What is Selective IgA Deficiency?
Immunoglobulin A (IgA) deficiency is the most widespread disorder that affects our immune system. It causes a decrease in a certain protein (IgA) in our blood, which is supposed to help fight off infections. Despite the drop in IgA, other protective proteins like IgG and IgM remain normal. This condition is generally diagnosed using an international consensus where individuals over the age of four having IgA levels below 7 mg/dl are classified as having IgA deficiency, provided that their IgG and IgM levels are normal. People with this deficiency usually have a normal response to vaccines. However, before confirming this deficiency, it’s essential to rule out other reasons that might cause a decreased protein level and issues associated with T cells (a type of white blood cell that plays a crucial role in our immune system).
Despite suffering from IgA deficiency, some people may show no signs or symptoms. However, this does not impact normal CD4 and CD8 T cells (types of T cells), as well as B lymphocytes (another type of white blood cell) in our body. Some patients might develop autoantibodies against their own IgA, essentially having their immune system counter-act against themselves.
People with IgA deficiency may also suffer from other diseases related to the immune system. These could be due to infections or medications, but such cases are generally reversible. Recent studies have shown that nearly 20-30% of patients with this deficiency are prone to severe respiratory and gastrointestinal infections and can react adversely to certain blood products. If these patients need a blood transfusion, it’s important to give them blood that lacks IgA to avoid any possible reactions.
Diagnosing IgA deficiency can be challenging, as there might not be any direct signs or symptoms. Instead, doctors must rely on indirect findings and their professional judgment. The condition might be suspected based on other health issues the patient is experiencing.
What Causes Selective IgA Deficiency?
Immunoglobulin A (IgA) deficiency is a kind of immune system disorder. It’s similar to other immune system deficiencies, but there are many ways it can develop.
When a baby is born, the mother gives something called IgG immunoglobulins to the baby, which are a type of protein that fights infections. But the baby doesn’t get another type of these proteins called IgA. Instead, the baby gets IgA from breast milk, and the protein helps prevent stomach infections.
In adults, you can also find IgA in the fluids from our stomach and lungs, such as saliva and tears. The amount of IgA in our bloodstream, on the other hand, is pretty low.
Sometimes, people can have an IgA deficiency without any clear reason. Other times, it seems to run in families, but there’s no clear pattern. It can also happen after taking certain medicines, like cyclosporine, gold, penicillamine, and medicine for seizures. Usually, stopping these medicines can reverse the IgA deficiency.
Some viral infections like Hepatitis C, Epstein-Barr virus, and congenital Rubella can also cause IgA deficiency. These infections can have a more long-lasting effect, with IgA deficiency happening after the infection and lasting for a long time.
Regardless of what causes IgA deficiency, it affects the same target: B-cells, a type of white blood cell. The deficiency could affect the growth of these cells, their maturation (when cells become specialized), or the production of IgA. Throwing off any of these processes can lead to IgA deficiency.
Risk Factors and Frequency for Selective IgA Deficiency
Selective IgA deficiency is a condition that can vary in its prevalence around the world due to differences in ethnic background. It’s most commonly found in individuals of White descent. The rate of occurrence can range from 1 in 143 people to 1 in 965 people depending on the region, and both males and females can equally have this condition.
It’s worth noting that the real rate may actually be higher, as routine screening for immunodeficiencies isn’t always done and many patients show no symptoms. If a family member has already been diagnosed with this disorder, the likelihood of another family member being affected is increased. It’s estimated that the occurrence of Selective IgA deficiency is 38 times higher among immediate family members of patients compared to unrelated donors, with approximately a 20% chance for family members to inherit the disease.
Signs and Symptoms of Selective IgA Deficiency
Many people with IgA deficiency often don’t show any symptoms throughout their lives and are only diagnosed during routine medical tests. However, for some, the deficiency may present varying conditions. They might show repeated respiratory infections, allergies, autoimmune diseases, stomach disorders, cancer, and other serious complications. These infections are often caused by certain types of bacteria, like Streptococcus pneumoniae and Haemophilus influenzae. The symptoms can be more severe when IgA deficiency is coupled with deficiencies of other immune cells, like IgG2 and IgG3.
- Recurrent respiratory infections.
- Allergies
- Autoimmune diseases
- Stomach disorders
- Cancer
About 20 to 30% of people with IgA deficiency have also been found to have autoimmune diseases, presenting symptoms like allergic eye inflammation, eczema, runny nose, hives, food allergies, and asthma. There’s also a link between IgA deficiency and type 1 diabetes, along with conditions like SLE, celiac disease, and Graves disease. This link is believed to be due to common genetics. These genetic overlaps can also make it hard to correctly diagnose conditions like celiac disease. Approximately 2 to 2.5% of people with celiac disease also have IgA deficiency.
