Immunodeficiencies
What are immunodeficiencies?
If you find yourself repeatedly calling in sick with disabling colds, and googling “Why I keep getting sick over and over” or “Why do I keep getting yeast infections?” you may want to get your immune system a thorough check up.
Our immune system is a network of complex systems that creates specialized cells and proteins which protect our bodies from harmful viruses, bacteria, and fungi. If you’re repeatedly battling infections, fatigue, and brain fog, your immune system may be lacking some of these protective cells and proteins.
About 60 to 70 percent of our immune system lies right under the one-cell-layer-thick lining of our gut (small intestine and large intestine). If this surface breaks down, our immune system is activated, and starts reacting to foods, toxins, and bugs in our gut. The IgA antibody protects our digestive tract and respiratory system, while the liver works harder to detoxify our blood.
Other immune system players include:
- IgM: these are the first antibodies created in the fetus and in response to infection
- T-cell: these lymphocyte cells attack foreign invaders
- B-cell: these lymphocyte cells create immunoglobulins
- antibodies: proteins are designed to eliminate specific antigens; IgG is the most common type of antibody
- cytokines: proteins that send information to cells throughout the immune system
- bone marrow: where immune system cells are first created as stem cells
- thymus: where bone marrow stem cells become T-cells
- platelets: clot the blood to heal cuts
An immunodeficiency disorder is a dysfunction of one or more of these components which prevents the immune system from fighting off infections and diseases. Of the 350 documented primary immunodeficiencies, IgA deficiency is the most common, occurring in about 1 in 500 people.1
Why are so many people IgA deficient?
Research has demonstrated that our intestinal microbiome communicates with cells all across our immune system. This cross-talk is crucial. A lack of good gut microbes (dysbiosis) will lead to inflammation and destruction of the gastrointestinal tract, causing autoimmune disease.1
The microbes and the host immune system must maintain a delicate balance to allow the body to defend itself against infection, while still tolerating healthy microbe levels.
Our normal gut flora produces metabolites – like fatty acids and amino acids – which enhance our gut barrier integrity by:
- promoting immune-balancing T cell formation
- modulating the production of pro-inflammatory mediators (i.e.: inhibiting interleukin 17 – a protein that stimulates inflammation)
Autoimmune disease is as complex as the immune system that hosts it, so be sure to consult with an autoimmunity specialist before trying any treatments. To learn more about immunodeficiencies, visit our Vitadox library today.
Immunodeficiency Symptoms
Reoccurring infections are a sign that you may have a compromised immune system. Other potential signs include:
- pneumonia
- eczema
- pinkeye
- sinus infections
- ear infections
- Epstein-Barr virus
- deep skin abscesses
- swollen lymph nodes
- yeast infection
- enlarged spleen
- sepsis
- anemia
- meningitis
- weight loss and delayed growth
Repeat infections can lead to autoimmune disorders, organ or nerve damage, slowed growth, and death.
The following factors also weaken your immune system, potentially stimulating disorders:
- C-section delivery: C section babies have a higher likelihood of asthma, food allergies and hay fever, as they are not exposed to microbes and don’t develop healthy gut flora13
- poor nutrition: if the body doesn’t get enough vitamins and nutrients its can’t battle invader microbes
- alcohol, sugar and tobacco: reduce the white blood cells’ ability to kill germs
- dehydration: our bodies need water to flush out toxins and boost energy levels
- stress: continued stress stimulates the adrenal gland to produce too much cortisol, which causes immune system cells to leave the blood
- insufficient sleep: during sleep your body produces important infection-fighting antibodies
- insufficient exercise: antibodies have been shown to function much slower in people that do not exercise
- too much or too little hygiene: studies have shown that children who are exposed to germs have a stronger immune system; while good hygiene protects adults from infection
- aging: as you age, your body produces less white blood cells
- viruses: like hepatitis C and AIDS
- severe burns: causes serum protein loss through the skin
- nephrotic syndrome: causes your kidneys to remove too-many proteins
- GI tract disorders: cause loss of serum protein
- spleen removal: removing this blood-filtering organ weakens the immune system
Immunodeficiency occurs when the immune system lacks the ability to fight off foreign invaders. Auto-immune disease occurs when the immune system goes against natural bodily functions
Sometimes people with primary immunodeficiency diseases cannot make “good” antibodies to protect against infection but only make “bad” autoantibodies, which then cause autoimmune disease like:
Allergies and Asthma
Asthma affects 25 million Americans, and it’s increasing every day in America. Why? Researchers have found that genetics and environmental factors interact to cause asthma reactions. Along with pollen, mold, and dust, increasing environmental toxins, food additives, altered proteins and chemical dyes in processed foods, as well as antibiotics and medications can all trigger Asthma – the inflammation of the airways and overproduction of mucus that causes shortness of breath. These allergens can also trigger eczema ,
And the National Heart, Lung, and Blood Institute reports that nearly half of Americans with severe asthma do not respond to conventional drugs. Traditional treatments for food, dander, and drugs also suppress the immune system rather than addressing the root cause.
