Immunodeficiency: Definition and examples

Immunodeficiency, immunocompromised and autoimmune disorder are all terms that describe the body's immune system and its reduced ability or inability to fight off infection or disease. But the terms aren't always interchangeable. Here's what each one means. 

What are immunodeficiency disorders?

Immunodeficiency disorders are immune system malfunctions that may prevent a person's body from defending itself against disease or infection.

It could mean the body's immune system doesn't produce enough immune cells or antibodies to fight off foreign invaders or that the body's immune response is absent.

As with many medical conditions, immunodeficiency can range from mild to severe. In mild instances, someone who is immunodeficient may not even realize it, according to M. Elizabeth M. Younger, an assistant professor of pediatrics at the Johns Hopkins School of Medicine in Maryland. That's because you can be asymptomatic with some of the milder forms.

There are two types of immunodeficiency disorders, according to the British Society of Immunology: primary and secondary. Primary immunodeficiency disorders are those that are genetic or hereditary, while secondary immunodeficiency disorders develop as a result of environmental factors and are more common than primary immunodeficiencies. 

Primary immunodeficiency

There are more than 400 types of primary immunodeficiencies, according to the Centers for Disease Control and Prevention (CDC). Symptoms of the more serious primary disorders, such as severe combined immunodeficiency (SCID) tend to present in infancy, according to the American Academy of Allergy, Asthma & Immunology, whereas symptoms of the less serious disorders may not show up until adulthood. For example, the median age of onset for common variable immunodeficiency (CVID) is 24 years, according to a 2014 review published in Allergo Journal International.

Signs of a primary immunodeficiency disorder include the following:

• Frequent or recurring infections, which can include sinus infections, ear infections, bronchitis, pneumonia, skin infections or candidiasis (a fungal infection caused by a type of yeast called Candida)
• Lingering infections
• Bacterial infections that don't respond well to antibiotics
• Infections that require hospitalization, such as sepsis

Treatments vary depending on the type of immunodeficiency disorder and the particular infection. 

The most common primary immunodeficiency disorder is selective IgA deficiency (SIgAD), according to the Immune Deficiency Foundation. People with selective IgA deficiency lack immunoglobulin A, or IgA, which is an antibody found in the mucous membranes of the respiratory and digestive tracts, according to Johns Hopkins Medicine. 

SIgAD is occurs most often in people of European descent, according to the Cleveland Clinic. For some, SIgAD can cause significant illness, but that's not the case for many people with this disorder, Younger said. Some people don't even notice any symptoms. 

The vast majority of them have no clue that their IgA levels are very low or missing altogether. "They walk around, completely asymptomatic, and it's never problematic at all," Younger said. 

However, the deficiency does increase a person's vulnerability to infections, as do other primary immunodeficiency disorders. 

Secondary immunodeficiency

Secondary immunodeficiency disorders are more common than primary immunodeficiency disorders, according to a 2009 review published in the Journal of Allergy and Clinical Immunology, and develop as a result of environmental factors. For example, secondary immunodeficiency disorders can be caused by HIV infection; certain drugs, such as drugs to prevent rejection of transplanted organs; or treatment with chemotherapy. Malnutrition is the most common cause of immunodeficiency around the globe, as calorie deficiency and micronutrient deficiencies can alter the immune response. 

Symptoms of a secondary immunodeficiency disorder include frequent infections and occasional opportunistic infections, which tend to occur more frequently in people with weakened immune systems. For example candidiasis is a fungal infection caused by the Candida yeast. The yeast can live on your skin and in your body without causing any problems, but if you have a weakened immune system, it can grow out of control and cause infections, according to the CDC.

Diagnosis & treatment

To diagnose an immunodeficiency, a doctor will likely conduct a physical examination, get a thorough patient history and perform a variety of tests, according to the Merck Manual. The tests may include blood tests, skin tests, lymph node or bone marrow biopsy, and sometimes genetic testing to identify a genetic mutation that could be causing the disorder. 

