Top Causes of
Immunodeficiency Disorders

Primary Immunodeficiency

Primary immunodeficiency disorders (PIDs) are inherited immunodeficiencies that are sometimes caused by single-cell mutations but more often caused by a combination of environmental factors and unknown genetic susceptibilities. Though some doctors will catch PIDs early in a child’s life, most people remain undiagnosed until long into adulthood. PIDs are further classified based on the part of the immune system the disrupt.

Causes of PIDs

When it comes to both primary and secondary immunodeficiencies, the causes and conditions are one and the same. For this reason, when discussing “causes,” we will actually be discussing specific disorders. Below are the top causes of primary immunodeficiency disorders.

B cell immunodeficiencies

B cells are one of two main types of cells that make up the adaptive immune system and, as such, carry out critical functions. The main job of B cells is to produce antibodies, which are proteins that attach to microbes so that the other immune cells more easily spot and destroy them. When B cells malfunction due to mutations within them, antibody production decreases. As a result, persons who experience B cell immunodeficiencies often experience recurrent infections.

T cell immunodeficiencies

T cells is the second of the two main types of cells that make up the adaptive immune system. T cells carry out several important functions, one of the most important of which is to activate B cells and pass along details of the microbe’s identity so that B cells may produce the correct antibodies. T cells also help to kill microbes and signal the activation of other cells within the immune system.

When T cells develop or exist with mutations, there may be fewer of them or, if not fewer, they function improperly. The lack of properly functioning T cells can interfere with their ability to kill microbes, thereby leading to an increased susceptibility to illness and possible problems with B cell function. If the latter happens, a person may develop combined immunodeficiencies (CIDs) in which both T and B cell function is defective. As you may imagine, CIDs are more severe than PIDs, with some being more serious than others.

Severe combined immune deficiencies (SCID)

CIDs are immunodeficiency disorders in which both B and T cells have mutations and/or function improperly. With SCIDs, the same is true, except the condition is, as its name implies, severe.

With SCID, a person often lacks T cells completely and has a low but varying number of B cells. As a result, he or she has little-to-no immune function, meaning even the most minor infections can be deadly. Though rare, SCID disorders are extremely dangerous. Fortunately, most patients are typically diagnosed within the first year of life after multiple recurrent infections and failure to thrive. Early diagnosis is key to managing the condition and ensuring future long-term health.

Complement defects

Among all PIDs, complement defects are some of the rarest, accounting for less than 1% of all diagnosed cases. Complement defects affect the complement proteins within the blood, the job of which is to help immune cells clear infection from the body. When complement deficiencies are present, patients are often prone to autoimmune disorders such as rheumatoid arthritis and systematic lupus erythematosus. Many are also highly susceptible to meningitis.

Phagocyte disorders

Phagocytes consist of many of the white blood cells that make up the innate immune system. Their job is to patrol the body and eat any pathogens they find along the way. When these monitors experience mutations, they may become unable to effectively destroy pathogens. While individuals with disorders of the phagocyte typically have highly functioning immune systems when faced with most pathogens, certain fungal and bacterial infections can cause considerable harm and possibly even death.

Secondary Immunodeficiency

Secondary immunodeficiency disorders, or SIDs, are much more common than PIDs and are caused by external factors, such as malnutrition, drug use or infections. Most SIDs can be resolved simply by treating the primary infection, though this is not the case with all of them, such as HIV. Some of the most common causes of SIDs are as follows:

Medication regimens

There are dozens of prescription medications that, though they serve a beneficial purpose, also suppress the immune system. For example, corticosteroids, which are used to treat allergic reactions, lupus, asthma, eczema, inflammation and a host of other conditions, suppress the immune system for the duration of a course of treatment. So, too, do most types of chemotherapies. Immunosuppressants are also used to prevent transplant rejection, as, if the immune system is fully aware and activated, it may target the transplanted tissue as an invader and attack it.

Though the immune system typically recovers once immunosuppression therapy has ended, the body is susceptible to a range of illnesses and infections in the meantime. For this reason, researchers are working on a new generation of medicines called biologics, which come from biological resources, such as cells. Because of their biological components, they are less likely to interfere with immune system function.

Malnutrition

Protein-calories malnutrition is the leading cause of SIDs on a global scale, affecting up to as much as 50% of the population in some parts of the world. When malnutrition occurs, T cell function and production decrease in proportion to the level of protein deficiency. Both lack of protein and improperly functioning T cells can cause respiratory tract infections and diarrhoea, which can further exacerbate the condition. That said, with healthy changes to the diet, proteins-calories malnutrition can easily be resolved.

Chronic infections

There are several chronic infections that can trigger secondary immunodeficiency disorders, the most common and commonly known of which is acquired immune deficiency syndrome, or AIDS. When a person has AIDS, the virus attacks the CD4+ T cells, which is a type of white blood cells that’s very job is to prevent infection. As the virus continues to attack those cells, their numbers quickly deplete. Once T cell counts drop to less than 200 cells per ml of blood, AIDS symptoms grow progressively worse, resulting in recurrent infections that eventually lead to death.

Though the outlook is grim for AIDS patients, the good news is that researchers are continually working on anti-viral therapies that give T cell populations a chance to recover and resume normal function. Thanks to such therapies, HIV/AIDS patients enjoy both a higher quality of life and a higher life expectancy than in former decades. Prior to the introduction of such treatments, HIV patients who were diagnosed at the age of 20 had an average 10-year period in which they could live a somewhat normal life before developing AIDS. Today, however, a 20-year-old who is diagnosed with HIV can expect to live well into their 60s before developing the more serious AIDS virus. However, as these drugs are not curative, they must be taken every day of one’s life. Moreover, because they are cost-prohibitive, they are typically only available to people with health insurance and in countries that can afford them.