Immunoglobulin A is the first line of defense against harmful microbes, but it is also important for maintaining immune tolerance. Low levels increase the risk of allergies and autoimmune disease. This is the dominant antibody in our gut, respiratory mucus, breast milk, and other secreted fluids. Read on to find out what it means to have low or high IgA levels and which factors can decrease or increase them.
What Is IgA?
IgA is one of the five immunoglobulin classes (in addition to IgG, IgM, IgD, and IgE) [R].
- Gut mucus (intestinal barrier)
- Respiratory mucus
- Urogenital mucus
Circulating IgA is in monomeric form, whereas secretory IgA, in the mucosal secretions of respiratory, intestinal, and genitourinary systems, is dimeric (in the form of two joined IgA monomers) [R].
Mucosal barriers (where IgA is present) separate the interior of the body from the outside world. At these sites, IgA maintains a balanced immune response. It defends against harmful microbes but also prevents reactions against good bacteria and environmental proteins (such as food antigens) [R].
IgA has many important functions:
- It is the first line of defense against harmful microbes [R, R].
- It removes microbes that have breached the epithelial barrier (such as the intestinal barrier) [R].
- It can neutralize toxins and viruses [R, R, R].
- It shapes the composition of the gut microbiota [R, R].
- It neutralizes inflammatory products from microbes [R, R].
- IgA from mother’s milk helps program the infant immune system by regulating their microbiota and protecting them from pathogens [R].
- It helps maintain immune tolerance at mucosal barriers by dampening immune responses against good bacteria and food components [R].
Normal IgA Levels
Normal IgA levels vary slightly depending on the laboratory used to test them. They gradually increase with age and weight in children until they reach stable levels in adults. Blood IgA levels are higher in males than in females [R].
These are the approximate values for IgA depending on age:
- 0-1 years: 1-83 mg/dL
- 1-5 years: 20-152 mg/dL
- 5-10 years: 33-274 mg/dL
- 10-17 years: 42-378 mg/dL
- Older than 18 years: 60-400 mg/dL
Low IgA can be found in individuals with:
- Chronic gut disorders (IBS, IBD) [R, R]
- Food and respiratory allergies [R, R]
- Autoimmune disease (celiac disease, type 1 diabetes) [R]
- Some infections, such as Epstein-Barr virus infection [R]
- Rare disorders such as hereditary telangiectasia [R]
- Some tumors [R, R]
It can be inherited or it can also occur spontaneously (due to infections, medication, or unknown causes) [R].
People are IgA deficient if they have blood IgA levels below 7 mg/dL with normal IgM and IgG levels [R].
High IgA can indicate chronic inflammation or an infection.
IgA is also elevated in individuals with:
- Liver damage [R, R]
- IBD (can also be decreased) [R]
- Some rare diseases and tumors [R, R, R]
- IgA nephropathy [R]
- After heart infarction [R]
Low Levels of Immunoglobulin A Increase the Risk of Allergies and Asthma
IgA protects against allergies.
IgA levels are reduced in children with allergic rhinitis. Lower levels were associated with more severe symptoms [R].
IgA in breast milk may protect against atopic dermatitis in infants. IgA ingested in breast milk during the first year of life reduced the risk of atopic dermatitis up to age 4 [R].
Furthermore, higher levels of IgA in infants protected them from developing allergies at the age of 4 [R].
High IgA levels in saliva were associated with less allergic symptoms in children [R].
In patients allergic to cow’s milk, those who naturally developed tolerance had increased blood IgA levels [R].
Low IgA levels were found in the lungs of severe asthmatics. Lower IgA levels were associated with more severe symptoms [R].
However, in severe asthma, IgA may aggravate the existing inflammation instead of promoting tolerance [R].
Low Immunoglobulin A Increase the Risk of Infections
IgA protects the lungs and the gut against invading harmful microbes.
People with IgA deficiency are at a higher risk for infections, including infections of the respiratory system, gut, joints, and urinary tract [R].
Immunoglobulin A Deficiency Increases the Risk of Autoimmune Diseases
Patients with selective IgA deficiency (undetectable IgA but normal IgG and IgM levels) have a 10 to 20 times higher risk of celiac disease [R].