Genetic factors that are potentially triggered by these environmental factors include:
B-cell (antibody or humoral immunity)
The most common type of primary immunodeficiency, these affect B-cells and include:
- selective IgA deficiency: genetically low levels of IgA
- common variable immunodeficiency (CVID): low IgA, IgG, and IgM levels
- X-linked agammaglobulinemia (XLA): a gene mutation causes patients to run out of their birth mother’s antibodies
- transient hypogammaglobulinemia of infancy: an IgG deficiency in infants
T-cell or Cellular Immunity
These conditions affect T-cells and include:
- X-linked lymphoproliferative syndrome: this only affects men, is caused by genetic mutations, and about half of patients have a strong response to the Epstein-Barr virus
- DiGeorge syndrome: deletions in chromosome genes during an infant’s fetal stage causes either the partial or complete loss of T-cell function
- chronic mucocutaneous candidiasis: a hereditary condition that commonly leads to recurring Candida fungal infection
- zeta-associated protein 70 (ZAP-70) deficiency: a gene mutation causes defects in ZAP-70, a protein which signals T-cells
Combination deficiencies
These immune disorders affect both B-cells and T-cells and include:
- severe combined immunodeficiency (SCID): the most common types are caused by a genetic effect on the X chromosome
- Wiskott-Aldrich syndrome: caused by mutations to a gene on the X chromosome that makes eczema infections more likely
- ataxia-telangiectasia: a gene mutation affects the ATM protein, leading to neurodegenerative disorders
Defective Phagocytes
Phagocytes are cells that absorb and consume various pathogens. Immune disorders that affect these include:
- chronic granulomatous disease: this genetically inherited disease causes a lack of phagocytes and a buildup of white blood cells called granulomas
- leukocyte adhesion deficiency: more than one types, these genetic mutations reduce the ability of the adhesive glycoproteins that attach to white blood cells to attack bacteria
- Chédiak-Higashi syndrome: a mutation in a protein affects how effectively phagocytes consume bacteria
Complement Deficiencies
These rarest deficiencies affect the complement system, which is comprised of dozens of infection-fighting proteins. Complement deficiencies include:
- C2 deficiency: increases risk of autoimmune diseases like lupus and repertory infections
- hereditary angioedema: the dysfunction or lack of the C1 inhibitor protein causes rapid swelling throughout the body
- properdin deficiency: increases susceptibility to meningitis
Secondary Immunodeficiencies
Some immunodeficiency disorders are not primary – they have no genetic component. Secondary immune deficiency diseases are stimulated exclusively by these environmental factors:
- immunosuppressive medications
- hormonal imbalances
- nutrient deficiencies
- chronic conditions like diabetes
- radiation
- chemotherapy
- cancer
Examples of secondary immunodeficiencies include:
- HIV/AIDS
- leukemia
- viral hepatitis
- lupus
- rheumatoid arthritis
- inflammatory bowel disease
- diabetes
Immunodeficiency Diagnostics
After reviewing your medical history, your healthcare provider can try detecting an immunodeficiency disorder through these tests:
- blood tests: to detect abnormal levels of immunoglobulin and antibodies, and determine white blood cell and T cell counts
- vaccines: after administering the vaccine, your blood is tested to determine if your body creates antibodies
- genetic testing: this can determine if your condition is genetic
- prenatal testing: if you are pregnant and know that you have an immune disorder, testing samples of the amniotic fluid or the placenta can determine if your developing baby does too
- imaging tests: these can determine the nature of certain infections
Early diagnosis is important for preventing serious complications or even death from immunodeficiencies. One study found that 48% of patients with primary immunodeficiencies were not hospitalized after being diagnosed, as opposed to 70% or patients who reported being hospitalized before being diagnosed.1
Treatments for Immunodeficiency
Immunodeficiency treatment aims to decrease the amount and severity of infections by strengthening your immune system.
