What Are Primary Antibody Deficiency Disorders?

Disorders That Can Make You Prone to Certain Infections

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Primary antibody deficiency disorders are a group of related conditions that affect a person’s B cells and their ability to produce functioning antibodies. Because of this, people with these conditions are prone to getting certain types of infections, and they may have more trouble fighting them off. 

These diseases are sometimes called “primary humoral immunodeficiency diseases” or “B cell disorders.” You also might hear about a specific type of antibody deficiency disorder, such as Bruton disease. 

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Primary Immunodeficiency Disorders

Primary antibody deficiency disorders are part of a larger group of medical conditions called primary immunodeficiency disorders. These are a wide group of diseases that cause some part or parts of the immune system to not work properly. 

The word “primary” just refers to the fact that the problem is not the result of another health condition (like an immunosuppressant drug or an infectious disease like AIDS). These or other issues might cause low or ineffective antibodies, but they aren’t grouped with this type of “primary” antibody deficiency.

Different types of primary immunodeficiency diseases affect different parts of the immune system. Those that affect primarily B cells are called antibody deficiency disorders or “humoral” immunodeficiency diseases. Of people that have a primary immunodeficiency disease, about 50% have some sort of primary antibody deficiency disorder.

Primary immunodeficiency disorders that affect both B cells and have significant impact on another part of the immune system, like T cells, often cause more severe symptoms. These are not generally included with primary antibody deficiency disorders, even though they also affect a person’s antibodies.

An example of this that some people are familiar with is severe combined immunodeficiency (SCID), commonly known as "bubble boy" disease.

Types of Primary Antibody Deficiency Disorders

Antibody deficiency disorders are further separated into specific disorders, based on their underlying genetic causes and the exact types of antibodies affected. Some of the most common types include:

Another important type of antibody deficiency disorder is called transient hypogammaglobulinemia of the newborn. Unlike these others, this isn’t thought to primarily be a genetic disorder.

It is a temporary situation in which a young child has lower than normal levels of various antibodies during infancy, which can leave them prone to various infections. Levels of antibodies usually return to normal some time in childhood, but sometimes not until later in life.

Each of these disorders affects the body’s B cells and antibody production in slightly different ways. They all lead to slightly different risks of symptoms.

Antibody Deficiency Disease Symptoms

The symptoms of these disorders mostly result from different kinds of infections. A person might get these infections frequently and might not be able to get rid of them easily.

These people are more prone to getting specific types of bacterial infections, particularly “encapsulated” type bacteria such as Streptococcus pneumoniae. They may also be more likely to get some kinds of infections by viruses or parasites.

The exact symptoms will vary based on the specific type of infection. For example, someone might have chest pain, cough, and fever from pneumonia or from bronchitis. Other types of infections could cause symptoms from a sinus infection or an infection of the middle ear. 

Other possibilities include diarrhea from a gastrointestinal infection that might be temporary or long-term. Other times, a person might develop hot, red skin from a skin infection. Many other types of infections are possible as well.

People with antibody deficiencies may get infections repeatedly. Moreover, they might not respond as well as someone else to standard therapies, like oral antibiotics. And an infant with an antibody deficiency disease might not gain weight normally (known as “failure to thrive”), due to repeated infections.

Different kinds of primary humoral immunodeficiency diseases carry slightly different risks in terms of infection. For example, people with IgA deficiency are more prone to getting infections of the sinuses and the pulmonary system. 

Some people with milder versions of antibody deficiency diseases do not experience any symptoms. For example, the majority of people with IgA deficiency don’t have noticeable symptoms from an increased number of infections.

If a person does experience symptoms, these often are not present right at birth but take several months to show up. At birth, the infant has some antibody protection it has received from the mother. This protection may last a few months or so.


Sometimes people with these disorders develop complications from having repeated infections. For example, someone with repeated lung infections might develop irreversible lung damage, such as bronchiectasis (permanent damage to the bronchial tubes of the lung).

This is one of the reasons it’s important to diagnose these disorders promptly, before long-term damage has occurred. 

