Immunoglobulin A is the first line of defense against harmful microbes, but it also maintains your immune tolerance. It is the dominant antibody in your gut, respiratory mucus, breast milk, and other secreted fluids. Read on to find out what the IgA blood test can tell you about your health and whether your levels are normal.
What is IgA?
Definition
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 [1].
IgA is one of the five immunoglobulin classes (in addition to IgG, IgM, IgD, and IgE) [1].
In the human body, more IgA is produced per day than all other antibodies combined [2, 3, 1].
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 [1, 2]:
- Gut mucus (intestinal barrier)
- Saliva
- Tears
- Breastmilk
- Respiratory mucus
- Urogenital mucus
IgA is also the second most prevalent antibody in the blood (after IgG) [2, 4].
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) [5].
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) [2].
IgA has many important functions:
- It is the first line of defense against harmful microbes [1, 3].
- It removes microbes that have breached the epithelial barrier (such as the intestinal barrier) [6].
- It can neutralize toxins and viruses [1, 7, 2].
- It shapes the composition of the gut microbiota [3, 1].
- It neutralizes inflammatory products from microbes [8, 9].
- IgA from mother’s milk helps program the infant immune system by regulating their microbiota and protecting them from pathogens [10].
- It helps maintain immune tolerance at mucosal barriers by dampening immune responses against good bacteria and food components [8].
Normal IgA Levels by Age
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 [11].
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
IgA Levels & Lifespan
Associations with 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 [12].
In people aged 90 – 99 years, higher IgA levels were associated with higher mortality [13].
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 [14].
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 [15].
Severe IgA deficiency was associated with higher mortality in the first 10 – 15 years after diagnosis [16].
High and low IgA levels can have many underlying causes. Thus, the health conditions triggering abnormal IgA levels are more likely to impact a person’s risk of dying than IgA levels themselves. Additional studies should give us more clues about this link.
IgA Genetics
If you’re not a big fan of genetics, skip straight to our other posts about IgA in the next section.
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 [17].
TNFSF8 is a cytokine that induces immune cell (T-cell) production.
This variant has also been associated with IBD [18].
IFIH1
IFIH functions as a sensor for viral infections [19].
Variant rs1990760 is associated with IgA deficiency (430 cases and 1,090 controls) [19].
This variant has also been associated with type 1 diabetes and lupus [19].
Another rs35667974 variant in the same gene was also associated with IgA deficiency (1,635 patients and 4,852 controls) [20].
CLEC16A
CLEC16A is a protein of unknown function found on white blood cells.
The rs6498142 variant in this gene is associated with IgA deficiency [19].
The rs34069391 variant is protective against IgA deficiency (1,635 patients with IgA deficiency and 4,852 controls) [21].
This gene has also been associated with type 1 diabetes, lupus, celiac disease, and multiple sclerosis [22, 23, 24, 25].
PVT1
The rs11299600 variant is protective against IgA deficiency [21].
This gene of unknown function has been associated with cancer [20].
ATG13 and AMBRA1
The rs4565870 variant was associated with IgA deficiency [21].
This variant could affect either ATG13, AMBRA1, or both genes (still unknown).
Both ATG13 and AMBRA1 are involved in the recycling of cell components (autophagy) [26, 27].
AHI1
The rs7773987 variant was associated with IgA deficiency [21].
This gene plays an important role in brain development. It has been associated with schizophrenia, autism, depression, and multiple sclerosis [28, 29, 30, 31].
HS1.2
HS1.2 is an enhancer region important for immunoglobulin production [32].
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) [33].
HS1.2 has been associated with psoriasis and rheumatoid arthritis [34, 35].
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) [21].
This gene has been associated with celiac and Graves’ disease [36, 37].
Takeaway
Immunoglobulin A (IgA) is an antibody made by white blood cells. It’s concentrated in fluids that cover mucous membranes in the body–such as those in the gut, respiratory system, eyes, and mouth. IgA works to protect the body from infections and toxins while building immune tolerance. Normal IgA levels prevent the immune system from mounting an attack against food components and good bacteria in the gut. Your doctor may order a blood test to check if your IgA levels are normal. The normal range depends on age; it is lower and more narrow in babies and children. In adults, values between 60 and 400 mg/dL are considered normal by most labs. Make sure to discuss your results with your physician.
Learn More
- Low IgA & Selective IgA Deficiency: Causes & Symptoms
- Causes of High IgA Levels
- Low IgA Levels? 21 Ways to Improve Immune Health
- High IgA Levels? 5 Ways to Improve Immune Health
