IgA Deficiency

What Is IgA Deficiency?

[dropcap]I[/dropcap]gA deficiency (IgAD) is an immunodeficiency disease characterized by lack of immunoglobulin A type antibody production, called IgA antibody, with no detectable levels in blood or secretions.

Q: What is an IgA antibody?

A: IgA is an antibody of the immune system that is secreted by plasma cells (specialized white blood cells) through epithelial cell linings of mucosal surfaces into mucosa secretions to protect the lining from microbe invasion.

In fact, immunoglobulin class A is the main protein of the mucosal immune system. This includes mucosa of the eye surface, digestive tract, respiratory tract, urinary tract, and genital tract.

Both major histocompatibility complex (MHC) and non-MHC genes contribute to susceptibility to the disease. The former genes appear to be located in different parts of the MHC region depending on the HLA haplotype. The latter show a marked overlap with genes associated with a variety of autoimmune disorders including Graves’ disease, systemic lupus erythematosus, type 1 diabetes and celiac disease, suggesting common pathophysiological mechanisms. The involvement of genes associated with autoimmunity may suggest that IgAD in itself is an autoimmune disease.¹

IgA deficiency may progress into a common variable immunodeficiency (CVID).²

What Is IgA Deficiency (IgAD) In Celiac Disease and/or Gluten Sensitivity?

• IgA deficiency is an associated immune disorder in celiac disease characterized by the marked absence of IgA antibodies to endomysium, transglutaminase, and gliadin. The usual blood tests that are used to identify celiac disease measure the levels of antibodies to these antigens as follows:

• IgA autoantibodies produced against endomysium, a connective tissue in muscle, are called anti-endomysial antibodies, or IgA EMA.
• IgA autoantibodies produced against tranglutaminase, an enzyme, are called anti-tissue transglutaminase, or IgA tTG.
• IgA antibodies produced against gliadin, the protein in wheat that is toxic to people with celiac disease, are called  anti-gliadin, or IgA AGA.
• IgA antibodies produced against deamidated gliadin peptides (DGP) are called IgA anti-DGP.
• At the same time, the presence of IgG class antibody levels is high.

• Therefore, IgA deficiency may be a potential source of false-negative results on tests for IgA antibodies in patients being tested for celiac disease because they cannot identify celiac disease.³
• The association between celiac disease and other immune disorders may be due to the sharing of a common genetic background, such as HLA antigens. However, in a very large study, involving 909 patients with celiac disease, Ventura and his associates found that the development of immune disorders in celiac disease was clearly related to the duration of exposure to gluten.⁴

How Prevalent Is IgA Deficiency In Celiac Disease and/or Gluten Sensitivity?

• IgA deficiency is frequently associated with celiac disease.⁵
• The prevalance of selective immunoglobulin (Ig) A deficiency was 9.1% in a study of 109 children with celiac disease  at diagnosis.⁶.

What Are The Symptoms Of IgA Deficiency?

Although most patients are asymptomatic, IgA deficiency can show these symptoms:

• Recurrent infections.
• Chronic diarrhea.
• Allergy or autoimmune disease.

How Does IgA Deficiency Develop In Celiac Disease and/or Gluten Sensitivity?

• IgA deficiency results from same genetic background as celiac disease.⁷

Does IgA Deficiency Respond To Gluten-Free Diet?

Of plasma cytokine levels, only IL-10 shows a significant decrease after gluten free diet.⁸

6 Steps To Improve IgA Deficiency 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 IgA deficiency 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.⁹
• 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.¹⁰
• 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.¹⁰
• 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.¹⁰.
• 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.¹⁰
• 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.¹⁰
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹⁰[/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:

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Antibiotic medications are used both to treat respiratory infections and as prophylaxis to prevent infections because of the increased occurrence and susceptibility in IgA deficiency. Antibiotics deplete nutrients. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

 This is not a complete listing.

ANTIBIOTICS disrupt intestinal permeability which complicates celiac disease.

• Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete B Vitamins, Vitamin K, Probiotics, Vitamin C.
• Tetracyclines deplete Coenzyme Q10, Calcium, Magnesium, Iron, Vitamin B6, Zinc, Probiotics, Riboflavin.
• Cipro depletes Coenzyme Q10, Zinc.
• Dapsone depletes vitamin K.

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

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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.
• Calcium citrate is the best absorbed of calcium supplements. Calcium carbonate is a poor choice.
• Vitamin D3 as prescribed following blood test for status.
• Chelated magnesium  as prescribed but do not take at same time as calcium because they compete for absorption.

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.
• 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 IgA Deficiency In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Celiac disease in children with atopic dermatitis.” This study investigating the prevalence of celiac disease in Estonian children with atopic dermatitis (AD), a common multifactorial chronic inflammatory skin disease, detected IgA deficiency in nine patients with AD (2.6%), none of whom had IgG-anti-TG2 or IgG-anti-DGP seropositivity.