People with IgA deficiency have a higher risk of type 1 diabetes (up to 10 times), lupus, juvenile idiopathic arthritis, IBD (both Crohn’s and ulcerative colitis), rheumatoid arthritis, and thyroid disorders [R].
Immunoglobulin A Is Decreased in IBS Patients
In a pilot study with 12 IBS patients and 11 healthy controls, those with IBS had less IgA-producing cells [R].
Immunoglobulin A May Be Decreased in IBD Patients
Low IgA has been found in up to 8% of IBD patients [R].
However, higher IgA production in the gut may cause IBD [R].
Bacteria coated with a high level of IgA may be responsible for gut inflammation in patients with IBD. IgA-coated bacteria increase gut inflammation when transplanted into mice with ulcerative colitis [R].
Immunoglobulin A Is Decreased in Depression
Medication-free patients with major depression had a significant reduction in blood IgA levels in the remitted state (when they were symptom-free) [R].
Even in healthy people, IgA was reduced when participants recalled events that made them depressed [R].
Immunoglobulin A May Be Decreased in Autism
Autism is more prevalent among IgA deficient subjects and their relatives [R].
A study showed an association between autism with low normal IgA (<97 mg/dL) [R].
However, another study did not find lower IgA levels in autistic people [R].
Increased Immunoglobulin A in Obesity and Metabolic Syndrome
Obese individuals were shown to have higher IgA levels in the blood than people with normal weight [R].
Immunoglobulin A Both Increased and Decreased in Diabetes
However, IgA levels were lower in elderly people with diabetes [R].
Also, milk from women with pregnancy-linked diabetes was 64% lower in IgA protein [R].
Immunoglobulin A Increases with Liver Damage
In patients with fatty liver, IgA levels were higher in those with more liver damage and inflammation (NASH) [R].
Low Immunoglobulin A Increases Cancer Risk
Those with IgA deficiency have a moderately increased risk of cancer, especially gut cancer [R].
Both Low and High Immunoglobulin A Increase the Risk of Mortality
Both low and high IgA levels are associated with higher mortality.
In 4,255 Vietnam-era war veterans, higher IgA levels were associated with a 2-fold increased risk of dying from both all-causes and infectious diseases [R].
In people aged 90 – 99 years, higher IgA levels were associated with higher mortality [R].
Similarly, in 8-year-olds, high IgA levels (>400 mg/dl) were associated with higher mortality. IgA levels were related to cancer mortality in males [R].
Severe IgA deficiency was associated with higher mortality in the first 10 – 15 years after diagnosis [R].
Immunoglobulin A Vasculitis and Nephropathy
IgA vasculitis occurs when IgA accumulates in the blood vessels and IgA nephropathy occurs when IgA accumulates abnormally in the kidneys.
In IgA vasculitis, IgA deposits in small blood vessels where it causes inflammation. Common symptoms are skin rash, joint pain, and swelling.
IgA vasculitis is more common among children, where the disease usually resolves within several weeks and requires no treatment. In adults, it can be more complicated and longer-lasting, with more severe kidney disease [R].
In IgA nephropathy, IgA complexes are deposited in kidneys. About 20 to 50% of patients develop progressive kidney failure [R].
Factors That Decrease IgA Levels
1) Chronic Stress
Acute stress (lasting a few minutes to a few hours) tends to stimulate the immune response [R].
Examination stress increased IgA levels in 15 nursing students. IgA decreased again two hours after the examination [R].
Contrarily, chronic stress, over a period of several days, weeks or months, decreases the immune response [R].
Chronic stress was associated with lower IgA in middle-aged and elderly subjects [R].
Perceived stress was associated with lower IgA in dental students [R].
In toddlers attending center or family child care at home, children with a lower quality of child care had lower IgA levels [R].
Low IgA is thought to be an important underlying mechanism linking chronic stress with increased upper respiratory tract infections [R].
Managing stress can help reverse the decrease in IgA. A study in 32 women showed that viewing unpleasant pictures decreased IgA levels. However, a reinterpretation of the situation (cognitive reappraisal) reversed the decrease of IgA [R].
2) Prolonged Exercise
IgA levels change depending on the intensity and duration of exercise, as well as the type of physical activity. Prolonged exercise decreases, while short-term and moderate exercise increase, IgA levels [R, R, R, R, R].
