Immunodeficiency Awareness Month: What Is The Science Behind These Diseases? Know Warning Signs

There are different types of primary immunodeficiency diseases, each caused by a different genetic defect that impairs the immune system function. Mutations are the primary reason.

Immunodeficiency Awareness Month: April is observed annually as Immunodeficiency Awareness Month, with the aim to educate the world about immunodeficiency diseases. When the body's immune response is reduced or absent, or when special white blood cells called T or B lymphocytes, or both, do not function normally, or the body does not produce enough antibodies, a person suffers from immunodeficiency disease. 

Immunodeficiency diseases are characterised by a compromised immune system that makes people more vulnerable to infections and other diseases.

Primary immunodeficiency diseases are rare, genetic disorders that impair and weaken the immune system, and allow infections and other health problems to occur more easily. Experts estimate that more than one million Indians are likely to have primary immunodeficiency diseases. 

The kind of problem and the underlying cause of an immunodeficiency disease determines the therapy for the disorder. Treatments for immunodeficiency diseases include bone marrow transplant, immunoglobulin replacement therapy, antibiotic therapy, vaccines and stem cell transplant, experts say.

The Science Behind Immunodeficiency Diseases

There are different types of primary immunodeficiency diseases, each caused by a different genetic defect that impairs the immune system function. 

Primary immunodeficiency diseases, also known as inborn errors of immunity, increase one's susceptibility to infectious diseases, autoimmunity, autoinflammatory diseases, allergy and malignancy, experts say.

Mutations are the primary reason behind immunodeficiency diseases.

“Mostly genetic due to errors in the DNA code, the blueprint of our body, leads to primary immunodeficiency diseases. These errors are commonly known as mutations, and lead to defective immune response and regulation. The diagnosis of primary immunodeficiency diseases is often delayed, or even missed altogether, especially in areas where infectious diseases are common as is the case in most developing countries,” Dr Sunit Chandra Singhi, Head, Department of Paediatrics, Amrita Hospital, Faridabad, told ABP Live.

Examples of primary immunodeficiency diseases include Bruton agammaglobulinemia, common variable immunodeficiency, and severe combined immunodeficiency.

“Bruton agammaglobulinemia is a rare disorder caused by a mutation in the BTK gene that primarily affects men. This gene codes for a protein that is required for the formation of B cells, which are responsible for creating antibodies to fight infections,” Varun Sheth, Co-Founder and CEO of Ketto India, told ABP Live.

In other words, Bruton type Agammaglobulinemia, also known as X-linked Agammaglobulinemia, Congenital Agammaglobulinemia, or X-linked Infantile Agammaglobulinemia is an inherited immune disorder caused by an inability to produce B lymphocytes or the immunoglobulins or antibodies that B cells make. This disease is caused by a genetic mutation, and reduces the ability of the immune system to fight infections. It is characterised by infections of the inner ear, respiratory tract, sinuses, internal organs and bloodstream.
“Common variable immunodeficiency is a group of disorders that impact B cell antibody production. Immunoglobulins, which are proteins that help fight infections, are low in people with this illness,” Seth said.

In other words, common variable immunodeficiency is a primary immunodeficiency disease characterised by low levels of protective antibodies, which renders the immune system unable to defend the body against bacteria and viruses, and results in recurrent and severe infections primarily affecting the sinuses, respiratory tract and ears, together called sinopulmonary infections. The antibody deficiency usually occurs in adults, but can also take place in children, and is also known as hypogammaglobulinemia.

“Severe combined immunodeficiency is a primary immunodeficiency disease in which both B cells and T cells are impacted. Due to their exceedingly low immune cell counts, people with severe combined immunodeficiency are incredibly vulnerable to infections,” Seth said.

In other words, severe combined immunodeficiency, also known as Swiss-type agammaglobulinemia is a group of rare disorders caused by mutations in different genes involved in the development and function of infection-fighting immune cells, and is characterised by the combined absence of T and B lymphocyte function, leading to extreme susceptibility to very serious infections, and symptoms such as pneumonia, blood infection, repeated ear infections, chronic skin infections, diarrhoea, test infections in the mouth, and liver infection. 

“To summarise, primary immunodeficiency illnesses are caused by genetic abnormalities that disrupt immune system development and function, making people more susceptible to infections. These illnesses are typically treated by strengthening the immune system with medicines or stem cell transplants,” Seth said.

However, not all immunodeficiency disorders have a cure, and are controlled through symptom management. 

How will one know if they are suffering from an immunodeficiency disease? What are its indicative factors?

The indicative factors which will help one know if they are suffering from an immunodeficiency disease are a family history of primary immunodeficiency disease and a failure to gain appropriate weight and height, among others.

Another important indicative factor is SPUR, which stands for Severe, Persistent, Unusual or Recurrent Infections. 

According to Dr Sanghi, immunodeficient patients with severe infections may require intravenous antibiotics, intravenous immunoglobulin replacement therapy, or hospital admission. 

People with persistent infections may not respond to standard treatment, and this could be an indicative factor for immunodeficiency disease. 

Patients with primary immunodeficiency diseases may suffer from unusual infections due to opportunistic pathogens. These infections do not occur in healthy children. 

If a person is suffering from recurrent or repeated infection at the same site or due to the same organism, they may have a primary immunodeficiency disease.

According to the Jeffrey Modell Foundation, an international organisation dedicated to helping individuals with primary immunodeficiency diseases, there is a set of 10 warning signs for suspecting primary immunodeficiency disease, Dr Sanghi said. The presence of two or more criteria is highly suggestive of primary immunodeficiency disease. 

The following are the 10 warning signs:

1) Four or more new ear infections within one year.
2) Two or more serious sinus infections within one year.
3) Two or more months on antibiotics with little effect.
4) Two or more pneumonias within one year.
5) Failure of an infant to gain weight or grow normally.
6) Recurrent, deep skin or organ abscesses.
7) Persistent thrush in mouth or fungal infection on skin.
8) Need for intravenous antibiotics to clear infections.
9) Two or more deep-seated infections including septicemia.
10) A family history of primary immunodeficiency.

Septicemia, or sepsis, refers to blood poisoning by bacteria, and is the body's most extreme response to an infection, according to Johns Hopkins Medicine. Infections most often associated with septicemia are lung infections, skin infections, urinary tract infections and infections in the intestines. 

People with immune system disorders such as immunodeficiency diseases, and weak immune systems are at risk for sepsis.

According to Seth, some indicators suggesting that a person is suffering from primary immunodeficiency are frequent or severe infections, taking longer than usual to recover from infections, a family history of immunodeficiency diseases, and reduced growth or development in children. 

Infants and children with immunodeficiency disorders may not grow or develop as expected. Also, people with a family history of primary immunodeficiency disease are at an elevated risk of developing the disorders because these illnesses are hereditary. 

Therefore, if one notices any of the warning signs and indicative factors in themselves or their family members, they must seek medical advice.