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?

Immunoglobulin A (IgA) is a type of antibody. Antibodies are proteins of the immune system that bind to and neutralize pathogens such as bacteria and viruses [R].

IgA is one of the five immunoglobulin classes (in addition to IgG, IgM, IgD, and IgE) [R].

In the human body, more IgA is produced per day than all other antibodies combined [R, R, R].

IgA is produced by white blood cells (B cells) and is then transported into fluids secreted by mucosal cells. This IgA is called the secretory IgA. Secretory IgA is the dominant antibody in [R, R]:

  • Gut mucus (intestinal barrier)
  • Saliva
  • Tears
  • Breastmilk
  • Respiratory mucus
  • Urogenital mucus

IgA is also the second most prevalent antibody in the blood (after IgG) [R, R].

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].

IgA Function

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

Lower IgA means your immunity is weakened. Also, it may indicate a disturbed intestinal barrier and/or gut microbiota [R, R, R].

Chronic stress, poor sleep, and exhaustion decrease IgA [R, R, R, R].

Medications such as phenytoin and chemotherapy can also lower IgA levels [R, R, R, R].

Having low IgA increases the risk of allergies, infections, and autoimmune diseases [R, R, R, R].

Low IgA can be found in individuals with:

IgA Deficiency

IgA deficiency is the most common primary immunodeficiency. Prevalence is higher in whites (1:155 in Spain, around 1:500 in general) and lower in Asians (1:18550 in Japan) [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].

Eighty-five to 90% people with IgA deficiency have no symptoms. Those with symptoms usually have respiratory or gut infections [R, R].

IgA-deficient people have a tendency to develop infections and disorders of the gut, such as malabsorption, lactose intolerance, celiac disease, and ulcerative colitis [R, R].

Other autoimmune diseases, such as hemolytic anemia, type 1 diabetes, rheumatoid arthritis, thyroid disorders, and lupus are also more frequent in IgA-deficient people [R, R].

IgA-deficient people more often have allergies, including asthma, allergic rhinitis/conjunctivitis, drug allergy, or food allergy [R].

They also have a higher prevalence of atopic dermatitis, acne, and chronic spontaneous hives [R].

There is no specific treatment for this condition. Antibiotics are prescribed in those with infections [R].

First-degree relatives of IgA-deficient patients also have increased risk of autoimmunity (10% compared to an estimate of 5% in the general population) [R].

High IgA

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]

IgA-Associated Diseases

Low IgA Increases 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].

Also, higher blood IgA levels were associated with lower risk of eczema at 18 months of age [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 IgA Increases 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].

Prolonged exercise decreases IgA. Suppressed IgA was associated with an increase of respiratory infections in ultramarathoners [R].

IgA 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].

Multiple studies report an increased prevalence of IgA deficiency in patients with celiac disease and increased prevalence of celiac disease in patients with IgA deficiency [R, 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].

IgA 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].

IgA May Be Decreased in IBD Patients

IBD is associated with IgA deficiency [R, R].

In ulcerative colitis in Crohn’s patients, IgA production in the gut was decreased [R, R].

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].

IgA 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].

IgA 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 a lower IgA levels in autistic people [R].

Increased IgA in Obesity and Metabolic Syndrome

Obese individuals were shown to have higher IgA levels in the blood than people with normal weight [R].

In the same study, blood IgA levels were also higher in those with metabolic syndrome. This includes people with elevated triglycerides, high blood sugar, or high blood pressure [R].

However, other studies found normal IgA levels in obese people, and even lowered levels in obese children [R, R, R].

IgA Both Increased and Decreased in Diabetes

One study found increased blood IgA levels among diabetic patients. Diabetic complications were also associated with higher IgA levels [R].

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].

IgA Increases with Liver Damage

In patients with fatty liver, IgA levels were higher in those with more liver damage and inflammation (NASH) [R].

Also, in hepatitis B-infected patients, IgA was significantly increased in those with liver injury [R].

Low IgA Increases Cancer Risk

Those with IgA deficiency have a moderately increased risk of cancer, especially gut cancer [R].

Both Low and High IgA 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].

On the other hand, higher IgA was associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease [R].

Severe IgA deficiency was associated with higher mortality in the first 10-15 years after diagnosis [R].

IgA 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 mothers, breast milk IgA was lower in those who experienced more anxiety, depression, anger, fatigue, and confusion [R].

In toddlers attending center or family child care at home, children with lower quality of child care had lower IgA levels [R].

Studies on rodents under stress have also reported a decrease in intestinal IgA [R, 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 sympathetic nervous system (fight-or-flight) activation, which is associated with REM sleep [R, R].

4) Smoking

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].

In mice, three months of cigarette smoke exposure before influenza virus infection resulted in reduced IgA levels and increased lung inflammation [R].

However, some studies showed no differences in IgA levels in smokers [R, 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 into immunity and investing into 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

Drugs used for the treatment of seizures, rheumatoid arthritis, and IBD have all been associated with IgA deficiency [R].

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].

Low IgA was also recorded with thioprine, cyclosporine A, fenclofenac, and anti-TNF-alpha drugs [R, R, R, R].

Finally, chemotherapy reduced IgA in cancer patients, especially those with leukemia [R, R, R].

7) Cocoa

In animal studies, cocoa decreased IgA in the blood, gut, and saliva [R, R].