Professional athletes have lower IgA levels and are more prone to upper respiratory tract infections [R].
In 155 ultra-marathoners IgA levels decreased after racing [R].
Another study found that IgA also decreased in 64 ultra-marathon racers and 43 participants of an open water swimming race [R].
In soccer players, IgA decreased following training but returned to pre-training levels after 18 hours of rest. Overnight rest was sufficient for IgA recovery following training, but not following two successive matches [R].
In 13 international soccer players, IgA levels progressively declined during a four-day training period [R].
In 26 elite swimmers with a seven-month training season, pretraining salivary IgA levels were 4.1% lower with each additional month of training. Post-training IgA levels were 8.5% lower for each additional 1 km swum in a training session and 7.0% lower for each additional month of training [R].
Adolescent volleyball players had lower IgA levels compared with sedentary volunteers [R].
3) REM Sleep Deprivation
In a study of 32 volunteers, IgA levels decreased during four nights of REM sleep deprivation, but not after total sleep deprivation. The IgA levels did not return to baseline even after three nights of sleep recovery [R].
Some drugs can block REM sleep and may decrease IgA levels. These include antidepressants and sympathomimetics (drugs that mimic the action of adrenalin and dopamine and activate the sympathetic nervous system) [R, R].
Salivary IgA increases during sleep. In mice with disrupted circadian rhythms, salivary IgA failed to increase during sleep. It was shown that the increase in IgA was dependent on the sympathetic nervous system (fight-or-flight) activation, which is associated with REM sleep [R, R].
A couple of studies indicated that smoking tobacco and cigarettes can decrease IgA levels.
Tobacco chewers and tobacco smokers had decreased IgA levels compared to nonsmokers. Further, smokers had significantly lower IgA levels than chewers [R].
5) Sexual Activity in Women
During ovulation, immunity decreases to prevent immune interference with possible conception. Also, it is possible that there is a trade-off between investing energy in immunity and investing in reproduction.
This may explain why sexually active women have lower IgA levels than abstinent women [R].
Women with a high frequency of sexual activity had a decrease in IgA during ovulation. On the other hand, women with low frequency or no sexual activity had an increase in IgA during ovulation [R].
6) Certain Medications
IgA deficiency occurred in 20 to 40% of patients treated with phenytoin and persisted during the use of the medication [R].
Thirty-three epileptic children and adolescents treated with phenytoin had lower levels of IgA compared to healthy controls. The decrease in blood IgA levels correlated with the length of the treatment [R].
Factors That Increase IgA Levels
Chewing gum containing L. reuteri significantly increased IgA in the saliva (DB-RCT) [R].
In a study (DB-RCT) of 66 pregnant women, high-dose multi-strain probiotics resulted in infants with higher IgA levels and improved gut function [R].
The probiotic VSL#3 increased IgA production in monkeys [R].
Gut bacteria are important for IgA production. Germ-free mice have greatly reduced IgA production in the gut. Even a single strain of bacteria can effectively promote the production of gut IgA in germ-free mice [R, R].
Prebiotics are food for good bacteria. They improve our gut microbiome.
In a study (DB-RCT) with 187 infants, those who were exclusively fed formula and given prebiotics had higher IgA levels than infants who received a placebo [R].
Yacon flour, which is 50 – 70% prebiotic fiber, taken for 18 weeks increased IgA in 59 preschool children [R].
A prebiotic taken during pregnancy increased IgA levels in maternal milk in mice [R].
Relaxation can improve immune function and increase IgA levels.
In 24 volunteers, 20 minutes of relaxation significantly increased IgA production. Additionally, those who had practiced relaxation once a day for three weeks had larger increases in IgA levels than those practicing for the first time [R].
Ten minutes of relaxation increased IgA in 79 Japanese female medical workers [R].
Thirty minutes of Reiki, an alternative medicine healing technique, caused relaxation and increased IgA levels in 23 subjects [R].
People who use humor as a coping skill have higher baseline IgA levels [R].
Similarly, a funny presentation increased IgA levels in 21 fifth-graders compared to 18 of their classmates who watched an educational presentation [R].
Stressful events decrease IgA levels. Among 40 subjects, those with a sense of humor were less likely to have IgA reduced by stress [R].
