Common Variable Immunodeficiency 

What Is Common Variable Immunodeficiency?

[dropcap]C[/dropcap]ommon variable immunodeficiency (CVID) is a primary antibody deficiency disease characterized by the onset of recurrent bacterial infections resulting from markedly decreased immunoglobulin antibody production and antibody levels.

Q: What causes common variable immunodeficiency?

A: Common variable immunodeficiency is caused by a defect in any critical stage of B cell development and is characterized by impaired production of normal amounts of antigen-specific antibodies. This is a set up for infection, autoimmune disease, and cancer.

One important histologic feature is the absence or paucity of plasma cells in the biopsy that occurs in common variable immunodeficiency. The diagnosis is initially made by measuring quantitative immunoglobulins and then specific immune testing on these cell subsets in the circulation by flow cytometry.¹

Early diagnosis and treatment with IgG therapy (immunoglobulin G) can decrease illness and mortality.² 

Pulmonary damage is the most frequent complication and may result from recurrent infections and/or immune dysregulation. Other complications due to the underlying immune dysregulation include lymphoproliferative disease (granulomatous disease, lymphadenopathy and hepatosplenomegaly), autoimmune disease, gastrointestinal disease such as chronic inflammation and an increased risk of cancer.³

It is important to recognize that common variable immunodeficiency can occur at any age, but an early onset may be associated with an increased risk of gastric cancers and lymphoma, particularly of the intestine.³

Patients with common variable immunodeficiency should be managed by an immunologist with experience in primary immunodeficiency states, given the complications of these patients.⁴

What Is Common Variable Immunodeficiency In Celiac Disease and/or Gluten Sensitivity?

• Common variable immunodeficiency (CVID) is an associated immune disorder in celiac disease.

• CVID patients with associated celiac disease may develop neurological disease including sensory loss, ataxia, and retinitis pigmentosa due to free radical caused neuronal damage induced by vitamin E deficiency.⁵
• All CVID patients with evidence of enteropathy should be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological sequelae.⁶
• Clinicians should be aware of the low sensitivity, or failure to identify celiac disease, of serologic testing in CVID.⁷ 
• 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.⁸

How Prevalent Is Common Variable Immunodeficiency In Celiac Disease and/or Gluten Sensitivity?

Common variable immunodeficiency is frequently associated with subtotal villus atrophy of celiac disease and the association should not be considered fortuitous.⁹

What Are The Symptoms Of Common Variable Immunodeficiency?

Common variable immunodeficiency is marked by these symptoms:

• Recurrent infections. The most common infection among children was pneumonia (62%); followed by suppurative otitis media in 49% of patients.¹⁰
• Neurological disease including sensory loss, ataxia, and retinitis pigmentosa due to free radical mediated nerve damage (vitamin E deficiency).

How Does Common Variable Immunodeficiency Develop In Celiac Disease and/or Gluten Sensitivity?

• Common variable immunodeficiency results from vitamin E deficiency in celiac disease.

Does Common Variable Immunodeficiency Respond To Gluten-Free Diet?

All CVID patients with evidence of enteropathy should be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological sequelae.¹¹

Malabsorption of vitamin E due to celiac disease can be corrected by this diet.

6 Steps To Improve Risk For Common Variable Immunodeficiency 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 immune 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.¹²
• The intestinal lining may take up to a year to heal.[/box]

[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.¹³
• 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.¹³
• 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.¹³.
• 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.¹³
• 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.¹³
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹³[/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 lettuce, kale, 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” ]

Certain prescription drugs deplete vitamin E which promotes common variable immunodeficiency. 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.

CHOLESTEROL DRUGS

• Colestid® and Questran® deplete Vitamin E.

WEIGHT LOSS DRUGS THAT BIND FAT also interfere with absorption of some nutrients.

• Zenicol (Orlistat®) depletes Vitamin E.

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• [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 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.
• Vitamin E as prescribed following blood test for status.

