti-endomysium antibodies and diagnosis. The IgA-EmA assay may be especially predictive in populations who have a high prevalence of other causes of flat mucosa seen on intestinal biopsy. In this instance, a biopsy indicating villous atrophy with a positive EmA test would differentiate celiac disease from conditions such as cow’s milk enteropathy and other enteropathies that also produce villous atrophy.
• Relationship between anti-endomysium antibodies and antibody production ability. A negative endomysium antibody test result does not rule out the possibility of celiac disease. For example, patients with I gA deficiency will test negative for IgA-EmA antibodies because they cannot make the IgA type of antibodies that this test relies on detecting.³
• Relationship between anti-endomysium antibodies and false negative test result. A false negative result means that the test fails to detect presence of antibodies in the blood although the patient has celiac disease that is established by other methods. A study  by Salmi and associates suggests that serum EmA negativity might be related to a longlasting, complicated celiac disease. Importantly, TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative celiac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and celiac disease.²

How Prevalent Are Anti-Endomysium Antibodies?

• Celiac disease occurs in 1% of the general population.⁶ A healthy population usually tests negative for anti-endomysium antibodies.⁷
• 100% of study patients with abdominal symptoms had positive anti-endomysium antibodies.⁸

What Are The Symptoms Of Anti-Endomysium Antibodies?

• The presence of anti-endomysium antibodies in blood is marked by positivity to IgA-EMA antibody assay.

How Do Anti-Endomysium Antibodies Develop?

• The presence of anti-endomysium antibodies results from a specific immune response to gluten exposure in susceptible individuals.

Do Anti-Endomysium Antibodies Respond To Gluten-Free Diet?

Yes. A strict gluten free diet results in disappearance of these antibodies, usually diminishing within weeks.⁹

6 Steps To Improve Anti-Endomysium Antibodies In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both EmA antibodies and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.¹⁰
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.¹¹
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.¹¹
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.¹¹.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.¹¹
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.¹¹
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹¹
• Cocoa and Black Tea increase blood sugar.
• Rosemary. Increases blood sugar levels and should not be used by persons with insulin resistance or diabetes. [/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Many medications cause nutritional deficiencies that affect the health of persons with celiac disease. Ask your doctor or pharmacist about this possible adverse effect if you are taking medications. Do not stop prescribed medications without supervision.

 [/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination that provides 100% once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion. However, because it increases blood sugar levels, it should not be used by persons with insulin resistance or diabete.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Anti-Endomysium Antibodies?

RESEARCH STUDY SUMMARIES

“Celiac disease in adult patients: specific autoantibodies in the diagnosis, monitoring, and screening.” This study investigating anti-endomysium (EmA) and anti-tissue transglutaminase IgA (tTG-A) antibodies in celiac disease diagnosis, gluten free diet monitoring, and first degree relatives screening in celiac disease adult patients found that EmA predictive ability for celiac disease diagnosis was slightly better compared to tTG-A (P = 0.043). EmA could assess compliance with gluten free diet already from the beginning of the diet, while both EmA and tTG-A had an equal ability to discriminate between strictly and partially compliant patients after the first semester and so on. Screening of first degree relatives resulted in the identification of 2 undiagnosed celiac disease cases.

70 newly diagnosed Greek adult patients, 70 controls, and 47 first degree relatives were tested for the presence of EmA and tTG-A. The celiac disease  patients were monitored during a 3-year period. Both EmA and tTG-A were found to be suitable markers in the celiac disease  diagnosis, in the screening of celiac disease  among first degree relatives, having also an equal performance in the long term monitoring.⁴

“Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation.” This study investigating the association between serum antibody levels and a subsequent celiac disease diagnosis in a large series of children and adults found that irrespective of the initial serum levels or clinical presentation, EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis.

Besides subjects with classical gastrointestinal presentation of celiac disease, the study cohort included a substantial number of individuals with extraintestinal symptoms and those found by screening in at-risk groups. Altogether 405 patients underwent clinical, serological and histological evaluations. After collection of data, the antibody values were further graded as low [endomysial (EmA) 1:5-200, transglutaminase 2antibodies (TG2-ab) 5.0-30.0 U/L] and high (EmA 1: more than 500, TG2-ab more than 30.0 U/L), and the serological results were compared with the small intestinal mucosal histology and clinical presentation.

In total, 79% of the subjects with low and 94% of those with high serum EmA titers showed small-bowel mucosal villous atrophy. Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a gluten-containing diet, or responded positively to a gluten-free diet.⁵

“Endomysial antibody‐negative celiac disease: clinical characteristics and intestinal autoantibody deposits.” This study evaluating the clinical and histological features (biopsy) of EMA-negative celiac disease and to examine whether EMA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum found that negative serum EMA might be associated with advanced celiac disease.

Serum EmA was studied in 177 biopsy-proved specimens from adult patients with celiac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients.