As with any medical procedure, results of the following treatments vary from patient to patient, depending on age, genetics, condition severity, as well as environmental and health factors. Consult your healthcare practitioner before embarking on any of these treatment journeys:
Lifestyle Changes
To prevent infections make sure to get proper:
- nutrition: eating a well-balanced diet, avoiding processed sugar, alcohol and caffeine
- sleep: getting at least 8 hours every night
- exercise: getting at least 20 minutes of aerobic exercise daily
- stress management: to reduce cortisol levels that create hormone imbalances
- social support: to help manage emotions and find companionship; one study found that HIV patients in group therapy had a mortality rate of 2.1 per 100 persons-years3
- hygiene and sanitation: wash your hands after using the restroom and before eating; brush and floss teeth daily; clean and bandage cuts promptly
- protected sex
Vitamin and Mineral Supplements
Millions of Americans are deficient in these crucial vitamins and minerals:
- vitamin B6: helps to increase the number of antibodies in your system;4 side effects include sleepiness and a headache
- vitamin B12: a study on animals showed that a lack of this vitamin can decrease the immune system response to viral and bacterial infections;4 side effects include a headache and itching
- vitamin C: helps to strengthen the immune system via the increase of phagocytosis and the movement of neutrophil white blood cells to injury sites;4 side effects include a headache and nausea
- vitamin D: stimulates production of immunoglobulins and cytokines;4 side effects of large doses include fatigue and vomiting
- calcium: acts as a secondary messenger to lymphocyte cells;5 side effects include constipation and gas
- magnesium: plays an important role in the development and activation of the immune system;6 side effects include nausea, bloating, and diarrhea
Acupuncture
Acupuncture can increase red blood cell count and strengthen the immune system, resolving conditions like allergies, and HIV-related peripheral neuropathy.7
Medications
These traditional pharmaceuticals should be a last resort for extreme cases, as they come with some severe side effects and/or resistance:
- antivirals: drug resistance is an emerging threat to the utility of antivirals; long term use can cause kidney failure and low red blood cell count
- antibiotics: should be used sparingly and with caution, as they can cause bacteria to become increasingly antibiotic resistant; the long term use of antibiotics damages the gut microbiota; a single course of antibiotics can disrupt the gut microbiome for a year; these alterations have been associated with life-threatening disorders like cardiovascular disease and certain types of cancer, according to researchers at Tulane University
- interferon: synthetic proteins that interfere with virus production; long term use can cause increased blood pressure, heart rate or stroke as well as severe liver damage
- NSAIDs: reduce pain and inflammation; long term use can increase risk of heart disease
Many of these medications are not just for immunodeficiency patients; research strongly suggests that HIV patients who take the antiretroviral treatment cART have a 96% reduction in transmitting the virus to their partners.9
Immunoglobulin (Ig) Replacement Therapy
If you lack immunoglobulins, they can be replaced with gamma globulin, which is a serum created from blood from thousands of donors. Gamma globulin can be given into a vein (intravenously) or under the skin (subcutaneously). A study involving 13 patients with primary and secondary immunodeficiencies who are treated with subcutaneous IgG replacement therapy found that there was a mean increase of serum IgG levels over six months from 460 ± 146 mg/dL to 943 ± 182 mg/dL.10 Though there was no report of systemic adverse events,10 side effects include muscle, joint, or headaches.
Immunotherapies
Interferon-gamma therapy uses a synthetic type of interferon to treat chronic granulomatous disease. Interferon-gamma has been shown to remove the risk of severe infections in 70% of patients with chronic granulomatous disease.11 It’s administered as an injection, and side effects include symptoms like fever, chills, nausea, dizziness, aces, and confusion.
Growth factors can be administered in order to stimulate the creation of white blood cells. The growth factors G-CSF and GM-CSF are used to treat neutropenia (low white blood cells). Side effects include a build-up of fluid in your heart or lungs and osteopenia.12
Stem Cell Therapy
Stem cells can actually modulate the immune system so that it no longer attacks the body so viciously – or at all. Research demonstrates that stem cells can minimize the pathological effects of the immune system , so the body no longer attacks itself – all while preserving its ability to attack foreign substances and real pathogens.
Stem Cell Transplantation
If your immune system is too damaged or ineffective, a stem cell transplant can be done to replace this tissue with that of a healthy donor. The end goal is to provide your body with a new immune system. A common stem cell transplant used to treat immunodeficiencies is bone marrow transplant.
Patients with primary immunodeficiency undergoing allogeneic hematopoietic cell transplantation have found to have the best outcome if they are either younger than 3.5 months of age or are any age but do not have an active infection. Side effects include chills, nausea, and low blood pressure, and a risk of infections, graft failure, and anemia.