It’s also possible that some autoimmune diseases can mask the symptoms of IgA deficiency, which can make it difficult to diagnose. Conditions like Ataxia-telangiectasia can be problematic due to multiple immunoglobulin deficiencies (IgA, IgG, and IgE). Patients with Hyper-IgM syndrome will have a lower IgA count as part of a condition where only the IgM count is high. These patients tend to suffer from severe infections and have a high blood viscosity due to their high IgM count, which can be genetically inherited. When diagnosing autoimmune diseases, doctors should always consider the possibility of a hidden IgA deficiency.
Testing for Selective IgA Deficiency
The European Society for Immunodeficiencies (ESID) has a specific set of criteria to diagnose selective IgA deficiency, a condition where the body is unable to produce enough of a certain type of protein (IgA) that helps fight off infections.
To receive a diagnosis for this condition, a few factors have to be present. Firstly, the patient’s IgA protein level needs to be undetectable through a test called nephelometry, but the levels of two other proteins called IgG and IgM need to be normal. These levels should have been measured at least twice.
Patients are also more prone to infections, particularly those that affect the respiratory system. The patient should be older than four years of age because that’s when this nephelometry test can accurately measure the IgA protein.
It’s also important to check if the patient has autoimmune diseases or if a family member has the same condition. Doctors should rule out other causes that may lead to lower than normal protein levels in the body (known as hypogammaglobulinemia).
When the patient receives vaccines, they should have a normal immune response to these vaccines, in the form of IgG proteins. Importantly, doctors need to ensure that there is no T cell defect, which could also affect the immune system’s function.
Specialized tests may also be done to examine the patient’s ‘switched memory B cells’, which are one type of immune cell. Some patients may have fewer of these cells, and these are often the ones with more pneumonia, autoimmune diseases, and enlarged liver or spleen.
For patients over 45 years old, a chest X-ray should be done to check for a tumor in the thymus gland.
Patients with recurrent diarrhea may be recommended to have a biopsy of their small intestine, as this can check for changes in the villi, which are tiny hair-like structures that absorb nutrients in the gut. This biopsy can also check if there are too few IgA-producing cells, and too many IgM-producing cells, in the lining of the gut.
It’s also important to note a potential problem related to celiac disease. Patients with both celiac disease and IgA deficiency may have misleading test results when screening for celiac disease. That’s because the tests look for specific IgA proteins, which are not present in enough amounts in patients with IgA deficiency. So, these tests might give a false negative result. That’s why it’s crucial to check the total IgA protein levels during the screen, and to check the levels of IgG and IgM proteins as well. It’s also worth mentioning that there could be a falsely positive pregnancy test due to an unusual production of auto-antibodies.
Treatment Options for Selective IgA Deficiency
Selective IgA deficiency is a complex condition that affects people differently, so there’s no one-size-fits-all treatment. Each patient’s care needs to be personalized. Care typically includes regular check-ups, prevention measures, and treatments for infections with antibiotics.
In some cases, antibiotics might be given based on a doctor’s best judgment even before the exact cause of an infection is known. This is often aimed at common bacteria like Streptococcus pneumoniae and Haemophilus influenza. When necessary, there can also be treatments for allergic conditions and autoimmune diseases, which are conditions where the body mistakenly attacks itself.
Sometimes, a patient might need replacement therapy where they’re given immunoglobulins, which are a type of protein the body normally makes to help fight off infections, through an IV or under the skin. This is rare, and doctors have to be careful to avoid a severe allergic reaction called anaphylaxis. If a patient has food allergies or issues with absorbing food, they might also have to adjust their diet.
Even if they don’t have any symptoms, all patients with IgA deficiency should get vaccines for pneumococcus bacteria and the flu. But they need to avoid vaccines that contain live viruses or bacteria because they could lead to severe infection. This includes vaccines for polio taken by mouth, a tuberculosis vaccine called Bacillus Calmette-Guérin (BCG), and the yellow fever vaccine.
What else can Selective IgA Deficiency be?
Diagnosing selective IgA deficiency can be tricky because it is often identified by ruling out other conditions. Here are some of the health problems that doctors need to exclude before they can diagnose IgA deficiency:
- Common variable immunodeficiency (CVID): This condition causes significant reductions in both IgG and IgA, and sometimes a reduction in IgM. CVID can lead to lower numbers of memory B-cells and defective responses to vaccines.