Factors That Increase IgA Levels

1) Probiotics

In a study (DB-RCT) with 47 people, a three-week daily intake of the probiotic L. reuteri increased IgA levels [R].

In 30 athletes, IgA substantially decreased after training in the placebo group, but not in athletes who took L. helveticus (DB-RCT) [R].

Chewing gum containing L. reuteri significantly increased IgA in the saliva (DB-RCT) [R].

Probiotics increased IgA levels and improved recovery in 40 children with burn injuries [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].

Daily ingestion of L. casei increased IgA levels in 14 subjects [R].

In a study of 98 newborns, B. bifidum increased IgA levels in low birth weight infants [R].

In a study of 413 infants, those who took formula enriched with B. lactis had higher IgA levels that were similar to the levels seen in breastfed infants [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].

Probiotics increased IgA production in mice and rats, improved gut function, and protected against inflammation and infection [R, R, R, R, R, R].

2) Prebiotics

Prebiotics are food for good bacteria. They improve our gut microbiome.

A prebiotic mixture increased IgA levels and improved metabolic parameters (CRP, insulin, total cholesterol, and triglycerides) in 45 overweight adults (DB-RCT) [R].

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].

Prebiotics increase IgA in rats and mice [R, R, R].

A prebiotic taken during pregnancy increased IgA levels in maternal milk in mice [R].

3) Relaxation

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].

In 14 breast cancer patients, IgA was higher after surgery in those who participated in a relaxation method called autogenic training [R].

Thirty minutes of Reiki, an alternative medicine healing technique, caused relaxation and increased IgA levels in 23 subjects [R].

4) Humor

People who use humor as a coping skill have higher baseline IgA levels [R].

Watching a comedy increased IgA in 15 university students and 39 women [R, 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].

5) Music

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].

Several studies showed that moderate exercise increases IgA in elderly individuals [R, R, 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].

Domestic abuse perpetrators prone to express their anger have higher IgA levels [R, R].

8) Glutamine

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].

Glutamine supplementation increased IgA production in the gut of mice and rats [R, R].

9) Fasting

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

In a study of 7 women, exposure to bright light during the day increased IgA levels compared to when they were exposed to dim light [R].

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].

These results are conflicting with others that show decreased IgA with sexual activity in women [R, R].

Further studies will hopefully clarify this point.

12) Breastfeeding

Infants receive IgA via breast milk. Then IgA production in the gut is gradually stimulated by developing gut microbiota [R].

Several studies show that breastfed infants have higher IgA levels [R, R, 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].

14) Chlorella

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].

15) Alcohol

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].

16) Mushrooms

In 24 volunteers, IgA production increased in those who ate white button mushrooms [R].

White button mushrooms increased IgA in mice [R].

Compounds found in Reishi mushrooms increased IgA in mice [R].

17) Estrogen

In 86 women, those with higher estradiol (main estrogen) had higher IgA levels [R].

In cell studies, estrogens increase IgA transport into the mucus, which decreases bacterial invasion [R, R].

18) Ginseng

Ginseng enhanced gut IgA production in mice [R, R, 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].

20) Acupuncture

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

A study in 9,617 subjects showed that IgA levels were associated with the rs13300483 variant in the TNFSF8 gene [R].

TNFSF8 is a cytokine that induces immune cell (T-cell) production.

This variant has also been associated with IBD [R].

IFIH1

IFIH functions as a sensor for viral infections [R].

Variant rs1990760 is associated with IgA deficiency (430 cases and 1,090 controls) [R].

This variant has also been associated with type 1 diabetes and lupus [R].

Another rs35667974 variant in the same gene was also associated with IgA deficiency (1,635 patients and 4,852 controls) [R].

CLEC16A

CLEC16A is a protein of unknown function found on white blood cells.

The rs6498142 variant in this gene is associated with IgA deficiency [R].

The rs34069391 variant is protective against IgA deficiency (1,635 patients with IgA deficiency and 4,852 controls) [R].

This gene has also been associated with type 1 diabetes, lupus, celiac disease, and multiple sclerosis [R, R, R, R].

PVT1

The rs11299600 variant is protective against IgA deficiency [R].

This gene of unknown function has been associated with cancer [R].

ATG13 and AMBRA1

The rs4565870 variant was associated with IgA deficiency [R].

This variant could affect ether ATG13, AMBRA1 or both genes (still unknown).

Both ATG13 and AMBRA1 are involved in the recycling of cell components (autophagy) [R, R].

AHI1

The rs7773987 variant was associated with IgA deficiency [R].

This gene plays an important role in brain development. It has been associated with schizophrenia, autism, depression, and multiple sclerosis [R, R, R, R].

HS1.2

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].

HS1.2 has been associated with psoriasis and rheumatoid arthritis [R, R].

HLA-DQA1

HLA-DQA1 plays an important role in the immune system. It helps distinguish viruses and bacteria from the body’s own proteins.

The rs116041786 variant was associated with IgA deficiency (1,635 patients with IgA deficiency and 4,852 controls) [R].

This gene has been associated with celiac and Graves’ disease [R, R].

 

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  • Marcela Kern

    Thank you so much for this post, which makes me much more confident about discussing my health issues with my doctors, without the fear of appearing totally ignorant or of getting a wrong diagnosis. I know that this can’t be completely avoided, but having up to date information that is concise, complete, accurate and with all references is a great, great help! Again, Thank you!

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