Gene Therapy
This therapy delivers healthy genes to replace abnormal ones via a carrier (vector) like a genetically-modified virus that’s administered intravenously or with an injection.
One such gene therapy that has successfully treated severe combined immune deficiencies (SCID) is haematopoietic stem cell (HSC) gene therapy. Since 2000, 40 patients with adenosine deaminase deficiency (a common form of SCID) were treated with HSC gene therapy and experienced 100% survival and 75% disease-free survival.
These therapies may be very useful at treating conditions like HIV/AIDS. Many therapies are currently being evaluated for safety, as serious side effects of gene therapy include inflammation, infection, low blood pressure, and tumors (if the wrong cells are targeted). To date, the only FDA-approved gene therapy in the U.S. is tisagenlecleucel, which is used to treat lymphoblastic leukemia.
Learn More
A compromised immune system can disrupt your entire family’s quality of life, but there are plenty of immune care options delivered by a wide range of healthcare providers. To learn more about immunodeficiencies and their treatments, visit our Vitadox library today.
Sources:
- Cianci R, Pagliari D, Piccirillo CA, Fritz JH, Gambassi G. The microbiota and immune system crosstalk in health and disease. Mediators Inflamm. 2018;2018:2912539.
- Decroo, Tom, et al. “Four-Year Retention and Risk Factors for Attrition among Members of Community ART Groups in Tete, Mozambique.” Tropical Medicine & International Health, vol. 19, no. 5, 2014, pp. 514–521., doi:10.1111/tmi.12278.
- Aslam, Muhammad Farhan, et al. “Vitamins: Key Role Players in Boosting Up Immune Response-A Mini Review.” Vitamins & Minerals, vol. 06, no. 01, 31 Mar. 2017, doi:10.4172/2376-1318.1000153.
- Vig, Monika, and Jean-Pierre Kinet. “Calcium Signaling in Immune Cells.” Nature Immunology, vol. 10, no. 1, Jan. 2009, pp. 21–27., doi:10.1038/ni.f.220.
- Schmitz, Carsten, and Anne-Laure Perraud. “Magnesium and the Immune Response.” Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals, 2017, pp. 319–331., doi:10.1016/b978-0-12-802168-2.00026-9.
- Dimitrova, Alexandra. “Introducing a Standardized Acupuncture Protocol for Peripheral Neuropathy: A Case Series.” Medical Acupuncture, vol. 29, no. 6, 1 Dec. 2017, pp. 352–365., doi:10.1089/acu.2017.1242.
- Cihlar, Tomas, and Marshall Fordyce. “Current Status and Prospects of HIV Treatment.” Current Opinion in Virology, vol. 18, June 2016, pp. 50–56., doi:10.1016/j.coviro.2016.03.004.
- Koterba, Alan P, and Mark R Stein. “Initiation of Immunoglobulin Therapy by Subcutaneous Administration in Immunodeficiency Patients Naive to Replacement Therapy.” Allergy, Asthma & Clinical Immunology, vol. 10, no. 1, 6 Dec. 2014, doi:10.1186/s13223-014-0063-8.
- Errante, Paolo, et al. “The Use of Interferon-Gamma Therapy in Chronic Granulomatous Disease.” Recent Patents on Anti-Infective Drug Discovery, vol. 3, no. 3, 2008, pp. 225–230., doi:10.2174/157489108786242378.
- Mehta, Hrishikesh M., et al. “G-CSF and GM-CSF in Neutropenia.” The Journal of Immunology, vol. 195, no. 4, 7 Aug. 2015, pp. 1341–1349., doi:10.4049/jimmunol.1500861.
- Pai, Sung-Yun, and Morton J. Cowan. “Stem Cell Transplantation for Primary Immunodeficiency Diseases.” Current Opinion in Allergy and Clinical Immunology, vol. 14, no. 6, Dec. 2014, pp. 521–526., doi:10.1097/aci.0000000000000115.
- Booth, Claire, et al. “Treating Immunodeficiency through HSC Gene Therapy.” Trends in Molecular Medicine, vol. 22, no. 4, 2016, pp. 317–327., doi:10.1016/j.molmed.2016.02.002.
- Neu, Josef, and Jona Rushing. “Cesarean Versus Vaginal Delivery: Long-Term Infant Outcomes and the Hygiene Hypothesis.” Clinics in Perinatology, vol. 38, no. 2, June 2011, pp. 321–331., doi:10.1016/j.clp.2011.03.008.
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