Risks of complications vary among different types of antibody deficiency disorders. For example, people with CVID have an increased risk of certain kinds of autoimmune diseases, such as alopecia, vitiligo, juvenile idiopathic arthritis, as well as low levels of red blood cells, white blood cells, or platelets.

Some kinds of antibody deficiency diseases also increase a person’s risk of some kinds of cancer. For example, people with CVID have an increased risk of gastric cancer and lymphoma.

Even if they don’t experience an increased number of infections, people with IgA deficiency may have an increased risk of allergies, autoimmune diseases, and certain types of cancer (like lymphoma).


Most of the time, these diseases are caused by a genetic problem that is present from birth. 

For example, X-linked agammaglobulinemia is caused by a mutation in a gene known as BTK. Because of the problem with this gene, the person can’t make an important protein needed to help B cells mature normally. This ultimately causes a deficiency in antibodies. 

There are five different types of antibodies that perform somewhat different functions, including types IgG, IgM, and IgA. These different disorders have varying effects on the production of different subtypes of antibodies. 

For example, IgA deficiency only affects antibodies of the IgA subtype. In hyper IgM syndrome, a person can make normal IgM antibodies, but these antibodies can’t switch over to make other subtypes of antibodies, the way they normally would. 

That’s part of the reason symptoms and severity vary among different types of antibody deficiency disorders. Deficiency in different specific types of antibodies leave one more vulnerable to specific types of infections.


Antibody deficiency diseases can be diagnosed any time during childhood or adulthood. It’s critical that healthcare professionals consider the possibility of an antibody deficiency disorder or another type of primary immunodeficiency disease in a person who has suffered from repeated infections.

It’s important that the antibody deficiency itself be diagnosed and not just the current infection that might have led a person to seek treatment. Such individuals need treatment to fight off these infections directly but also specially targeted therapies to help address their immune problems. 

Unfortunately, diagnosing antibody deficiency diseases is sometimes challenging. Because these diseases are rare, clinicians may not be thinking to check for them. Not everyone with these disorders shows the same kinds of symptoms, which can make diagnosis difficult.

Also, it is often challenging to diagnose these conditions with the laboratory tests that are readily available at some health centers.

A thorough medical history and medical exam are key parts of diagnosis. Family history can sometimes provide some clues, because these disorders can run in families. However, it’s important to note that even among people with the same disorder in the same family, severity can vary quite a bit.  

It’s especially important that the clinician ask about past instances of recurrent infection, which may point to an antibody deficiency as a cause. For example, the following are some possible red flags for a possible antibody deficiency disease in a child:

  • Four or more ear infections in a year
  • Two or more serious sinuses infections a year
  • Two more pneumonias a year
  • Recurrent skin abscesses
  • Persistent fungal infections
  • Poor response to oral antibiotics

Laboratory Work-up

If an antibody deficiency disorder is suspected, the first step is usually testing for antibody levels in the blood (IgG, IgA, IgM, and IgE). In some patients, one or more of these values will be dramatically below normal values, signaling a possible antibody deficiency disorder.

However, sometimes these values are normal or only slightly reduced in someone with an antibody deficiency disorder. It is often more effective to do testing of specific antibody responses.

This can be done by giving an individual one or more vaccines (such as for tetanus or pneumococcus). Before and after, the clinician uses blood tests to see whether the antibodies appropriately increase after the vaccine is given. For many antibody deficiency disorders, this normal antibody response is diminished or absent.

Other basic laboratory tests, like a complete blood count (CBC), can sometimes be helpful. Tests for lymphocytes and complement (other components of the immune system) can sometimes give relevant information.

However, definitive diagnosis also usually requires other unusual and specialized tests. Some type of genetic testing is usually needed for a definitive diagnosis.

Diagnosis of Specific Underlying Infections

If an active infection is present, this may require additional diagnostic tests to find the source of current infection. These will depend on the specific symptoms and clinical situation. For example, a blood culture might be needed to confirm a specific type of bacterial infection. Other tests, like chest X-ray, might also be needed.


Many patients with antibody deficiency diseases will also need antibody replacement therapy, to help prevent infections. This can be taken as a shot or through an intravenous line. Antibody replacement is given not just when a person is experiencing an infection, but long-term to help prevent future infections. 