Results showed 22 patients with IgA-competent celiac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative celiac disease were older, had abdominal symptoms more often, and the density of gammadelta+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with celiac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2.

In conclusion, TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative celiac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and celiac disease.²

“Screening for celiac disease: a prospective study on the value of noninvasive tests.” This study investigating the usefulness of IgG- and IgA- antigliadin antibodies, IgA-endomysial antibodies, and intestinal permeability in diagnosing celiac disease in 102 adult patients with nonspecific abdominal symptoms demonstrated the advantage of IgA-EMA for screening celiac disease. 100% of patients in whom celiac disease was later confirmed by biopsy, had IgA-EMA present except in the case of patients with IgA deficiency or dermatitis herpetiformis. In these patients, the permeability test could improve noninvasive differential diagnosis.⁸

CASE REPORT SUMMARIES

“Pericardial effusion in celiac disease.” This case report describes diagnosis of celiac disease in a 40-year-old woman with progressive fatigue and pitting edema in her lower extremities. Iron deficiency anemia and celiac disease were diagnosed on the basis of low serum ferritin, elevated serum level of IgA endomysial and tissue transglutaminase anti-bodies and histologic findings in small bowel biopsies. Pericardial effusion in her evaluation was detected incidentally. Asymptomatic pericardial effusion in this patient was only detectable with imaging.

After starting of gluten free diet and iron supplement fatigue, peripheral edema and pericardial effusion on echocardiography decreased. It should be noted that asymptomatic pericardial effusion may be seen in adults with celiac disease.¹²

“Celiac disease manifested by polyneuropathy and swollen ankles.” This is a case study revealing celiac disease in a 27-year-old male who started to have his ankles swollen during his military service. He was examined at a military hospital where electromyoneurography showed the signs of distal sensory-motor polyneuropathy with axon demyelinization and weak myopathic changes, whereas histopathological examination of gastrocnemius muscle biopsy revealed some mild and nonspecific myopathy. Besides, he was found to have subcutaneous ankle tissue edemas and hypertransaminasemia. Due to these reasons, he was dismissed from the military service and examined at another hospital where bone osteodensitometry revealed low bone mineral density of the spine. However, his medical problems were not resolved and after the second discharge from hospital he was desperately seeing doctors from time to time.

Finally, at our institution he was shown to have celiac disease by positive serology (antitissue transglutaminase and antiendomysial antibodies) and small bowel mucosal histopathological examination, which showed total small bowel villous atrophy. Three months after the initiation of gluten-free diet, his ankle edema disappeared, electromyoneurographic signs of polyneuropathy improved and liver aminotransferases normalized. Good knowledge of celiac disease extraintestinal signs and serologic screening are essential for early recognition and therapy.¹³

Sources:

1. Trigoni E, Tsirogianni A, Pipi E, Mantzaris G, Papasteriades C. Celiac disease in adult patients: specific autoantibodies in the diagnosis, monitoring, and screening. Autoimmune Dis. 2014;2014:623514. doi: 10.1155/2014/623514. [↩]
2. Salmi TT, Collin P, Korponay-Szabó IR, Laurila K, Partanen J, Huhtala H, Király R, Lorand L, Reunala T, Mäki M, Kaukinen K. Endomysial antibody‐negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.Gut. 2006 Dec;55(12):1746-53. [↩] [↩] [↩]
3. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩] [↩]
4. Trigoni E, Tsirogianni A, Pipi E, Mantzaris G, Papasteriades C. Celiac disease in adult patients: specific autoantibodies in the diagnosis, monitoring, and screening. Autoimmune Dis. 2014;2014:623514. doi: 10.1155/2014/623514. [↩] [↩]
5. Kurppa K, Räsänen T, Collin P, Iltanen S, Huhtala H, Ashorn M, Saavalainen P, Haimila K, Partanen J, Mäki M, Kaukinen K. Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation. World J Gastroenterol. 2012 May 28;18(20):2511-6. doi: 10.3748/wjg.v18.i20.2511. [↩] [↩]
6. National Institutes of Health, “National Institutes of Health Consensus Development Conference Statement, Celiac Disease,” August 9, 2004; 1-14. [↩]
7. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
8. Vogelsang H, Genser D, Wyatt J, et al. Screening for celiac disease: a prospective study on the value of noninvasive tests. The American Journal of Gastroenterology. Mar 1995;90(3):394-8. [↩] [↩]
9. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
10. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
11. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
12. Ashrafi F, Darakhshandeh A, Heidarpour M, Tavakoli T, Najafian J. Pericardial effusion in celiac disease. Int J Prev Med. 2014 Mar;5(3):356-9. [↩]
13. Djuric Z, Kamenov B, Katic V. Celiac disease manifested by polyneuropathy and swollen ankles. World J Gastroenterol. 2007 May 14;13(18):2636-8. [↩]