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 Common Variable Immunodeficiency In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Primary antibody deficiencies at Queen Rania Children Hospital in Jordan: single center experience.” This retrospective study investigating the demographic, clinical, immunological features and complications of children diagnosed with primary antibody deficiency at a referral center in Jordan found these autoimmune associations (17%): inflammatory arthritis, discoid lupus, inflammatory bowel disease, vasculitis and celiac disease.

The medical records of pediatric patients who were diagnosed as primary antibody deficiency (PAD) during the period from January 2006 to June 2013 were reviewed. Patients were diagnosed as PADs based on the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiency (ESID) diagnostic criteria.

A total number of 53 patients with PAD were identified; 37 (70%) males and 16(30%) females, 16(30%) patients with congenital agammaglobulinemia, 16(30%) patients with common variable immunodeficiency, 4(7.5%) patients with IgG subclass deficiency, 10(19%) cases with transient hypogammaglobulinemia of infancy and 7(13.5%) patients as undefined PAD. The most common infection among patients was pneumonia (62%); followed by suppurative otitis media in 49% of patients. Cytopenia was the most noted autoimmune association and was found at prevalence of 22 %, other The prevalence of long-term complications was 58%, the most frequent ones were; stunted growth in 13%, bronchiectasis and lymphoproliferation in 11% for each. The awareness of families, general population as well as primary health physicians is crucial in the establishment of early diagnosis and prompt commencement of appropriate therapy for primary antibody disease.¹⁴

CASE REPORT SUMMARIES

“Common variable immunodeficiency and celiac disease.” This report of two cases of common variable immunodeficiency associated with chronic symptoms of malabsorption due to total villous atrophy describes how symptoms of malabsorption disappeared and histological abnormalities improved after a gluten free diet. The association between celiac disease and common variable immunodeficiency should not be considered as fortuitous. Clinicians should be aware of this association and of the low sensitivity of serologic testing in this setting.⁹

Sources:

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2. Maarschalk-Ellerbroek LJ, Hoepelman AI, van Montfrans JM, Ellerbroek PM. The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital. J Clin Immunol. 2012 Oct;32(5):907-21. doi: 10.1007/s10875-012-9671-6. [↩]
3. Maarschalk-Ellerbroek LJ, Hoepelman AI, van Montfrans JM, Ellerbroek PM. The spectrum of disease manifestations in patients with common variable immunodeficiency disorders and partial antibody deficiency in a university hospital. J Clin Immunol. 2012 Oct;32(5):907-21. doi: 10.1007/s10875-012-9671-6. [↩] [↩]
4. Murray JA1, Rubio-Tapia A. Diarrhoea due to small bowel diseases. Best Pract Res Clin Gastroenterol. 2012 Oct;26(5):581-600. doi: 10.1016/j.bpg.2012.11.013. [↩]
5. Aslam A, Misba SA, Talbot K, Chapel H. Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Clinical Immunology. Jul 2004;112(1):24-9. [↩]
6. Aslam A, Misba SA, Talbot K, Chapel H. Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Clinical Immunology. Jul 2004;112(1):24-9. [↩]
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8. 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, Available at: http://www.wjgnet.com/1007-9327/9/1377.asp. Accessed Jan 3, 2005. [↩]
9. Bechade D, Desrame J, De Fuentes G, Camparo P, Raynaud JJ, Algayres JP. Common variable immunodeficiency and celiac disease. Gatroenterologie Clinique et Biologique. Oct 2004;28(10 Pt 1):909-12. [↩] [↩]
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13. 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. [↩] [↩] [↩] [↩] [↩] [↩]
14. Habahbeh ZM, Abu-Shukair ME, Almutereen MA, Alzyoud RM, Wahadneh AM. Primary antibody deficiencies at Queen Rania Children Hospital in Jordan: single center experience. Iran J Immunol. 2014 Mar;11(1):49-58. doi: IJIv11i1A6. [↩]