Getting a diagnosis for primary immunodeficiency (PI), also called inborn errors of immunity (IEI), often starts with a blood test called a serology test.

Serology tests check your blood for antibodies, which are proteins made by your immune system. These tests alone can’t confirm PI, but they can give immunology experts important clues about why you may be getting sick more often than usual.

Continue reading to learn more about how serology blood tests can help diagnose PI and what the results might mean for you.

What Is Serology?

Serology is the study of antibodies and other substances in the clear part of your blood, called serum. Serology tests help doctors understand how well your immune system is working.

Your doctor may order a serology test to check for:

• A past infection caused by certain pathogens, such as bacteria or viruses
• Protection from a vaccine and whether you need another dose
• An immune deficiency
• An autoimmune disease, which happens when the immune system attacks the body’s own tissues

How Is a Serology Test Done?

A serology test is done like most routine blood tests. A small sample of blood is taken, usually from a vein in your arm, and sent to a lab. A technician looks for specific antibodies or other immune response markers.

It may take a few days or longer to get your results, depending on the type of test and the laboratory.

Serology Test Results

Serology test results can be reported in different ways:

• Quantitative — Shows the exact amount of an antibody in your blood
• Qualitative — Reports whether an antibody is present (positive), absent (negative), or unclear (indeterminate)
• Semiquantitative — Estimates how strong your antibodies are by measuring how they work at different dilutions (also called a titer)

The reporting format depends on the specific test and what the doctor needs to evaluate.

Use of Serology Tests To Help Diagnose Primary Immunodeficiency

Serology tests are often among the first laboratory tests ordered if you show signs of PI, such as:

• Recurrent infections
• Severe infections
• Unusual infections
• Need for intravenous (IV) antibiotics to treat a bacterial infection
• A family history of PI
• Poor growth or trouble gaining weight in children

These signs may mean your immune system isn’t working the way it should. Your primary care provider will likely refer you to an immunologist. This is a doctor who specializes in diagnosing and treating immune system disorders.

Serology tests are an essential part of this evaluation. They’re especially useful because the most common types of PI involve low levels of antibodies, though some PI conditions involve T cells, neutrophils (a type of white blood cell), complement, or immune dysregulation, where antibody levels may be normal.

Tests such as the following may be used to check different parts of the immune system:

• Complete blood count — Measures the number and types of blood cells
• Flow cytometry — Counts different types of immune cells
• T-cell function tests — Check how well T cells work
• Neutrophil function tests — Evaluate how well neutrophils work
• Complement deficiency tests — Measure the levels of special immune proteins called complement
• Genetic testing — Looks for genetic changes associated with PI

Your doctor will likely also do a physical examination to look for visible signs of illness. These may include swollen lymph nodes, rashes, or growth problems. Along with serology tests, these tests give doctors a clearer picture of how your immune system is working and help guide the treatment plan.

Serology Tests That Measure Antibody Levels

One common type of serology test is a quantitative antibody test. This test measures the amount of different antibodies (also called immunoglobulins) in your blood. It’s also called an immunoglobulin (Ig) blood test.

Doctors will measure the levels of different types of antibodies, including IgG, IgM, and IgA. In some cases, they’ll also measure IgE. They’ll compare your immunoglobulin levels to those of people in your age group who don’t have immune system problems.

What Do the Results Mean?

If your immunoglobulin levels are too low, you may have an antibody deficiency or a problem with your B cells. B cells are immune cells that make antibodies to help fight infections.

Types of PI linked to low immunoglobulin levels include:

• Common variable immunodeficiency (CVID)
• Selective IgA deficiency
• Congenital agammaglobulinemias

Sometimes, people with X-linked lymphoproliferative syndrome also have abnormal immunoglobulin levels. However, this condition mainly affects how the immune system is controlled.

Quantitative antibody tests alone can’t diagnose PI. Low immunoglobulin levels can also be caused by other health conditions, such as:

• Protein loss due to kidney or gut problems
• Some medications, including immunosuppressive therapies
• Some blood cancers or blood conditions

If your immunoglobulin levels are higher than normal, it might mean that you have a health condition, such as an infection, blood cancer, or liver disease.

Tests That Measure Antibody Production

In addition to measuring your antibody levels, doctors need to know how well your immune system makes antibodies. This is often done with an antibody response test.

To perform this test, your doctor will measure your antibody levels before and after giving you a vaccine. Vaccines work by training your immune system to make antibodies against a specific pathogen, such as a virus or bacterium that can cause illness.

Different vaccines activate different parts of the immune system. For example, the tetanus and diphtheria vaccine depends on T cells to trigger a response.

The pneumococcal vaccine may also trigger a T-cell response, depending on the type. Polysaccharide pneumococcal vaccines usually work without T cells, while conjugate versions rely on them.

You’ll have a blood test before the vaccine and another about four weeks later to check for changes in your antibody levels.

What Do the Results Mean?

In people with a healthy immune system, antibody levels should rise after a vaccine. If your levels don’t increase, it may mean that your immune system has trouble making certain antibodies.

Problems making antibodies may suggest that your B cells are not working properly. If results are abnormal, doctors may order flow cytometry to measure specific types of B cells. This test helps identify types of PI that cause a lack of B cells or problems with B cell development.

Tests That Check for Autoantibodies

Certain kinds of PI can cause the immune system to become overactive, leading to autoimmunity. This means the immune system makes autoantibodies, which attack healthy tissues in the body.

Serology tests can detect autoantibodies and check for autoimmune diseases. These tests can be helpful because up to 1 in 4 people with antibody deficiencies also have an autoimmune problem.

Autoimmunity is the main problem in some types of PI, including:

• Autoimmune polyendocrinopathy, candidiasis, ectodermal dysplasia
• Autoimmune lymphoproliferative syndrome
• Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome

Autoimmunity is also common in several other types of PI, such as:

• CVID
• Selective IgA deficiency
• Hyper IgM syndrome

What Do the Results Mean?

If you have autoantibodies, it can suggest that your immune system is attacking healthy tissues. Knowing the specific type of autoantibody you have can help doctors understand which tissues or organs are affected.

Talk to Your Healthcare Team

Blood tests are an important part of getting a PI diagnosis, but this process may take several years. Blood tests alone can’t diagnose PI, but they can give your healthcare team important clues about which part of the immune system may be affected. They can also help guide which additional tests you might need.

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