351 consecutive children with active AD (mean age 5.8 yrs, 57.6% boys) were recruited at Tallinn Children’s Hospital, Estonia. Sera of all patients were tested for total serum immunoglobulin (Ig) A, for IgA- and IgG-type autoantibodies to tissue transglutaminase (IgA-anti-TG2, IgG-anti-TG2) and to deamidated gliadin peptides (IgA-anti-DGP, IgG-anti-DGP). The diagnosis of celiac disease was confirmed histologically by small intestine biopsy in five (1.4%) patients with AD and all were histologically characterized as Marsh IIIa-IIIc stages and two presented with silent celiac disease.¹¹

“Celiac Disease: Presentation of 109 Children.” This retrospective study investigating clinical and laboratory features of 109 patients with celiac disease found that the prevalance of selective immunoglobulin (Ig) A deficiency was 9.1%. Of 109 patients with celiac disease, 66 (60.6%) were classical type, 41 (37.6%) were atypical type and 2 (1.8%) were silent type. The mean age was 8.81 ± 4.63 years and the most common symptom was diarrhea (53.2%) followed by failure to thrive, short stature, and abdominal pain. Paleness (40.4%), underweight (34.8%), and short stature (31.2%) were the most common findings.

Iron deficiency anemia (81.6%), zinc deficiency (64.1%), prolonged prothrombin time (35.8%), and elevated transaminase levels (24.7%) were the most common laboratory findings. Eight percent of patients had at least 1 autoantibody. Abdominal distention, iron deficiency, prolonged prothrombin time, hypoalbuminemia, and elevated transaminase levels were more significantly frequent in the classical type than atypical type.¹²

“Immunoglobulin G (IgG) anti-tissue transglutaminase antibodies used as markers for IgA-deficient celiac disease patients.” This study investigating the utility of IgG-tTG (antitransglutaminase antibody test) for the detection of untreated celiac disease in IgA-deficient patients demonstrated that IgG-tTG detection with recombinant human tTG is a good alternative to IgG-EMA detection, and the addition of IgG-tTG assessment to the present screening methods may improve the ability to identify IgA-deficient patients with celiac disease.

The overall concordance of the positive and negative results between IgG-tTG and IgG-EMA was 97%, and the IgG-tTG assay discriminated between IgG-EMA-positive and -negative subjects with IgA-deficiency at a rate of 100%.¹³

“Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency.” This study investigating both type 1 and type 2 plasma cytokine levels in celiac disease and in celiac disease-IgA deficiency demonstrated that celiac disease and especially celiac disease-IgA deficienct patients display persistently higher pro-inflammatory cytokine levels, suggesting a persistent state of activation of pro-phlogistic signals in celiac disease, particularly when IgA deficiency coexists.

IL-10 had significantly higher plasma levels in celiac disease-IgA deficiency but not in celiac disease with a significant decrease after a gluten free diet. “Serial measurement of serum IL-10 may be an adjunctive evaluating criterion in the follow-up of celiac disease-IgA deficienct patients.”⁷

Sources:

1. Wang N, Hammarström L. IgA deficiency: what is new? Curr Opin Allergy Clin Immunol. 2012 Dec;12(6):602-8. doi: 10.1097/ACI.0b013e3283594219. [↩]
2. Binek A, Jarosz-Chobot P.Selective immunoglobulin A deficiency. Pediatr Endocrinol Diabetes Metab. 2012;18(2):76-8. [↩]
3. Dahlbom I, Olsson M, Forooz NK, Sjoholm AG, Truedsson L, Hansson T. Immunoglobulin G (IgG) anti-tissue transglutaminase antibodies used as markers for IgA-deficient celiac disease patients. Clinical and Diagnostic Laboratory Immunology. Feb 2005;12(2):254-8. [↩]
4. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G. Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol. 2003;9(6):1377-1380. [↩]
5. Cataldo F, Lio D, Marino V, Scola L, Crivello A, Corazza GR. Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency. Pediatric Allergy Immunology. Aug 2003;14(4):320-4. [↩]
6. Kuloğlu Z, Kirsaçlioğlu CT, Kansu A, Ensari A, Girgin N. Celiac Disease: Presentation of 109 Children. Yonsei Med J. 2009 October 31; 50(5): 617–623. [↩]
7. Cataldo F, Lio D, Marino V, Scola L, Crivello A, Corazza GR. Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency. Pediatric Allergy Immunology. Aug 2003;14(4):320-4. [↩] [↩]
8. Cataldo F, Lio D, Marino V, Scola L, Crivello A, Corazza GR. Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency. Pediatric Allergy Immunology. Aug 2003;14(4):320-4. [↩]
9. 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. [↩]
10. 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. [↩] [↩] [↩] [↩] [↩] [↩]
11. Ress K, Annus T, Putnik U, Luts K, Uibo R, Uibo O. Celiac disease in children with atopic dermatitis. Pediatr Dermatol. 2014 Jul-Aug;31(4):483-8. doi: 10.1111/pde.12372. [↩]
12. Kuloğlu Z, Kirsaçlioğlu CT, Kansu A, Ensari A, Girgin N. Celiac Disease: Presentation of 109 Children. Yonsei Med J. 2009 October 31; 50(5): 617–623. [↩]
13. Dahlbom I, Olsson M, Forooz NK, Sjoholm AG, Truedsson L, Hansson T. Immunoglobulin G (IgG) anti-tissue transglutaminase antibodies used as markers for IgA-deficient celiac disease patients. Clinical and Diagnostic Laboratory Immunology. Feb 2005;12(2):254-8. [↩]