Listening to music enhanced baseline IgA levels in 87 undergraduate students [R].
Similarly, in a group of 66 college students, those exposed to background music for 30 minutes had increased IgA levels [R].
Another study also showed that college students listening to music had increased IgA [R].
Participating in music may have an even greater effect.
Out of 33 subjects, those who actively sang or played percussions had greater increases in IgA levels than people who only listened to music [R].
Another study showed that singing in the choir increases IgA [R].
6) Short/Moderate Exercise
IgA levels increase in response to short-term or moderate exercise. This can help reduce the risk of respiratory infections [R].
Regular, moderate exercise increased IgA at rest in 9 subjects compared to 10 sedentary controls [R].
In 45 elderly individuals, 60-minute resistance and 60-minute moderate endurance training once a week significantly increased IgA after 12 months [R].
7) Venting/Expressing Anger
Among 18 healthy men and women with anger and depressive symptoms, IgA was increased in those who expressed their anger [R].
A meta-analysis of 13 studies and 1,034 patients concluded that glutamine increased IgA and decreased infectious complications in gut cancer patients [R].
Glutamine increased nasal but not salivary IgA during high-intensity interval training in 13 runners [R].
In 15 obese subjects, a 14-day fast increased blood IgA levels [R].
Intermittently fasted mice have higher IgA levels and are more resistant to infections [R].
10) Bright Light
11) Sexual Activity in Moderation
Among 112 college students, those who had frequent sex had highest IgA levels. The relationship between sexual activity and IgA levels had a reverse ‘U’ shape, with both those having very frequent and infrequent sex having lower IgA levels [R].
Further studies will hopefully clarify this point.
Infants receive IgA via breast milk. Then IgA production in the gut is gradually stimulated by developing gut microbiota [R].
13) Vitamin A
Vitamin A is needed for the transport and release of secretory IgA across the mucosa [R].
Vitamin A deficient rats and mice have decreased levels of total IgA in the gut, but their blood IgA levels are normal [R].
Breast milk of women supplemented with vitamin A had higher levels of IgA [R].
Four weeks of chlorella supplementation increased IgA in 15 men [R].
Chlorella also increased resting IgA in 26 subjects in intensive training [R].
Finally, chlorella increased IgA concentrations in breast milk of 18 pregnant women [R].
Blood IgA levels tend to increase with alcohol consumption. In 460 people, the highest IgA levels were observed in heavy drinkers [R].
White wine increased blood IgA in 5 men [R].
However, while blood IgA increases, gut IgA may actually decrease with alcohol. In mice, alcohol increased total IgA but decreased gut IgA. Alcohol may diminish the release of IgA into the gut [R].
In 24 volunteers, IgA production increased in those who ate white button mushrooms [R].
White button mushrooms increased IgA in mice [R].
However, at its higher dosage, it also blocked IgA release [R].
19) Thermal Water Inhalation
Thermal water comes from hot springs. It rises from deep underground and absorbs beneficial minerals on the way to the surface.
In 100 children with respiratory infections, those who inhaled sulfurous thermal water had higher blood IgA and better infection outcomes [R].
In another study, 25 patients treated with thermal water had increased nasal IgA compared to 25 patients treated with distilled water [R].
Acupuncture prevented the decrease in the salivary IgA due to intensive exercise in 12 men [R].
Genes and IgA
The following genes have been associated with IgA levels and IgA deficiency:
TNFSF8 is a cytokine that induces immune cell (T-cell) production.
This variant has also been associated with IBD [R].
IFIH functions as a sensor for viral infections [R].
This variant has also been associated with type 1 diabetes and lupus [R].
CLEC16A is a protein of unknown function found on white blood cells.
This gene of unknown function has been associated with cancer [R].
This variant could affect either ATG13, AMBRA1, or both genes (still unknown).
HS1.2 is an enhancer region important for immunoglobulin production [R].
HS1.21 increases the risk, while HS1.22 and HS1.2*4 decrease the risk of IgA deficiency (88 IgA deficient patients and 101 controls) [R].
HLA-DQA1 plays an important role in the immune system. It helps distinguish viruses and bacteria from the body’s own proteins.
Irregular IgA Levels?
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