- Single gene primary immunodeficiencies: Conditions like X-linked hyper IgM syndrome show low levels of IgA, but can be differentiated from selective IgA deficiency.
- Thymoma: This condition is linked with moderate hypogammaglobulinemia and low or no circulating B cells. The immune system defect doesn’t usually mend after removing the thymoma.
- Chronic lymphocytic leukemia and lymphoma: These can decrease the level of IgA in the more advanced stages of the diseases.
- Multiple myeloma: This can cause an state of immunoparethesis, where levels of uninvolved immunoglobulins decrease due to increasing T and B-cell dysregulation.
- Drugs: Certain anti-rheumatic, antiepileptic drugs, and ACE inhibitors can lower the IgA levels.
IgA deficiency can often be overlooked because it does not have direct signs or symptoms. So the ability to identify the possibility of the deficiency, supplemented by professional suspicion, may be the best tools for diagnosis.
What to expect with Selective IgA Deficiency
In general, the outlook for patients with IgA deficiency is usually positive. Some people may naturally overcome the deficiency without any intervention. However, others might experience repeated instances of infection or inflammation, which could potentially be complicated by cancer or autoimmune diseases. Such conditions could lead to varying degrees of health deterioration, and this might give rise to concern.
Possible Complications When Diagnosed with Selective IgA Deficiency
The main complications associated with IgA deficiency are typically related to respiratory infections and cancers. Here are some of them:
- Obliterative bronchiolitis: This is a condition where the smallest airways in the lung become blocked due to inflammation. The damage to the lungs is more noticeable than in bronchiectasis. On x-rays, this can appear as “popcorn lung.”
- Bronchiectasis: Persistent lower respiratory infections in IgA deficient patients can result in long-term lung damage, leading to bronchiectasis. This is a permanent widening of bronchial airways caused by inflammatory damage. It’s mainly a result of recurrent infections, especially with bacteria like Haemophilus influenzae and Streptococcus pneumoniae.
- Pneumonia: Some doctors recommend daily preventative medication for patients with regular sinopulmonary infections.
- Increased risk of malignancies: There’s a higher chance of developing stomach cancers and lymphomas, particularly in older patients with IgA deficiency. Also, there’s a higher incidence of stomach adenocarcinomas amongst these patients. It’s suspected that this could be due to decreased levels of IgA antibodies that act against Helicobacter pylori, a bacterium known to cause gastrointestinal cancers.
- Gastrointestinal infections: IgA deficiency can increase the risk of developing giardiasis, an infection caused by a parasite called Giardia lamblia. Manifestations include chronic diarrhea, impaired nutrient absorption, and increased nodular lymphoid structures in the gut. While the standard treatment is an antibiotic called metronidazole, some patients may not respond to this medication.
- Transfusion reactions: Some sources suggest a relatively high prevalence (20-40%) of anti-IgA antibodies in patients with IgA deficiency. This increases the risk of reactions during blood transfusions, with approximately 20,000 to 47,000 cases of anaphylaxis reported per transfusion. Therefore, it’s recommended to give these patients washed red blood cells or blood products from a donor also deficient in IgA. These patients are also advised to wear a medical alert bracelet indicating their IgA deficiency.
- Severe COVID-19 infection: The absence of IgA, which normally lines the digestive system, might allow the coronavirus (COVID-19) to bypass mucosal barriers leading to a severe storm of inflammation that damages various organs and can lead to Acute Respiratory Distress Syndrome (ARDS). The lack of anti-SARS-CoV-2 IgA could be a cause of severe COVID-19 infections in these patients. It may also explain why vaccinations might not be as effective and why they may shed the virus for a longer period.
Preventing Selective IgA Deficiency
People diagnosed with selective IgA deficiency – a disorder that leads to a lower than normal level of IgA (a type of antibody that fights against infections in the body) – should take special care. They are recommended to use a medical alert bracelet for easy identification. Also, they should be aware of the risk of severe allergic reactions (known as anaphylactic reactions) after getting blood transfusions.
The blood products that are best for them come from other donors with IgA deficiency or are red blood cells cleaned with a saline solution. But even while using these special blood products, they must be used very carefully. Doctors and other medical professionals providing them should always be ready for the possibility of anaphylaxis, which is a severe and potentially life-threatening allergic reaction.
Also, it’s advised that all patients, whether showing symptoms of IgA deficiency or not, be checked regularly for signs of anti-IgA antibodies, which can indicate the presence of this disorder.