For example, people with CVID who take antibody replacement therapy may not experience pneumonias as often. However, such therapy isn’t necessary for all patients with antibody deficiency diseases. For example, someone with a deficiency in IgA might not need such treatment. 

Many people with antibody deficiency diseases will also need other prophylactic treatments to help prevent infections. For example, this might mean taking an antibiotic like amoxicillin over the long-term (and not just when signs of an infection appear). This helps ensure that potential infections are treated quickly before they can take hold.

Hematopoietic stem cell transplantation (HSCT) is also a treatment option for some people with antibody deficiency diseases. In this treatment, a person’s original bone marrow cells (including immune cells like B cells) are killed off. The person is given donated normal stem cells that can be used to rebuild the immune system. 

Unlike these other options, HSCT can provide a definitive cure. However, it carries some major risks, and it isn’t an appropriate choice for every person. 

Additional treatments might be needed based on the specific type of antibody deficiency disorder and the specific symptoms that occur.

Treatment for Active Infections

Even with these preventative measures, infections may still sometimes happen. These need to be treated directly, such as with antiviral treatments for a viral infection or antibiotics for a bacterial infection. 


Because of better treatments, many people with more severe antibody deficiency disorders now do much better than they did in the past.

With proper diagnosis and treatment, these individuals are much less likely to die from complications from these disorders, such as from an infection or long-term lung damage. Now most individuals will be able to lead relatively normal lives. 

However, even with treatment, these individuals may still have a higher risk of certain health problems, like certain kinds of cancer. 


If you or someone in your family has been diagnosed with an antibody deficiency disorder, it may be helpful to speak with a genetic counselor. Not all these disorders have the same inheritance pattern.

But a genetic counselor can give you an idea of the risks that a future child might be born with an antibody deficiency disorder. Such a professional can also give good advice about whether testing for other family members might make sense. 

A Word From Verywell

Receiving a diagnosis of an antibody deficiency disorder can be overwhelming—there’s a lot to learn. However, if you’ve been experiencing repeated infections, it may actually be reassuring to know that there is an underlying cause. With proper medical care, you should be able to successfully manage your disease. 

10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. O'Keefe AW, Halbrich M, Ben-Shoshan M, McCusker C. Primary immunodeficiency for the primary care providerPaediatr Child Health. 2016;21(2):e10-e14. doi:10.1093/pch/21.2.e10

  2. McCusker C, Upton J, Warrington R. Primary immunodeficiency. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):61. doi:10.1186/s13223-018-0290-5

  3. Ameratunga R, Ahn Y, Steele R, Woon ST. Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthoodClin Exp Immunol. 2019;198(2):224-232. doi:10.1111/cei.13345

  4. Raje N, Dinakar C. Overview of immunodeficiency disordersImmunol Allergy Clin North Am. 2015;35(4):599-623. doi:10.1016/j.iac.2015.07.001

  5. Gernez Y, Baker MG, Maglione PJ. Humoral immunodeficiencies: conferred risk of infections and benefits of immunoglobulin replacement therapyTransfusion. 2018;58 Suppl 3(Suppl 3):3056-3064. doi:10.1111/trf.15020

  6. Swain S, Selmi C, Gershwin ME, Teuber SS. The clinical implications of selective IgA deficiency. J Transl Autoimmun. 2019;2:100025. doi:10.1016/j.jtauto.2019.100025

  7. Bazregari S, Azizi G, Tavakol M, et al. Evaluation of infectious and non-infectious complications in patients with primary immunodeficiencyCent Eur J Immunol. 2017;42(4):336-341. doi:10.5114/ceji.2017.72825

  8. Mortaz E, Tabarsi P, Mansouri D, et al. Cancers related to immunodeficiencies: update and perspectivesFront Immunol. 2016;7:365. doi:10.3389/fimmu.2016.00365

  9. Marciano BE, Holland SM. Primary immunodeficiency diseases: current and emerging therapeuticsFront Immunol. 2017;8:937. doi:10.3389/fimmu.2017.00937

  10. MedlinePlus. Common variable immune deficiency. May 2016.

By Ruth Jessen Hickman, MD
Ruth Jessen Hickman, MD, is a freelance medical and health writer and published book author.