The type of treatment depends on the type of immunodeficiency disorder. According to National Jewish Health, treatment may include antimicrobial therapy for infections, vaccinations, or specialized therapies to replace or supplement immune system cells. 

The prognosis for people with immunodeficiency disorders varies, too. Many people with primary immunodeficiency need ongoing treatment with antibiotics and antifungals to ward off infection. In the case of some secondary immunodeficiencies, treatment of the primary cause can effectively resolve the immunodeficiency, according to the British Society for Immunology; an example is malnutrition. 

Is immunodeficiency the same as autoimmune disease?

Immunodeficiency disorders and autoimmune disease are not exactly the same. An immunodeficiency is an impairment of the immune system, whereas an autoimmune disease is when the immune system attacks the body's healthy cells, tissues and organs. 

However, studies have found that there often is a connection between immunodeficiencies and autoimmune diseases. "Patients with certain kinds of immunodeficiency have a propensity to autoimmune disease," Younger said, adding that it's common for an autoimmune disease to develop after the diagnosis of an immunodeficiency. "They absolutely go hand in hand," she said. 

People with a primary immunodeficiency are more likely to have an autoimmune disorder, certain blood disorders and cancers, according to the CDC, because their immune systems just don't work as effectively to protect them from these health problems.

There are more than 80 recognized autoimmune diseases, including type 1 diabetes, inflammatory bowel disease and rheumatoid arthritis, according to the National Institute of Allergy and Infectious Diseases. Medicines prescribed to treat autoimmune disorders typically work to suppress the immune system in order to slow it down or prevent it from attacking the body and, in doing so, increase the risk of other infections. So there is some overlap: a person can be immunodeficient or immunocompromised because of treatment they're receiving for an autoimmune condition. 

Is immunodeficiency the same as immunocompromised?

Immunocompromised is a broad term for describing someone with a weakened immune system. People who are immunocompromised have a higher risk of getting sick — as their immune system has a harder time fighting off bacteria, viruses and other invaders — than someone with a healthy immune system. 

People with immunodeficiency or autoimmune disease are considered immunocompromised, but other factors can also cause someone to be immunocompromised, such as cancer, cancer treatments, metabolic disorders or advanced age, according to The University of Texas MD Anderson Cancer Center. Transplant patients and smokers are also immunocompromised, according to Penn Medicine. 

Immunodeficiency and COVID-19

Anyone with an immunodeficiency may be at increased risk for developing serious complications if they contract COVID-19, according to the CDC. People with cancer; chronic conditions, such as chronic liver or lung disease; or autoimmune conditions may also be at increased risk. Research supports this, as a study published in late 2020 in the Journal of Allergy and Clinical Immunology found that adults with primary immunodeficiencies and symptomatic secondary immunodeficiencies experienced greater morbidity and mortality from COVID-19. 

Anyone who is immunocompromised should get vaccinated against COVID-19, said Dr. Aaron E. Glatt, chairman of the Department of Medicine and chief of infectious diseases at Mount Sinai South Nassau and a spokesperson for the Infectious Diseases Society of America. But the vaccine is not a perfect solution. "We are understanding that people who are immunocompromised are not as responsive to the vaccine, which is a major concern," Glatt said. 

Research from the University of Pittsburgh School of Medicine found that some groups of immunocompromised patients are unable to produce enough antibodies to protect them from COVID-19, and therefore still have an increased risk of infection even after vaccination. This study has not been peer reviewed and is available on the preprint server MedRxiv. 

People whose immune systems are impaired should be extra cautious about protective measures, including social distancing and mask wearing, Glatt said.

Additional resources

• Learn more about primary immunodeficiency in children in this article and video from the Children's Hospital of Philadelphia. 
• Read about one person's discovery of his undiagnosed immunological disorder in "A Family History of Illness: Memory as Medicine," (University of Washington Press, 2018) by Brett L. Walker. 
• Learn out more about immunodeficiency research and find helpful resources from the Immune Deficiency Foundation. 

This article is for informational purposes only and is not meant to offer medical advice.